Overview

Throughout our efforts, we have consistently focused on integrating our project into society. Successfully embedding a project within the community requires a thoughtful and creative approach to proving its feasibility and responsibility. From the project's inception until the final stages before the wiki freeze, we continuously refined our work, guided by iGEM's Human Practice principles.

Throughout our activities, feedback from Human Practice played a crucial role in the following areas:

1. Discover the problem
2. Understand the problem
3. Design our product
4. Feasibility of implementing the project in real life
5. Project publicity and education

We, Testdaily-i-Beijing, are an iGEM team established in December, 2023. Initially, we were simply a group of high school students passionate about synthetic biology, without even access to a lab. Despite these challenges, we have adhered to the Human Practice principles of iGEM from the very start. Our Human Practice activities have focused on two key objectives:

• Engaging with a diverse range of stakeholders to exchange ideas.
• Reflecting on and enhancing our project based on lessons learned.

Through the first objective, we gained valuable insights by interacting with various stakeholders, including experts, companies, and the general public, and gathered feedback on our project.

In the second objective, we used these insights and feedback to refine and elevate the quality of our project through continuous iteration and improvement.

1 Discover the Problem

1.1 We Discovered through the Patient that Fracture Recovery is Very Slow and Painful

1.1.1 Interview Transcript

Dr. Puzhou Lei, Orthopedic Surgeon at the ShengJing Hospital of China Medical University

1.1.2 Interview Analysis

We first consulted Dr. Lei, the attending physician of the patient, to learn as comprehensively as possible about the causes of bone problems, the impact of bone problems on patients' lives, and the current prevalence of bone problems in children/adolescents. Dr. Lei has many years of rich clinical experience in orthopedics, so he may solve our problems very well.

We are very lucky to have an interview with Doctor Lei. Through our discussion, we discussed several significant insights about bone issues and their treatments. We learned that bone fractures and scoliosis emerged as major concerns in orthopedics. According to Doctor Lei, Fractures are typically caused by trauma, either through direct violence like accidents or falls, or indirect violence such as sports injuries. Scoliosis, on the other hand, can result from various causes including idiopathic, degenerative changes, or genetic conditions like Marfan syndrome. Notably, scoliosis is increasingly prevalent among the elderly due to degenerative changes, and among children, particularly teenage girls, often attributed to poor posture.

Takeaway:

We learned from the interview with Dr. Lei that bone fractures and scoliosis are major concerns in orthopedics. Fractures are typically caused by trauma, either from direct violence like accidents or falls, or indirect violence such as sports injuries. Scoliosis, on the other hand, can result from various causes, including idiopathic origins, degenerative changes, or genetic conditions like Marfan syndrome. Notably, scoliosis is increasingly prevalent among the elderly due to degenerative changes and among children, particularly teenage girls, often attributed to poor posture.

1.2 Questionnaire Survey on Bone Health/Bone Repair

1.2.1 Results

Question 1: Have you ever had a fracture or other bone problem?

Question 2: Do you often experience bone or joint pain?

Question 3: Do you know the correct sitting posture?

Question 4: Do you know what factors affect your bone health?

Question 5: How often do you exercise each week?

Question 6: How much calcium-containing food (such as cheese, yogurt, tofu, etc.) do you consume every day?

1.2.2 Analysis of Bone Health Challenges in Children in China

Bone injuries, scoliosis, and bone defects in children represent significant health challenges in China. These conditions, often resulting from falls and improper sitting postures, lead to structural damage, functional impairment, pain, inflammation, and restricted movement, significantly impacting the quality of life. Our team aims to understand the prevalence and severity of these bone issues and assess the general public’s awareness through a detailed questionnaire. The results of this survey will help us gain a deeper understanding of bone health in China and guide our next steps in addressing this issue and spreading awareness.

Our questionnaire consists of four parts: basic information, health habits, bone-related health history, and bone protection knowledge. All entries are recorded anonymously, protecting the respondents' information. The questionnaire is distributed through our team members’ social media accounts, our team social media, and at conferences like CCIC. As of July 23rd, 202 entries were collected and analyzed.

After graphing and analyzing the data, we found that the main responding population was between the ages of 13-18. Notably, 86.14% of the respondents had experienced bone fractures or other types of bone issues before (Figure 1), and 38.61% regularly feel pain in their bones or joints (Figure 2). Additionally, while most respondents possessed knowledge regarding bone health—with 72.77% answering yes when asked if they know the correct posture (Figure 3) and a varied high proportion understanding different factors that affect bone health (Figure 4)—there are still gaps in education regarding bone health. This is especially prevalent in areas related to food consumption and exercise habits. Out of the 202 respondents, 50.49% rarely exercise or only exercise once or twice per week (Figure 5), and 77.72% rarely or never consume foods rich in calcium such as cheese and tofu (Figure 6).

Takeaway:

The survey results indicate that bone health issues are prevalent among Chinese children, with a significant number experiencing bone fractures and regular pain. While there is a general awareness of correct postures and factors affecting bone health, there are critical gaps in exercise routines and dietary habits that need to be addressed. These findings underscore the need for better awareness amongst the public in actions to prevent bone-related health issues. Our team will use these insights to better inform our project and take more actions to spread awareness on this issue.

2 Understand the Problem

2.1 Understand the Bone Recovery Process and the Key Element: Cell Factor

2.1.1 Interview Transcript

Dr. Puzhou Lei, Orthopedic Surgeon at the ShengJing Hospital of China Medical University

2.1.2 Interview Analysis

In order to understand the bone recovery process and the key elements involved, we found Dr. Lei . He told us the current treatments for these conditions include a variety of methods such as external and internal fixation and bone grafts. Each treatment method presents its challenges, including limited bone volume for autografts and potential immune rejection for allografts. While artificial bone materials show promise, they also face issues such as poor biocompatibility and infection risks. Therefore, we asked him to give us a guide on what qualities an ideal bone should have. He listed several elements: absolute biocompatibility to prevent immune rejection; sufficient mechanical strength to support the bone structure; controlled release of therapeutic agents; and a degradation rate that matches the rate of bone tissue regeneration. Additionally, the inclusion of cell factors is crucial for promoting osteogenesis, as they play a significant role in signaling and regulating the bone formation process. In fact, cell factors are the most important element in bone regeneration.

Our team had the opportunity to consult with Dr. Lei of the ShengJing Hospital, specializing in orthopedic surgery, on the current severity of bone related issues in China, namely bone injury and trauma and scoliosis. Through the interview, we were able to understand his opinions on the currently available methods of bone injury repairment and become more aware of the critical issues presented by current bone repair methods and materials to orthopedic surgeons in China.

During the interview, we discussed treatment methods of both external fixation utilizing metal screws and wires to fix an external fixator in place to the targeted bone, as well as internal fixation methods using metal nails and rods, grafting methods, or synthetic bone and bone tissue material. Dr. Lei expressed overall satisfaction with the current available methods of bone repair such as grafting or transplanting and using metal rods and materials to stabilize bone structures. However, Dr. Lei expressed further pleasure to the method of autografting, where there is a high percentage biocompatibility and lower risk of both infection and rejection of the bone or bone tissue for the patient, as the graft comes from the patient themself. However, Dr. Lei expressed concern for the limited supply of suitable bone material available in a patient’s body to be surgically transplanted as there are limits to what tissues and materials can be removed and transplanted and what can not be touched. For example, Dr. Lei explained that compact, or cortical bone tissue is not used in transplants or grafts as it ends in poor results and negatively impacts the health of many patients. Dr. Lei stated that fresh spongy bone tissue is more commonly used for bone repair as it is more reliable and safe, and is organized to provide maximum support and strength to the bone. However, due to limited, spongy bone is only used to treat smaller bone injuries. Surgeons also choose to use allogeneic grafts for patients, but are often faced with higher risks of both infection and rejection of the bone or tissue transplanted. Patients can also be faced with the problem of being unable to find a matching donor in the time span available. Therefore, due to limited supply of suitable bone and tissue materials, many surgeons in China often have to turn to different methods such as the use of synthetic materials to treat patients due to the severity and size of their bone injuries.

