Project
Human Practices
Dry Lab
Wet Lab
Inclusivity
Measurement
Plant
Sustainable
During life, people may suffer in a way or another. Unbearably, suffering physically, mentally, and socially, burn patients undergo mysterious awkward moments for days, months, and even years. Noticeably, psychiatric stigma was common among all burn victims due to the disfigurement of their skin which in return made them feel depressed, anxious, introverted. Unfortunately, the burn cicatrix can even restrict daily activities such as eating and drinking due to perioral facial burn. Their journey is quite hard! Rehabilitation takes a lot of time and requires a lot of endurance to deal with scar restraints. Burn scar is a real issue which requires an intervention!
Plastic surgery doctors were our guide toward the whole healing process. Passing by the emergency management reaching topical treatment, grafts, and advanced dressing ending by managing disfiguring scars which really stole our minds to the possibility of “scarless wound healing”!
Severe burns influence various aspects of a person's life, including their education, social life, and psychological well-being. These lead them to suffer from physical limitations, fear of judgment, and social isolation. These lead survivors to significantly drop their work productivity. Additionally, financial burdens on individuals, families, and government due to extensive treatment, including surgeries, rehabilitation, and long-term care. These costs strain the healthcare systems and affect national economies.
In Egypt most burns were of domestic type, especially while cooking due to fire use. Moreover, unemployed patients were the majority of victims, about 67.2% . Of those, 31% were below school age and 25% were students, 41% were housewives and 3.2% were retired. The students face educational hardships because of their psychological state which in return affects their concentration, memory, and cognitive function. Similarly, among the unemployed victims, especially the housewives whose injury might be related to the unsafe cooking stoves and to the open fire cooking. Surely, burn took away these females’ beauty and stripped their self-confidence.
The majority of the previously mentioned burn consequences are attributed to scar formation! If joints are affected, patients struggle with normal everyday activity because of contractures or heterotopic ossifications. Additionally, psychological complications appear such as depression, post-traumatic stress disorder, anxiety, and sleep disturbance which finally leads to a stigmatized person with social engagement barriers.
It is tissue damage due to exposure to heat, cold, friction, chemicals, electricity, radiation or the sun causing both local and systemic effects.
Burn lBurn leads to denaturation of cellular proteins which exceeds the capacity of cellular repair. The cellular destruction leads to inflammatory mediators release such as VEGF, TNF-α, G-CSF, IL-8, and IL-10. Even more, the cellular degradation leads to a hypermetabolic state in which the release of reactive oxygen species from dead tissues, with the inflammatory mediators, causes endothelial cell dysfunction and high vascular permeability (tissue swelling). Finally, a microvascular thrombosis is formed due to clotting factors release, resulting in impairment of tissue healing and greater destruction.
This degree of burns is limited to the outer layer of the skin (epidermis). The burnt area is red, painful, dry and blister-free with a mild change in the skin color.
This degree of burns often involves the epidermis and a part of the deeper layer of the skin (dermis). The burn area appears red, blistered, painful, and may be swollen.
This burn degree destroys the epidermis, dermis and may reach the innermost layer of the skin (subcutaneous tissue). The burn area may look white or blackened and charred.
These burns destroy all layers of the skin and underlying tissue as well as deeper tissue, sometimes reaching muscles and bones. The nerve endings are also destroyed which causes absence of sensation in the burn area.
In the pursuit of addressing scarless wound healing, prior research has explored innovative methodologies. One approach, called TecTissue, combines a multi-glycopeptide scaffold with the recombinant growth factor Leptin B to stimulate fibroblast proliferation—a key step in wound healing. Nanoencapsulation techniques were used to ensure precise delivery of these therapeutic agents. In a simulated setting, TecTissue demonstrated potential in enhancing tissue regeneration while reducing infection risks.
They aim to develop multifunctional wound dressing utilizing synthetic yeasts, with a primary focus on addressing the care of bedsores. The innovative bio-tech bandages are crafted using synthetic yeasts S.cerevisiae, designed to provide three essential core functions. Firstly, the bandages monitor wound healing by tracking changes in oxygen concentration levels. This is crucial as the oxygen concentration in a wound fluctuates based on its healing state, with increased oxygen consumption in the wound area indicating a normal oxygen state in a healed wound and a hypoxic state in a non-healed wound. Secondly, the bandages work to prevent bacterial infections by secreting antimicrobial peptides such as Defensins. This proactive approach helps reduce the risk of infections that can impede the healing process. Lastly, the bandages are equipped to detect bacterial infections by monitoring intercellular communication signals, allowing for early intervention and targeted treatment. By offering these three key functions, YEAST-AID aims to empower non-professionals to effectively and easily facilitate the healing of pressure ulcers, ultimately improving patient outcomes and quality of care.