When discussing synthetic bone graft materials with Dr. Lei, he presented us with many of the issues surgeons are posed with when using artificial materials. Dr. Lei expressed deep concern for the biocompatibility such as blood and cell factor release and sterility of synthetic materials. If not compatible with the patient, chances of the patient’s body rejecting the synthetic tissue or bone are high and the risk of having to operate on the patient again to remove the synthetic material poses severe threats to the patient’s health. Further, if the synthetic material is not produced under and maintained under sterile conditions, the patient faces higher risks of infection after surgery. Synthetic materials also nowhere nearly promote the growth of new bone material and tissue as natural materials from transplants would.

Through the interview, Dr. Lei discussed his hopes for synthetic bone materials in the future to be developed to have high biocompatibility, low risk of infection, higher mechanical strength and support of bone structure, the controlled release of drug and cell factors, and for the degradation rate of the material to match that of the natural bone tissue regeneration rate. Dr.Lei highly emphasized the importance of degradation rate to himself, stating that he wishes for the material to degrade at the same rate as the new bone tissue is regenerated, rather than the synthetic material dissolving before it can even be replaced with new bone tissue, and that the rate of degradation can match the rate of regeneration, as synthetic materials can never outcompete the benefits of natural bone material. We also took cost and blood loss during surgery procedures into consideration and aim to create a material which can be available to anyone who needs the aid and create minimal negative impact on the patient both during and after surgery.

Takeaway:

Through discussion with Dr. Lei, we realized what issues many surgeons are presented with when working with synthetic materials in orthopedic surgery. Therefore, after consulting with Dr. Lei, our team decided to focus on the main concerns presented by the doctor. We were further empowered to create a cost effective and surgery efficient synthetic bone material promoting higher biocompatibility, lower risk of infection, provide support and encourage the regeneration of new bone tissue while matching the degradation rate of the artificial material to the regeneration rate of the new bone to be utilized in bone repair to counter the severe bone injury issues facing China today.

2.2 The Most Critical Cell Factors in Osteogenesis are BMPs

2.2.1 Interview Transcript

2.2.2 Interview Analysis

During the interview with Professor Huo, we gained a deeper understanding of the role of BMP4 in promoting osteogenesis. Professor Huo explained that while BMP proteins can significantly accelerate bone formation, their high cost and limited activity present major challenges in research. Due to the complexity of BMP proteins, which contain multiple disulfide bonds, large-scale expression systems are typically required for production. However, this often leads to lower purity and reduced biological activity. Professor Huo suggested that the team could overcome these issues by producing BMP4 in-house.

Takeaway:

Through this interview, the team identified the critical role of BMP4 and the technical challenges in its production. Ultimately, the team decided to follow Professor Huo’s advice and set up an in-house system to produce BMP4, aiming to reduce costs and enhance its activity. The key is finding a solution that improves production efficiency while ensuring both purity and activity of the product.

2.3 Dr. Jin Suggested that We Use More Cell Factors

2.3.1 Interview Transcript

Dr. Jin, synthetic biology expert at Tsinghua University

2.3.2 Interview Analysis

During our interview with Dr. Jin, he suggested a strategy to enhance bone healing by using multiple cellular factors. Dr. Jin explained that the bone healing process can be divided into three key phases, and for each phase, we could select a specific cellular factor to support and optimize regeneration. However, he also warned us about the risks of using too many cellular factors simultaneously. Overloading the system could lead to an imbalance, which might trigger severe side effects and interfere with the healing process.

Dr. Jin advised us to be more selective in choosing the cellular factors, ensuring that we focus on the most essential ones for each phase of healing. His concern was that adding too many factors at once could cause adverse reactions or overstimulation, which could be counterproductive.

After carefully considering Dr. Jin’s advice, we decided to reduce the number of cellular factors we are using. This approach will allow us to maintain better control over the bone healing process and minimize the risk of complications.

Takeaway:

The key takeaway is to balance innovation with caution. Overloading the system with too many cellular factors can lead to negative effects, so it’s important to carefully select and manage the factors at each phase to maximize healing while minimizing risks.

2.4 Confirming the Necessity of Two Cell Factors

2.4.1 Interview Transcript

2.4.2 Interview Analysis

In our interview with Dr. Lei, we sought confirmation about our approach to selecting cellular factors for bone healing. Dr. Lei explained that the first phase of healing—the inflammatory phase—does not necessarily require the use of cellular factors. Instead, more stable chemical substitutes, such as anti-inflammatory drugs, could be more effective at controlling inflammation and creating a favorable environment for healing.

Dr. Lei pointed out that introducing cellular factors like TGF-β during the early inflammatory phase could trigger unnecessary complications, such as excessive immune responses. Instead, we could focus on using anti-inflammatory medications to manage this phase, saving cellular factors like VEGF and BMP4 for the later stages of repair and remodeling, where they can have a more targeted and beneficial impact. Dr. Lei emphasized that using fewer cellular factors in the early phase could also simplify the treatment process, reducing the risk of side effects.

After this discussion, we realized that our original plan to introduce TGF-β early on might not be the best course of action. Based on Dr. Lei’s input, we decided to remove TGF-β from our inflammatory phase strategy and instead use a combination of anti-inflammatory drugs during this stage. For the subsequent phases, we confirmed our decision to focus on VEGF and BMP4 as key factors to drive bone formation and remodeling.

After discussing with Dr. Lei, we concluded that using chemical substitutes like anti-inflammatory drugs in the early phase of healing is more effective than introducing cellular factors. We will save cellular factors like VEGF and BMP4 for the later stages to maximize their effectiveness in bone repair.

Takeaway:

The key takeaway from this interview is that not all phases of bone healing require cellular factors. Inflammatory control can be better managed with anti-inflammatory drugs, allowing cellular factors to be used more strategically in later stages for optimal results.

3 Design our Product

3.1 Bone Repair Materials

3.1.1 Interview Transcript

3.1.2 Interview Analysis

In our interview with Professor Huo, we discussed the different types of bone repair materials and their effectiveness. Professor Huo explained that bone repair materials generally fall into three categories: autografts (from the patient’s own body), allografts (from a donor of the same species), and synthetic materials. He pointed out that autografts and allografts are difficult to obtain in large quantities and present certain risks, such as immune rejection and limited availability. Due to these challenges, the focus in the field has shifted toward the development of synthetic materials for bone repair.

Professor Huo emphasized that the most promising synthetic materials are those that incorporate biologically active components, such as cellular factors. These bioactive materials can actively promote bone regeneration and healing by mimicking the body's natural processes. By integrating cellular factors like BMPs (Bone Morphogenetic Proteins) into synthetic scaffolds, we can create materials that not only support the bone structure but also enhance the biological healing process.

After hearing his insights, we realized that our product development should prioritize synthetic materials combined with cellular factors. This approach offers the best of both worlds: the stability and availability of synthetic materials, along with the biological activity needed to accelerate healing.

Based on our conversation with Professor Huo, we decided to focus on developing synthetic bone repair materials that integrate bioactive components like cellular factors. This strategy will allow us to create materials that are both readily available and highly effective at promoting bone regeneration.

Takeaway:

The key takeaway is that while natural bone grafts are limited, synthetic materials that incorporate bioactive components, such as cellular factors, hold the most promise for effective bone repair. These materials offer greater availability and the ability to actively enhance healing.

3.2 Understand the Artificial Bone Repair Materials on the Market

3.2.1 Interview Transcript

Doctor Ding From Benq Hospital Orthopedics Department

3.2.2 Interview Analysis

After proposing the idea of creating a new bone repair material, we conducted thorough research on the current bone repair products available on the market and the common bone-related issues faced by people in daily life. To deepen our understanding, we reached out to Dr. Ding, a highly experienced orthopedic clinician with 16 years of clinical practice and a doctoral degree in the field. Our interview with him provided key insights relevant to both the orthopedic field and our project.

Dr. Ding shared that many of his patients suffer from pain and mobility problems due to bone fractures, joint issues, or degenerative diseases. He emphasized how these conditions often severely impact the patients' quality of life. According to him, a key challenge in treating such conditions is the time it takes for bones to heal, especially in elderly patients or those with complex fractures. He pointed out that an ideal bone repair material would not only support the bone structure but also actively promote faster regeneration.

We presented our project, which uses BMP4 and VEGF to enable controlled cytokine release for enhanced bone healing. Dr. Ding appreciated our approach but highlighted several important challenges in translating the research into clinical applications. He mentioned the need for pre-clinical testing, starting with animal studies to assess safety and efficacy, followed by regulatory approvals to ensure that the material is non-toxic, biocompatible, and effective. These steps are crucial to make sure the material is viable for real-world medical use.

Toward the end of the interview, we discussed the orthopedic materials currently used in clinical practice. Dr. Ding explained that most existing materials are either synthetic or derived from donor tissues, both of which have limitations. Synthetic materials often lack bioactivity, while donor tissues carry the risk of immune rejection and have limited availability. He pointed out that combining the stability of synthetic materials with the biological activity of growth factors like BMP4 and VEGF could be a game-changer, provided the material is easily degradable, non-toxic, and supports the body’s natural healing process.

Conclusion:

From our conversation with Dr. Ding, we learned that the future of bone repair lies in the development of bioactive, biocompatible materials. Our next steps will involve adjusting our product to better meet clinical needs, conducting pre-clinical testing to ensure safety and efficacy, and preparing for regulatory approval to bring the product to real-world use.

Takeaway:

The interview underscored the importance of creating a material that balances structural support with biological activity. Moving forward, our focus will be on minimizing risks, ensuring biocompatibility, and completing the necessary tests to ensure that our material can successfully integrate into clinical practice.

3.3 Identification of Collagen as an Ideal Matrix for Bone Repair

3.3.1 Interview Transcript

3.3.2 Interview Analysis

Our team had the special opportunity to consult with Dr. Lei of the ShengJing Hospital, specializing in orthopedic surgery, on the current severity of bone related issues in China, namely bone injury and trauma and scoliosis. Through the interview, we were able to understand Dr. Lei’s opinions on the currently available methods of bone injury repairment and become more aware of the critical issues that current bone repair methods and materials present to orthopedic surgeons in China.

During the interview, we discussed treatment methods of both external fixation methods utilizing metal screws and wires to fix an external fixator in place to the targeted bone, as well as internal fixation methods using metal nails and rods, grafting, or synthetic bone and bone tissue material. Dr. Lei expressed overall satisfaction with the current available methods of bone repair such as grafting or transplanting and using metal rods and materials to stabilize bone structures. Dr. Lei expressed further pleasure to the method of autografting, due to its high percentage of biocompatibility and low risk of both infection and rejection of the bone or bone tissue from the patient’s body. As the grafted material is taken from the patient’s own body, the presence of the material will be natural to the system and offer much lower risks of complications such as rejection and infection. However, Dr. Lei expressed concern over the issue of the limited supply of suitable bone material available in a patient’s body to be surgically transplanted. The concern over limited supply of transplantable bone material is due to the restrictions regarding what tissues and materials can and cannot be surgically removed and transplanted. For example, Dr. Lei explained that compact, or cortical bone tissue is unsuitable in transplants and grafts, as it produces poor results and often maliciously impacts the health of patients. Instead, Dr. Lei stated that fresh spongy bone tissue is more prevalently used for bone repair by reason of its reliable and safe nature. The spongy bone provides stability as its structure is constructed to provide maximum support and strength to the bone. However, due to limited supplies available in the human body, spongy bone is only used to treat smaller bone injuries, leaving larger injuries at a disadvantage and loss of reliable bone repair methods. Only 20 percent of the human skeleton system is constructed of cancellous, or spongy bone, and not all are suitable for repairing bone trauma injuries, often causing surgeons to result to other methods. Surgeons also choose to use allogeneic grafts for patients, but patients are often faced with higher risks of both infection and rejection of the bone or tissue transplanted. Patients can also be faced with the problem of being unable to find a matching donor in the time span available. Therefore, due to limited supply of suitable bone and tissue materials, many surgeons in China often must turn to different methods, such as the use of synthetic materials, to treat patients based on the severity and size of their bone injuries.

When discussing synthetic bone graft materials with Dr. Lei, he presented us with many of the issues surgeons are posed with when using artificial materials. Dr. Lei expressed deep concern for the biocompatibility of the synthetic bone materials or tissues with the patients. Examples brought up include biological factors such as blood and cell factor release. If not biocompatible with the patient, chances of the patient’s body rejecting the synthetic tissue or bone are high, creating risks of having to operate on the patient again to remove the synthetic material. Hence, posing severe threats to the patient’s health. Further, Dr. Lei pointed out the issue regarding the questionable guarantee of the sterility of synthetic materials. If the synthetic materials are not produced and maintained under sterile conditions, the patient will face dangerous higher risks of infection post-surgery. Furthermore, synthetic materials nowhere nearly promote the growth and regeneration of new bone material and tissue as quickly and well as natural materials from transplants would.

Through the interview, Dr. Lei discussed his hopes for future synthetic bone materials to be developed to possess high biocompatibility, low risk of infection, higher mechanical strength and support of bone structure, ability for the controlled release of drug and cell factors, and for the degradation rate of the material to match that of the natural bone tissue regeneration rate. Additionally, Dr.Lei highly emphasized the importance of the degradation rate, highlighting his wishes for the synthetic material to degrade at the same rate as the new bone tissue is regenerated, rather than for the synthetic material to dissolve before it can even be replaced with new, naturally regenerated bone tissue. Dr. Lei expressed his hopes for the synthetic material rate of degradation to match the rate of natural regeneration, so that regenerated natural bone and bone tissue can take the place of the artificial material, as the foreign synthetic materials will never be able to outcompete the benefits of bone material natural to the body. We also took cost and blood loss during surgery procedures into consideration and aim to create a material which can be available to anyone who needs the aid and create minimal negative impact on the patient both during and after surgery.

Hence, through considerations of issues presented by Dr. Lei, our team decided to focus in on the limited natural resources of spongy bone tissue threatening orthopedic surgeons throughout the world and on addressing the dangers and problems presented by Dr. Lei on the use of artificial synthetic bone materials for bone repair surgery. Our team brainstormed the use of two different types of synthetic materials to be used to engineer artificial spongy bone: chitosan and collagen sponge. We presented both ideas to Dr. Lei and questioned him on which he believed would be the better option, to which he responded with great approval of the use of collagen sponge. Hence, in accordance with Dr. Lei, our team decided to investigate further into the use of collagen sponge as an artificial spongy bone material.

First, due to collagen sponges’ natural characteristic of being compacted with growth factors which induce bone tissue regeneration, such as BMPs and fibroblast growth factors (FGFs), collagen sponges have been commonly used before in clinical practices. Collagen is also capable of promoting the growth and angiogenesis of vascular endothelial cells to provide the necessary blood supply and nutrients needed to regenerate new bone tissue. Furthermore, collagen sponge contains hemostatic agents which produce a decrease in blood loss by activating platelets and a natural coagulation pathway. Therefore, leading to the use of collagen sponge in many clinical practices as an absorbable blood stopping material. However, with both hemostatic and bone tissue regenerative properties possessed by collagen sponges, the door to the greater incorporation of collagen sponges in orthopedic clinics is wide open to exploration. Our team decided to take the step into the door to propose and investigate the integration of collagen sponges into orthopedic surgery, supported with Dr. Lei’s approval.

The use of collagen sponge would provide many benefits to both doctors and patients alike. First, regarding biocompatibility, as a main structural protein naturally present throughout each human’s body, the percentage of biocompatibility of collagen sponge with patient’s bodies is quite high. In aspects of biodegradability, collagen can be degraded into molecules by enzymes in the human body. The degraded collagen molecules is then able to be eventually absorbed and utilized by the body, to allow for patients to avoid the need for a second surgery to remove the collagen sponge material. As collagen degrades through natural processes, it makes room for the growth of new bone tissue. Hence, addressing the issue regarding biodegradation brought up by Dr. Lei as well as providing convenience and lowering costs to patients from reducing the need of additional surgeries. Furthermore, collagen sponge would provide the mechanical strength and support as natural spongy bone would for bone structure. Collagen used to construct collagen sponges has excellent mechanical strength and elasticity properties. Hence, allowing for it to provide the sufficient support and stability to bone structure when conducting bone repair. Collagen sponge also has low immunogenicity to provide low risks of infection. Due to the high conservatism of collagen, it is harder to cause an immune response in the body due to its high conservatism and low immunogenicity. Lastly, the collagen constructing collagen sponges are easy to process, sterilize, and load. Collagen can also be processed into a variety of methods to apply to and meet different types of scenarios requiring different application requirements. Hence, creating greater ease and convenience to doctors. The Through these benefits, not only would collagen sponges take a step towards resolving the limitation of natural resources facing doctors, but it also further provides convenience and greater reliability to both doctors and patients alike. Hence, our team has chosen to take a direction into studying the use of collagen sponge regarding orthopedic surgery.