Another new approach addresses a solution for wound healing by bio- synthesizing spider silk from spidroins, spider silk proteins, using modified Escherichia coli. After purifying the protein, it will be spun into a thread, bundled into an amorphous tissue of spider silk, and bound with a layer of collagen. The modified spider silk promotes wound healing and is applied directly to the affected area after cleansing and disinfecting. The patch improves wound healing by sustaining a moist wound environment, decreasing the inflammation, granulation, and increasing the rate of regenerative phases.
An approach, called a core-shell structured microneedles (PF-MNs) , introduces a core-shell structured microneedle array patch designed to dynamically modulate the wound immune microenvironment for effective scarless wound healing. The patch is composed of a ROS-degradable shell which is loaded with verteporfin and heparin. Thus, it can effectively combat bacterial biofilm, neutralize inflammatory factors, and promote the transition from inflammation to proliferation. By targeting these key factors, PF-MNs demonstrated significant efficacy in promoting scarless wound repair in both acute and chronic wound models.
Tissue therapy approaches, based on biological sources, have emerged as promising strategies for scarless wound healing. Skin transplantation, encompassing auto-, allo-, and xeno-transplantation, have been widely explored. While autotransplantation offers the advantage of immune compatibility, its feasibility is limited.
A promising alternatives have emerged like Fish-derived acellular matrices, such as tilapia acellular dermal matrix (TADM), which provide a scaffold for wound repair while minimizing immune rejection. These matrices possess structural similarities to human skin, including porous structures and good biocompatibility. Transplantation of TADM has been shown to promote cell infiltration, angiogenesis, and cytokine regulation, ultimately leading to reduced inflammation and improved wound healing outcomes.
Additionally, human amniotic membrane, known for its anti-inflammatory and anti-fibrotic properties, holds potential as an alternative therapeutic option.
SONG-His a Stem Cell-based Occlusive Nutritive Gel of Healing which aims to promote current wound healing treatment especially targeting the scar formation process. Burn was a great application of scarless wound healing for its characteristic scars and contractures. Generally, unlike regeneration, scars are formed due to insufficient viable tissue in the damaged area, allowing scar formation (tissue repair).
| Comparison | Wound Regeneration | Wound Repair |
|---|---|---|
| Description | Cells and tissues are grown to replace lost structures with restoration of normal architecture. (Restore Both function and appearance) | Patching rather than restoring, replacing the damaged tissue with fibrous connective tissue. (Less functional and less aesthetic) |
| Time | At the onset of the damage. | The onset of the damage lasts up to 4 weeks. |
| Cells | MSCs (cell-based therapy) which differentiate into specific cells needed to rebuild the damaged tissue. | Fibroblast and inflammatory cells like MQ and neutrophils. |
| Outcome | Complete tissue replacement | Scar formation (Keloid, Hypertrophic scar) |
| Done By | SONG-H | Normal physiological response |
Therefore, we leverage the regenerative potential of mesenchymal stem cells (MSCs), utilizing a topical hydrogel scaffold to ensure their effective delivery. By introducing MSCs into the wound site via the scaffold, the natural healing cascade will be accelerated, fostering a seamless and scarless restoration of damaged tissue. Indeed, exploiting the unique properties of MSCs, we engineered them to conditionally induce a regenerative protein called yes associated protein (YAP-1), a transcriptional regulator protein involved in cell proliferation and differentiation and regulated by hippocampal pathway. Putting in consideration uncontrolled cell proliferation incidence, YAP-1 control was mandatory! We have implemented a dcas-9 system to induce YAP-1 expression based on the activation of a synthetic receptor called dcas9-synRTK receptor. This receptor is activated in presence of a tissue injury biomarker called vascular endothelial growth factor (VEGF).
YAP-1 will not merely be induced through the hydrogel scaffold MSCs but also through the surrounding viable cells. MSCs communicate with other cells through exosomes, which, in our case, carries YAP-1 mRNA that is regulated by protein specific mRNA switch. Matrix metalloproteinase- 9 (an intracellular tissue injury biomarker) is the key activator of this switch.
By analyzing the market stakeholders, deep-burned patients settled to be the top target. SONG-H aims to fill the gap of the unmet needs of other burn products in the market. It assists in the healing process and decreases the contractures, muscle wasting, and resulting inabilities.
We aimed to study market competitors, customers’ needs, and environmental factors and gather the best plan for market penetration. Furthermore, we prepared a full entrepreneurship model that helped us study our product and know our position among the competitors.
In our long-term plans, SONG-H will be designed to approach all body cells, specifically ones that aren’t capable of dividing as those of heart, neurons, and joints.
SONG-H is a therapeutic platform which integrates synthetic biology and regenerative medicine concepts. While taking into account safety regulations, it simply uses the innate function of MSCs meanwhile delivering a regenerative protein called YAP-1. SONG-H is introduced in the form of a hydrogel topical scaffold which mainly purpose scars either disfiguring or mobility limiting.
We were inspired by the gap in managing scars and noticed the aim of current treatment which focuses on treating burn not its consequences. Reflectively, this led us to direct our efforts towards second and third degree burns, causing massive scar behind.
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