Takeaway:

We critically selected collagen sponge as the matrix for cytokines for the following reasons.

Through discussion with Dr. Lei, we realized what issues many surgeons are presented with when working with synthetic materials in orthopedic surgery today. After consulting with Dr. Lei, our team decided to focus on the main concerns over synthetic bone materials, presented by the doctor. We were empowered to create a cost effective and surgery efficient synthetic bone material promoting higher biocompatibility, decreasing risk of infection, promoting bone support, and encouraging the regeneration of new bone tissue while matching the degradation rate of the artificial material to the regeneration rate of the new bone, to be utilized in bone repair to counter the severe bone injury issues facing China today. Hence, leading us to the potential solution of collagen sponges, which counter the shortage of spongy bone available for transplant, and provide great perks to doctors and patients both during and post-surgery.

Dr. Lei’s insights confirmed that while autografts remain the best option for bone repair, their limited availability makes synthetic materials necessary in many cases. He emphasized that collagen sponge offers significant advantages over other synthetic materials, particularly due to its high biocompatibility, ability to promote bone regeneration, and controlled biodegradation. Moving forward, we will focus on optimizing the mechanical strength and degradation rate of the collagen sponge to ensure it provides effective support throughout the healing process. Additionally, we’ll consider how to scale up production to make this material more accessible and cost-effective for clinical use.

3.4 Explore Ways to Achieve Sustained Release of Cell Factors

3.4.1 Interview Transcript

Dr. Jin, synthetic biology expert at Tsinghua University

3.4.2 Interview Analysis

In our interview with Dr. Jin, we explored possible methods to achieve the sustained release of cellular factors for our project. Dr. Jin provided us with two primary approaches. The first approach involved chemically modifying the cellular factors so that they can bind to the surface of materials like collagen or other scaffolds. He suggested that we could achieve this binding using specific chemical agents, such as NHS-EDC, which would allow the cellular factors to adhere to the scaffold material and release gradually over time as the scaffold degrades. Dr. Jin explained that the key advantage of this method is that by tethering the cellular factors to a stable scaffold, the release rate of the factors can be better controlled, resulting in a more sustained effect.

The second approach Dr. Jin suggested was creating a composite material by embedding the cellular factors directly into the scaffold during its fabrication. In this method, the cellular factors would be mixed with the base material, such as collagen or a synthetic polymer, during the production of the scaffold. As the scaffold naturally degrades in the body, the embedded factors would be released gradually. This method could allow for an even distribution of cellular factors throughout the scaffold, ensuring consistent release as the material breaks down.

Dr. Jin was particularly concerned about the complexity of chemically modifying cellular factors. He noted that while chemical conjugation might allow for more precise control over factor release, it could potentially affect the biological activity of the cellular factors, making them less effective. There is a risk that modifying the cellular factors with chemical groups could disrupt their ability to interact with their target cells, reducing their overall impact. He also explained that the release could be less predictable if the chemical bonds degrade at inconsistent rates.

On the other hand, Dr. Jin recommended embedding the cellular factors directly into a composite scaffold. He felt that this approach would be more straightforward to implement and would maintain the integrity of the cellular factors. By incorporating the factors into the scaffold material itself, the release would occur naturally as the scaffold breaks down, minimizing the risk of interfering with the biological activity of the factors.

After discussing the pros and cons of each method, we decided that embedding the cellular factors into a composite scaffold would be the best option for our project. It offers a more reliable release mechanism and reduces the risk of altering the cellular factors' activity through chemical modifications. This approach would also simplify the production process while ensuring that the cellular factors are gradually and consistently released over time.

Takeaway:

Based on Dr. Jin’s insights, we concluded that embedding cellular factors into a composite scaffold is the optimal method for achieving sustained release. This approach ensures the biological integrity of the factors and allows for a gradual release as the scaffold degrades, without the need for complex chemical modifications. We will proceed with this method to optimize our bone repair material and achieve a more controlled and effective healing process.

The key takeaway from our interview with Dr. Jin is that while chemically modifying cellular factors offers precise control over release, it also carries the risk of reducing their effectiveness. Embedding the factors into a composite scaffold is a more straightforward and reliable approach that preserves the biological function of the factors and ensures their gradual release. This method aligns well with our project’s goals and will help us develop a more efficient bone repair material.

3.5 Hard Material Outside

3.5.1 Interview Transcript

3.5.2 Interview Analysis

During our interview with Professor Huo, we discussed the challenges of designing bone repair materials that can be used in specific medical situations requiring both bioactivity and structural support. While the internal parts of the scaffold need to focus on promoting bone regeneration through bioactive materials like collagen and cellular factors, Professor Huo highlighted the importance of incorporating rigid materials for certain applications, especially in areas like spinal fusion or large bones where mechanical support is crucial.

He pointed out that in procedures like spinal fusion, relying solely on soft materials such as collagen or chitosan could compromise the scaffold’s ability to maintain structural integrity during the healing process. For example, when fusing two parts of the vertebrae, a rigid material is required to hold them in place. Without this, the scaffold could collapse under the body’s weight, resulting in failed bone healing or deformities.

Professor Huo recommended using a material like PEEK (Polyetheretherketone) for the external structure of the scaffold. He explained that PEEK is known for its strength, durability, and biocompatibility, making it an ideal choice for providing the necessary mechanical support. PEEK is also radiolucent, meaning it doesn't interfere with imaging scans like X-rays or MRIs, which is a major advantage in post-surgical monitoring. Additionally, PEEK is a material that many surgeons are already familiar with and comfortable using in practice, especially in orthopedic and spinal surgeries. This familiarity makes it easier for medical teams to adopt the material without requiring additional training or specialized tools.

Professor Huo further explained that using PEEK alongside bioactive materials creates a hybrid scaffold that offers both the biological benefits needed for bone regeneration and the mechanical stability necessary for successful healing. The rigid parts made from PEEK would provide structural support in areas under mechanical stress, while the internal soft components like collagen would promote bone tissue growth. This combination would allow for better outcomes in procedures requiring both strength and biological activity, such as in large bone fractures or spinal surgeries.

We also discussed the fact that PEEK is easy to process and shape, which makes it adaptable to various scaffold designs. This versatility ensures that we can customize the scaffold depending on the specific requirements of the surgery or the bone defect. For example, we could design thicker PEEK layers in high-stress areas, while keeping the bioactive layers thin to maximize bone regeneration.

After considering all of Professor Huo's input, we realized that integrating a rigid material like PEEK into our scaffold design would greatly improve the mechanical stability of our bone repair product. By combining bioactive materials for regeneration with the strength of PEEK, we can address a wider range of bone injuries, particularly those requiring additional structural support.

Takeaway:

Based on our discussion with Professor Huo, we concluded that using PEEK as the external hard material for our bone repair scaffolds is the best approach. This will allow us to balance the biological benefits of collagen and cellular factors with the mechanical support needed in high-stress areas like the spine or large bones. Incorporating PEEK will ensure that our scaffold is both strong and bioactive, optimizing the healing process.. The key takeaway from our interview with Professor Huo is that bioactive materials alone are not sufficient for bone repair in areas requiring structural support. By integrating a rigid material like PEEK into the scaffold, we can ensure both stability and regeneration, providing a more comprehensive solution for bone injuries that need mechanical strength alongside biological healing.

3.6 Product Design Conclusion

Our product design has taken into account both the macro and micro aspects of bone repair, carefully integrating different key components to ensure both functionality and biocompatibility. The core of our product combines fusion proteins, collagen sponge, and a PEEK (Polyetheretherketone) outer layer. Each of these components plays a crucial role in addressing specific needs in bone repair.

Firstly, the fusion proteins incorporated into our design are essential for promoting osteogenesis (bone growth). These proteins help accelerate the regeneration process by stimulating the body's natural bone-building mechanisms, such as cellular differentiation and matrix formation. By embedding these proteins within the scaffold, we aim to ensure a controlled and sustained release, optimizing the healing process over time.

Secondly, the collagen sponge serves as the bioactive scaffold that supports tissue regeneration. Collagen is a well-known biomaterial due to its high biocompatibility and ability to promote cellular attachment and proliferation. By using collagen as the core of the scaffold, we can provide a matrix that encourages new bone formation while being naturally absorbed by the body. This eliminates the need for a secondary surgery to remove the material, reducing patient risk and recovery time.

Thirdly, we have chosen PEEK as the external hard shell of the scaffold, which addresses the need for mechanical strength and stability in areas subjected to high stress, such as the spine or large bone fractures. PEEK is an advanced biomaterial that is already widely used in clinical settings due to its superior mechanical properties, durability, and radiolucency, allowing doctors to monitor bone healing progress through X-rays or MRIs without interference. Its proven track record in medical applications ensures that it can withstand the physical demands placed on it, while still being safe for long-term implantation in the body.

Both the collagen sponge and PEEK outer layer are well-established products in the medical field, with extensive research backing their safety and efficacy. This gives us a strong foundation to build on as we further develop our product for clinical use. By leveraging these materials, we can ensure that our scaffold is both biocompatible and robust, providing the necessary support during bone healing while maintaining the biological environment required for tissue regeneration.

As we move forward, our primary focus will be on refining the expression and purification of the fusion proteins. This is a critical area of research and development, as the effectiveness of the product hinges on the proteins being delivered in their most active and purest form. Ensuring consistent and high-quality protein production will be essential to the overall success of the bone repair scaffold.

By continuing to optimize the integration of these components, we aim to create a product that not only supports bone regeneration but also ensures long-term success in clinical settings. Our goal is to provide a reliable, efficient, and safe solution for patients suffering from bone injuries, offering them a faster recovery with fewer complications.

4 Project Progress

4.1 Protein Expression & Interaction Issues

4.1.1 Interview Transcript

Dr. Jin, synthetic biology expert at Tsinghua University

4.1.2 Interview Analysis

After learning some basic principles about protein construction and interaction, we are honored to have Dr. Jin, an expert on fusion proteins from Tsinghua University. Dr. Jin introduced us to the construction methods of fusion proteins, including seamless cloning and enzyme-cut linking, and discussed their advantages and disadvantages. For example, seamless cloning has simple operation steps but high requirements for the design of primers; The accuracy of the enzyme ligand is very high, but the cost is high. Dr. Jin also stressed the need to design the sequence of binding proteins so that the fusion proteins are released sequentially because different proteins have different binding affinities. Dr. Jin also introduced us to the mechanism of protein and collagen binding and how to verify the function of fusion proteins through experiments at the macro and micro levels, both at the cellular and animal levels. From our talk, we also learned about the use of CCK-8 and MTT to characterize the biological activity of proteins, the use of ELISA to observe target proteins, and the use of SPR to evaluate the binding force of proteins and their respective strengths and weaknesses. For example, SPR is intuitive but expensive; The operation of ELISA is relatively simple but does not yield dynamic data.

Takeaway:

After discussions with Dr. Jin, we realized that there are many different approaches to achieving protein fusion and protein interaction. Our next step is to refine our experimental steps based on his suggestions, with a focus on evaluating the feasibility of each of the different approaches.

5 Project Implementation

5.1 Feasibility of Large-Scale Production

5.1.1 Interview Transcript

5.1.2 Interview Analysis

To explore the feasibility of mass-producing our fusion proteins, we visited Sangon Biotech (Shanghai) Co., Ltd., where we had the opportunity to consult with Dr. Liu, the company's R&D director. During the interview, we aimed to understand the key steps involved in large-scale protein production and the specific challenges that come with each stage. Dr. Liu provided invaluable insights into the process, particularly highlighting the most critical and costly phase—protein purification.

Dr. Liu explained that the production of fusion proteins begins with a well-established protocol for protein expression. This typically involves engineering host cells, such as E. coli or mammalian cells, to express the desired protein. While the initial steps of expressing the protein in these host cells are relatively efficient and scalable, the true challenge lies in the downstream processes, specifically purification. He emphasized that as production scales up, maintaining the purity and activity of the protein becomes significantly more difficult and expensive.

Dr. Liu explained that purification involves multiple steps, including cell lysis, centrifugation, and a series of chromatographic techniques to isolate the fusion protein from other cellular components. He noted that while techniques like affinity chromatography are effective for achieving high levels of purity, they can also be prohibitively expensive when applied on a large scale. Furthermore, maintaining the structural integrity and biological activity of the protein throughout these steps requires highly controlled conditions, adding another layer of complexity and cost.

One of the major bottlenecks Dr. Liu discussed was the balance between yield and purity. Increasing the yield of protein production often leads to higher levels of impurities, which in turn increases the burden on the purification process. This creates a significant cost challenge, as scaling up the purification phase can sometimes represent the largest portion of overall production costs. He advised that any cost-effective strategy would need to optimize both the yield from the host cells and the efficiency of the purification steps.

Dr. Liu also emphasized the importance of considering regulatory standards when producing proteins for clinical use. He mentioned that scaling up production is not just about the technical process; it also involves complying with Good Manufacturing Practices (GMP) to ensure the protein is safe, effective, and consistent across batches. This adds another layer of complexity, as production facilities need to be certified, and quality control becomes even more stringent at larger scales.

At the conclusion of our meeting, Dr. Liu suggested that we should focus on developing a streamlined purification process that balances cost with purity. He advised that we explore potential improvements in both the upstream (expression) and downstream (purification) stages to optimize efficiency without compromising the quality of the final product. Additionally, he recommended that we begin by conducting small-scale pilot runs to refine the process before moving into full-scale production.

Takeaway:

Based on our discussion with Dr. Liu, it is clear that the protein purification phase is both the most technically challenging and the most expensive part of the production process. While protein expression can be scaled up relatively easily, maintaining purity and biological activity at a large scale presents significant hurdles. To move forward, we will need to develop a more efficient purification strategy and consider small-scale tests to optimize both yield and cost-effectiveness before full-scale production.

The key takeaway from our meeting with Dr. Liu is that protein purification, while essential for ensuring product quality, represents the largest cost in large-scale production. By focusing on improving both expression yields and purification efficiency, we can reduce costs and improve feasibility for large-scale production. Additionally, compliance with regulatory standards is critical for ensuring that the product is safe and viable for clinical use.

5.2 Large-Scale Protein Purification

5.2.1 Interview Transcript

Yezhou, a synthetic biology expert from Dalian University of Technology, has extensive experience in mass production of proteins and enzymes

5.2.2 Interview Analysis

After performing an extensive research, we are honored to invite Dr. Ye, an expert in protein purification to give us some professional advice . Dr. Ye guided us through the intricacies of protein purification, emphasizing the importance of adhering to Good Manufacturing Practices (GMP) and international standards. She elaborated on the necessity of using medical-grade raw materials and maintaining stringent quality control throughout the purification process. Professor Ye also gave us instructions on the financial issues related. She told us the price of some materials and equipments and provided us with a potential cost we might reach. Besides, we learned that initial lab optimization might helps reducing costs.

Dr. Ye highlighted the importance of choosing the appropriate analysis medium and the critical steps in achieving high purity levels, such as exceeding 95% for antibodies and recombinant proteins, and even higher for therapeutic or diagnostic purposes.From our conversation, we learned that methods like ion exchange and gel filtration chromatography are pivotal in reaching medical standards. Dr. Ye explained that our initial purification might achieve 70-80% purity, but further steps like ion exchange and gel filtration are necessary in order to reach the required medical-grade purity. She also told us about the pros and cons of each method, noting that while ion exchange is costlier, it handles larger sample volumes and can be finely tuned for optimal results. Gel filtration is simpler and gentler, making it suitable for sensitive proteins but might require longer processing times and careful control of column conditions.

Takeaway:

Following our discussion with Dr. Ye, we realized that achieving medical-grade protein purification involves multiple sophisticated steps and careful selection of purification methods. Our next step is to refine our process using her recommendations, particularly focusing on achieving the desired purity levels through optimized chromatography techniques.

5.3 Doctor Feedback on Product

5.3.1 Interview Transcript

Doctor Ding From Benq Hospital Orthopedics Department

5.3.2 Interview Analysis

We recently had the opportunity to meet with Dr. Ding, the orthopedic director at Nanjing BenQ Hospital, to gain insights into the clinical translation of our gradient-controlled release bone repair scaffold, which is designed to gradually release cellular factors to promote bone regeneration. Dr. Ding's expertise in orthopedic surgery, particularly his experience with bone trauma and reconstruction, made him an ideal expert to consult as we continue to refine our product for eventual clinical use.

During the interview, we discussed the main features of our scaffold, including the controlled release of cellular factors such as BMP4 (Bone Morphogenetic Protein 4) and VEGF (Vascular Endothelial Growth Factor), which are designed to enhance osteogenesis and vascularization. We explained how the scaffold would integrate into the body, releasing these factors over time to support the natural bone healing process. Dr. Ding was impressed by the concept but emphasized several critical challenges we would need to address before translating the product from research to clinical application.

One of the first issues Dr. Ding raised was the regulatory pathway for such a product. He explained that medical products involving cellular factors and biomaterials must undergo rigorous pre-clinical testing, including animal studies, to ensure both safety and efficacy. The results from these studies would be crucial in securing approval from regulatory bodies, such as the National Medical Products Administration (NMPA) in China, which governs medical devices and biomaterials. Dr. Ding stressed that regulatory requirements are stringent when it comes to products that release biologically active substances within the body, as there is always the risk of unforeseen side effects, such as excessive inflammation or improper bone formation.

Next, Dr. Ding highlighted the importance of controlled degradation rates in the scaffold. He reiterated that one of the most critical factors for successful bone regeneration is ensuring that the scaffold degrades at the same rate that the new bone tissue regenerates. If the scaffold degrades too quickly, it may compromise the structural integrity needed during the healing process, leading to incomplete bone fusion or instability. Conversely, if it degrades too slowly, it could obstruct the natural healing process by preventing new bone from fully forming in the affected area. Dr. Ding suggested that we conduct long-term in vitro and in vivo studies to fine-tune the degradation rate and ensure optimal performance.

We also discussed the release kinetics of the cellular factors embedded within the scaffold. Dr. Ding noted that while our design aimed to release BMP4 and VEGF gradually, it would be important to verify that the release occurs at a pace that matches the body’s healing needs. He mentioned that a gradual release over several weeks would likely be ideal, as the healing process typically takes time, and overstimulation of bone growth could lead to complications like ectopic bone formation or excessive tissue growth. He suggested that we closely monitor the pharmacokinetics of these factors in future studies.

Dr. Ding was also keen to understand how our scaffold compared to existing bone repair products on the market. He pointed out that most bone graft materials, such as hydroxyapatite-based scaffolds, are relatively passive and rely solely on providing structural support rather than actively promoting regeneration through cellular factors. He expressed optimism that our approach—combining mechanical support with bioactive cellular factor release—had the potential to significantly improve patient outcomes, especially in cases of large or complex bone injuries where natural healing is slower or incomplete.

However, Dr. Ding also emphasized the cost considerations involved in developing and producing a scaffold that incorporates advanced materials and bioactive compounds. He advised that, while the technology is promising, the high cost of manufacturing and purifying cellular factors could be a barrier to widespread clinical adoption. He recommended exploring cost-effective manufacturing processes or partnerships with established pharmaceutical companies that specialize in biomaterials to mitigate production costs.

By the end of the interview, Dr. Ding provided a roadmap for our next steps. He suggested we start by conducting thorough pre-clinical studies, focusing on both safety and efficacy, and work closely with regulatory experts to navigate the approval process. He also recommended beginning small pilot trials in collaboration with hospitals to gather early clinical data and refine the product based on real-world feedback.

Takeaway:

Based on Dr. Ding’s feedback, it is clear that the transition from laboratory research to clinical use will require extensive pre-clinical testing, including animal studies, to ensure safety and efficacy. We must also focus on fine-tuning the degradation rate of the scaffold and the release kinetics of the embedded cellular factors to optimize the bone healing process. Additionally, we need to consider the regulatory and cost challenges associated with developing a clinically viable product. The key takeaway from our interview with Dr. Ding is that while our gradient-controlled release bone repair scaffold holds great potential, significant work remains in addressing the regulatory, technical, and cost-related hurdles. By prioritizing long-term studies on degradation rates, release kinetics, and regulatory compliance, we can better position our product for successful clinical application.

5.4 Patient Acceptance Survey

5.4.1 Interview Transcript

The purpose of our patient survey is to understand patients' awareness and satisfaction with current bone repair materials and treatment methods. We aim to gather their feedback to improve our bone repair product, ensuring it meets the actual needs of patients and enhances treatment outcomes.

Below is the raw data from our survey:

We are committed to ensuring that our patient surveys comply with all relevant ethical guidelines and regulations. The purpose of the survey is to gather insights about patient experiences with bone repair treatments, with the ultimate goal of improving medical products and services. We prioritize patient safety, confidentiality, and informed consent throughout the entire process.

Here are some of the ethical guidelines we strictly adhere to:

Informed Consent

All participants were fully informed about the purpose of the survey, the nature of the questions, and how their data would be used. Participation was entirely voluntary, and patients were free to withdraw from the survey at any time without any consequences.

Confidentiality and Data Protection

Personal data collected from the survey respondents was anonymized to protect their identity. We ensure that all information is stored securely and is only accessible to authorized research team members. No personal identifying information will be shared with third parties.

Non-Coercion

Patients were not coerced or pressured to participate in the survey. Participation was based on their willingness, and no form of financial or other compensation was offered that could influence their decision to take part.

Ethics Approval

Our survey protocol was reviewed and approved by an ethics committee to ensure compliance with medical research standards and guidelines. This approval confirms that our research adheres to the highest standards of ethical conduct in patient surveys.

By adhering to these ethical principles, we ensure that the survey is conducted in a respectful and responsible manner, protecting the rights and well-being of all participants.

5.4.2 Interview Analysis

Based on the results from the patient survey on bone defect treatment methods, we can analyze patient dissatisfaction and identify areas for improvement with regard to bone repair materials. Our goal is to understand the limitations of existing materials and to introduce our advanced bone repair solution to meet patient needs more effectively.

1. Analysis of Survey Results

(1) Understanding of Current Treatments:

A majority of patients are familiar with current treatment options like autografts and allografts, with 60.32% having a good understanding of autografts and 49.21% understanding allografts.

However, the familiarity with artificial bone materials is notably lower, with only 47.62% of respondents having an adequate understanding, and 23.81% indicating only a moderate understanding. This suggests that there is room for education and increased awareness regarding newer synthetic options.

(2) Satisfaction Levels

Satisfaction with autografts is relatively low, with 41.46% of patients expressing dissatisfaction. Although autografts are biocompatible, the limited supply of donor tissue and the potential complications seem to contribute to this dissatisfaction.

For allografts, dissatisfaction remains high, with 44.18% expressing moderate to high dissatisfaction due to issues such as immune rejection and the limited availability of suitable donors.

The most striking dissatisfaction comes with artificial bone materials, where 51.43% of respondents were dissatisfied. This is likely due to concerns about biocompatibility, infection risks, and the lack of biological activity. This highlights an opportunity to improve synthetic options with advanced bioactive properties.

(3) Most Common Concerns

Biocompatibility emerged as the top concern, with 66.67% of respondents worried about poor compatibility between bone repair materials and the human body. This is a critical issue that needs to be addressed with better integration between the repair material and the host tissue.

Other concerns include immune rejection (57.14%), infection risks (45.24%), and the lack of bioactive components in current materials (52.38%). These concerns align with the limitations of current synthetic materials, underscoring the need for a new approach that incorporates both mechanical strength and biological activity to promote healing.

(4) Patient Experience

When asked about the materials they had used, the majority reported using allografts (64.29%) and artificial bone materials (52.38%). However, the fact that over half of the patients were dissatisfied with their experience suggests that these materials are not meeting patient expectations, either in terms of recovery or ease of use.

2. Proposal for Our Bone Repair Material:

Based on these findings, it is clear that current bone repair materials, particularly synthetic ones, are not fulfilling patient needs. The common complaints about biocompatibility, immune rejection, infection, and a lack of biological activity indicate that there is a significant gap in the market for a more advanced solution. Our product, which features gradient-controlled release of cellular factors, directly addresses these issues by integrating:

(1)Enhanced Biocompatibility

Our material is designed to work harmoniously with the body, reducing the risk of immune rejection. This aligns with the top concern of biocompatibility raised by 66.67% of respondents.

(2)Bioactive Components

By embedding cellular factors such as BMP4 and VEGF, our material promotes osteogenesis and vascularization, addressing the lack of biological activity identified by 52.38% of respondents. This offers a significant advantage over existing synthetic materials, which patients find ineffective in promoting true bone healing.

(3)Controlled Release and Degradation

Our product provides a sustained release of cellular factors and degrades in sync with the body’s healing process, ensuring that the material supports the bone until it is no longer needed. This addresses the concerns about premature degradation or lingering material that hinders healing.

Takeaway:

From the survey, it is clear that patients are not satisfied with current bone repair treatments, particularly in terms of biocompatibility, immune response, and effectiveness in promoting bone healing. This dissatisfaction creates a significant opportunity for our gradient-controlled release bone repair material. Our product not only resolves the issues of poor compatibility and lack of bioactivity but also provides a controlled and sustained healing process, ensuring better patient outcomes.

Through this survey, we also have identified key areas where current bone repair materials fail to meet patient needs. Our solution, with its bioactive properties and advanced biocompatibility, addresses these concerns directly. This product has the potential to significantly improve patient satisfaction by offering a more effective, reliable, and safe treatment for bone defects.

5.5 Regulatory and Policy Review

5.5.1 Interview Transcript

Professor Ma, PhD in Pharmacy, Kyoto University

5.5.2 Interview Analysis

After systematically learning professional knowledge such as molecular biology and reading literature, we began detailed procedures of human practice part. We are lucky to invite professor Ma from Kyoto University, who is specialised in drug regulation, biological policy and law. He first explained to us that drug supervision has been taken seriously in the world, that it’s essential to understand the rules and comply them during our project. He walked us through related policy in China, ethical issues and specific procedures to accomplish approvals by departments. He pointed out that we should protect our rights, use patent protection, trademark protection, trade secret protection, copyright protection to ensure the security of research results. He stressed that clinical trials should be conducted in strict accordance with regulations and policies to avoid ethical and biosafety issues.

Takeaway:

With a clearer understanding of relevant laws and regulations, we will carry out relevant steps in detail and use legal tools to protect the rights and interests of the project results to ensure the smooth progress of the project

5.6 Medical Device Application Feasibility

5.6.1 Interview Transcript

Professor Ma, PhD in Pharmacy, Kyoto University

5.6.2 Interview Analysis

After learning about the specific technology and budgetary costs of purifying the protein to pharmaceutical grade, interviewing doctors about their opinions and recommendations for this product, and consulting about the policy and legal environment for this project, we interviewed Mr. Ma, who teaches at Kyoto University, about the feasibility of applying for this project as a medical device. First, Mr. Ma explained the definition of medical devices in China and confirmed that this product meets the Chinese definition of medical devices in terms of treatment and functional improvement. Mr. Ma also introduced us to the specific process of registering a medical device, explaining the materials that need to be submitted as well as the matters that need to be taken care of. Mr. Ma then explained how to ensure the compliance of the product and some of the compliance review steps that we need to go through. Mr. Ma then explained how to carry out risk assessment and management, and cited two cases of successful listing of similar products for our reference. Finally, Mr. Ma gave us five suggestions for our project, which benefited us a lot.

Takeaway:

After an interview with Mr. Ma, we learned about the specific process of medical device registration and what we need to pay attention to, as well as how we should pass the compliance review and conduct risk assessment and management. Next, we will have a more in-depth understanding of medical device registration and other aspects, and we will visit the company offline to investigate the feasibility of landing the protein production of this product.

5.7 Regulatory Oversight and Risk Management

5.7.1 Interview Transcript

Lawyer Nie Xue has thirteen years of experience as a clinical physician, having worked as a physician in the emergency department, internal medicine department, and anesthesiology department. He later passed the national unified postgraduate entrance examination and entered the Peking University Law School to pursue a master's degree in law. He systematically studied legal knowledge and successfully obtained a master's degree. He is currently a partner of Huawei Law Firm.

5.7.2 Interview Analysis

Interviewee

Attorney Nie is a professional with both clinical medical experience and legal practice experience, specializing in medical dispute legal affairs.

Body

1.Project Introduction: Our team is developing a new type of spinal fusion surgery material that can slowly release cytokines such as VEGF and BMP to promote angiogenesis and bone tissue regeneration, addressing the limitations of current technology regarding the use of autologous and allogeneic bones.

2. Medical Regulatory System: Attorney Nie pointed out that during the medical device development phase, laboratory work is autonomous, but the clinical trial phase requires a strict regulatory approval process. This includes ensuring the safety and efficacy of the product, as well as approval from the hospital's ethics committee.

3. Legal Risk Management: Attorney Nie discussed how to ensure the safety and efficacy of medical products through clinical trials and to clearly state risks in product instructions, ensuring full traceability to reduce legal risks.

4. Medical Accident Liability: If losses are caused by improper doctor operation, it is necessary to determine whether there is fault in the diagnostic and treatment behavior and whether there is a causal relationship with the damage consequences. If there is fault, the hospital must bear the corresponding medical damage liability.

5. Medical Ethics and Protection of Minors: Attorney Nie emphasized the importance of adhering to medical ethics in drug development, especially the protection of minors, which requires obtaining the informed consent of guardians as well as the consent of the minors themselves.

6. Drug Development Laws and Regulations: China encourages drug development and has established corresponding laws and regulations to protect the interests of developers and patent holders.

7. Intellectual Property Protection: Attorney Nie discussed the role of patents and trade secrets in intellectual property protection and the legal measures taken in the event of infringement.

8. Compulsory Licensing: During the patent protection period, if the price of the drug is too high and affects the accessibility of the drug, compulsory licensing can be authorized for other companies to produce, thereby improving the accessibility of the drug.

9. Implementation of Laws and Regulations: Attorney Nie believes that the biggest problem at present is not the imperfection of laws and regulations, but how to ensure that they are effectively implemented.

10. Misuse of Medicine Cases: Attorney Nie mentioned that in China, cases of misuse of medicine are relatively rare.

Takeaway:

In the realm of medical device development, such as the creation of new spinal fusion surgery materials, adherence to stringent regulatory systems and ethical requirements is paramount to ensure safety and efficacy. Legal risks are effectively managed by conducting thorough clinical trials and maintaining transparent disclosure practices, which in turn help to mitigate potential legal liabilities that depend on the presence of faults in treatment and their direct causal link to patient damages. Upholding medical ethics is especially critical in pediatric care, where the protection of minors is prioritized.

China's robust regulatory framework not only supports drug development but also ensures the rights and interests of trial subjects are safeguarded. Intellectual property protection is a cornerstone for successful R&D, with mechanisms like compulsory licensing being employed to balance the accessibility of drugs with the respect for patent rights. Ultimately, the diligent implementation and enforcement of these regulations are essential for achieving medical safety and for the protection of patients' rights and interests, underscoring the interconnected nature of these various aspects in the medical and legal spheres.

In China, cases of misuse of medicine are not common, and more attention should be paid to let people to notice and avoid it. For our project cell factors usually have side effects and are not applicable to any symptoms. However, in the current diagnosis and treatment system, the problem of excessive medication is quite common. We should consider the situation of our products being abused and prepare corresponding measures and plans. Please refer to the legislative proposal and draft legislation for details.

5.8 Legislative Proposal

Legislative Proposal: Establishing a Comprehensive Regulatory System to Prevent Drug Misuse

Introduction

With the rapid advancement of medical science, drugs play an indispensable role in treating diseases and safeguarding public health. However, the problem of drug misuse has become increasingly prominent, particularly in primary healthcare settings. Overprescription, irrational drug use, and disregard for safety protocols are common occurrences, posing serious risks to patients and contributing to the waste of medical resources. The misuse of drugs also exacerbates the emergence of antibiotic-resistant bacteria and could lead to drug dependency, threatening long-term public health. This legislative proposal aims to establish a comprehensive regulatory framework to prevent drug misuse, protect patient rights, and promote the sustainable development of the healthcare industry.

I. Problem Statement

Current Situation

There is a significant disparity in drug usage standards between urban hospitals and grassroots medical institutions. While large hospitals tend to follow strict protocols, drug overuse is still prevalent in many rural and community healthcare settings. Common issues include over-prescription, irrational polypharmacy, and excessive dosages, resulting in unnecessary side effects for patients and elevated healthcare costs.

Causes

Drug misuse stems from several factors, including insufficient professional training for healthcare providers, inadequate patient education, and the absence of a robust regulatory mechanism. Some doctors and medical institutions prioritize short-term efficacy and profits, neglecting the long-term risks of inappropriate drug use. Patients, lacking sufficient knowledge, often rely entirely on their doctors’ prescriptions without understanding potential risks. Additionally, regulatory loopholes and delayed enforcement have allowed malpractice to continue unchecked.

Consequences

Drug misuse has both immediate and long-term repercussions. The overuse of antibiotics, for example, accelerates the development of superbugs, which are resistant to current treatments. This complicates future treatments and increases healthcare costs. Meanwhile, drug dependency and addiction are growing problems in society. Furthermore, the wasteful use of medical resources creates a financial burden, stretching an already strained healthcare system.

II. Legislative Principles and Goals

Legislative Principles

Scientific Foundation: Drug use guidelines should be based on comprehensive clinical research and scientific data.

Patient Safety: Ensuring patient safety is the top priority in drug prescription and use.

Economic Feasibility and Fairness: The proposed legislation should balance the cost of healthcare with public health benefits, ensuring that all patients receive fair and equal treatment.

Legislative Goals

Establish a robust regulatory system that oversees drug use in all healthcare settings.

Strengthen the education and training of doctors to improve their professional knowledge and ethical standards.

Enhance public awareness of drug use to empower patients to make informed decisions.

Implement a strict penalty and incentive system to curtail drug misuse and encourage responsible medical practices.

III. Proposed Measures

Develop and Refine Drug Use Guidelines

A comprehensive set of guidelines for drug use should be developed, clearly defining indications, dosages, and contraindications for various drugs. These guidelines will serve as a reference for physicians to ensure safe, effective, and rational drug use. For example, maximum dosage limits should be established to prevent over-prescription.

Strengthen Medical Oversight and Enforcement

A regulatory body should be established to supervise and evaluate drug use practices in hospitals and clinics. Regular inspections and audits should be conducted to ensure compliance with drug use guidelines. Violations should be met with administrative penalties, including fines and license suspensions, and in severe cases, legal action could be pursued under criminal law.

Increase Doctor Training and Education

Regular training programs should be implemented to educate healthcare professionals on rational drug use and emerging medical trends. These programs will not only enhance their expertise but also instill a sense of responsibility toward patients. Doctors should also be encouraged to participate in academic exchanges and research to foster innovation in drug use and patient care.

Raise Public Awareness

Public health campaigns should be launched to educate patients about the importance of responsible drug use. Patients should be informed of the potential risks associated with over-prescription and misuse, empowering them to engage in informed discussions with their doctors. Additionally, a patient feedback mechanism should be established to identify and address any drug misuse promptly.

Incentive and Penalty Mechanism

Incentives: Medical institutions and doctors who demonstrate excellence in rational drug use should be rewarded with financial incentives, public recognition, and policy support to encourage wider adoption of best practices.

Penalties: Medical professionals or institutions that engage in severe drug misuse will face fines, license suspensions, or even criminal charges depending on the severity of the violation. Those found guilty of negligence leading to patient harm will be publicly named and penalized according to the law.

In the end

Drug misuse remains one of the pressing challenges in healthcare, jeopardizing public health and straining medical resources. This legislative proposal outlines a framework that focuses on scientific, safe, and equitable drug use practices. Through a combination of strict regulation, professional training, and public education, we hope to reduce drug misuse and enhance the overall quality of healthcare. We call on legislative bodies to consider these proposals and take swift action to establish a regulatory system that prioritizes patient well-being, professional responsibility, and public safety.

6 Project Publicity and Education

6.1 Community Outreach on Bone Health Education

While a new therapeutic material is being developed, it is appropriate to promote it and introduce the diseases it is used for. Our project is about bone repair. In our country,China, a lot pf people are facing bone health problem, especially teenagers, but while our research is going on, we notice that there is a lack of bone health education whether in society or in school. Therefore, for these reasons, it is important to conduct education and promote knowledge of it.

In August, we give a lecture to teenagers, which is the group most at risk of bone health problems, in Langqin Garden community. This lecture aims to promote knowledge of bone health and teach teenagers to prevent bone health problems.

Many teenagers and some adults came to listen to our lectures. During this lecture, we use physical model to introduced knowledge about human’s bone and bone problems that people(especially young people)are facing, and told teenagers the characteristic of their body and bones, told them how to prevent bone health problems in their daily life.

Also, we prepared some Scoliosis Meters. . In our community activity, on a voluntary basis, We use spinal assessments to measure teenagers' spines, determine if they are at risk of bone health problems, and provide advice.

Our lecture in community was well received and had good effect, the teenagers like it, they smiled and thanked us after the lecture and said that they had gained a lot of knowledge of bone health. The community staff also expressed their recognition of our activity, after the activity they told us that our lecture is “excellent and very meaningful”

6.2 CCIC Bone Health Awareness Lecture

Truly effective education and publicity require thorough consideration. The majority of people facing bone health problems are adolescents, but that doesn't mean we don't have to do our bone health education to adults, adults can also face bone problems, also, Now or in the future many adults or people around them will have children of their own, it is necessary to let them know how to help their children prevent bone health problems. Education in this kind of thing should be for all ages.

Members of our team went to participate in the conference of China iGEMer community(ccic), which is a communication activities between Chinese iGEM teams, during this activity, In addition to communicating with other teams, we held a lecture about bone health to university students in Xi 'an Jiaotong Liverpool University.

In our lecture, we spread bone knowledge and use our physical model to introduce bone health problem and share how to prevent bone health problems, we interact with the audience with an award-winning question to enliven the atmosphere and promote the audience's understanding of bone health and bone knowledge, and in the middle of the lecture, we prepared two Scoliosis Meters and test the spine of the audience to let they if they are at risk of facing bone health problem(on a voluntary basis).

At last, we gave souvenirs to audience and call on everyone to pay attention to their own bone health and The bone health of the people around them, to work for a healthier society.

This lecture let students gain knowledge about bones and preventing bone health problems, and got a good response. University students show their interest in our activities when participating, and act positively. Our lecture went well, we have successfully promote knowledge of bone health.

6.3 CCIC Project Exhibition & Poster Presentation

Introduction

In July, our team attended the 11th CCIC (Conference of China IGEMer Community Synbio Nexus). As part of the event, each team was given the opportunity to present their project through a poster display. Our art team designed a poster that effectively showcased our work. Throughout the conference, our poster attracted interest from fellow IGEMers and judges, who stopped by to learn more about our project.

Discussions with Other Teams

Many teams and guests were enthusiastic about the potential of our project, but they also raised important questions. One of the guest attendees, JiangShan, a former IGEMer turned entrepreneur, visited our stand and provided valuable feedback. While he found the technical aspects of our project solid, he suggested that we delve deeper into the political and legislative implications, particularly concerning safety and regulatory approval. This advice encouraged us to consider these critical aspects more thoroughly. In addition to JiangShan's insights, we engaged in discussions with other student teams who had similar ideas but took different directions with their projects. Other teams also raised technical questions, such as how we plan to implement the material into the human body, leading to insightful exchanges of ideas.

Takeaways

The conference provided us with not only technical feedback but also broader perspectives on our project. We gained awareness of the importance of considering political and legislative factors, which are essential for the successful adoption of our product. Moreover, the discussions highlighted concerns about patient acceptance, especially regarding invasive procedures, even when they are proven safe. These insights will be invaluable as we refine our project and address both technical and non-technical challenges.