The extracellular matrix (ECM) is a 3-dimensional structure and an essential component in all human tissues. It's an extensive network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body. Currently, tissue engineering has employed new ways to create bio-inspired scaffolds able to mimic native ECM in scale by combining growth factors with biopolymers. These advanced extracellular matrix products are thought to encourage ECM deposition, cellular ingrowth, and neotissue formation, all of which are crucial for wound healing.

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Extracellular Matrix and Wound Healing

Wound healing is a complex and coordinated series of events that help maintain homeostasis and protect the whole organism. Damage to the ECM through injury leads to a series of healing events, often known as the "wound healing cascade." 

The first event is homeostasis (clotting and coagulation), followed by inflammation, proliferation, and remodeling. These stages are not mutually exclusive, overlap in the organism, and typically occur quickly, with the remodeling phase taking longer than the rest.

The extracellular matrix is primarily constituted of water, proteins, and polysaccharides. The two major proteins found in the native ECM are collagen, which gives structural and tissue integrity, and elastin which allows for tissue elasticity. Studies have endorsed using ECM to modulate wound healing by regulating cell behavior, including proliferation, adhesion, migration, and survival.

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Benefits Of Advanced Extracellular Matrix (ECM) Products in Wound Healing

Many advanced ECM products for wound healing in the market are created to mimic ECM by increasing the rate of wound healing in secondary intention wounds. Among these, decellularized ECM tissues are a worthy alternative to native ECM for reconstructing cutaneous lesions since they maintain the complex protein structure and provide functional domains for cell differentiation. Some examples are Acell wound powder, Alloderm, Permacol, GraftJacket, and PalinGen membrane

In every phase of the wound healing process, the whole ECM plays several influential roles. These include:

Delivery Of Growth Factors and Cytokines

ECM proteins like fibronectin, proteoglycans, collagen, and heparin bind many growth factors such as fibroblast growth factor, bone morphogenic proteins, and epidermal growth factor. ECM proteins degradation by proteolytic enzymes in response to wounds can induce the local release of the growth factors, thereby modulating the process of wound healing. 

Recent studies show that ECM products may be critical in shaping the stem cell niche to maintain stem cell homeostasis.

Clotting and Coagulation

Wound healing begins immediately after an insult to the tissue, and this is when ECM initiates clotting and coagulation. Nanofiber ECM products have a morphological resemblance to the native ECM of the skin, which allows them to mimic the structure and function of ECM. 

Nanofiber products can protect the wound from protein and fluid loss and aid in the removal of exudates from the wound site hence improving homeostasis.

Tissue Repair

Regenerating a fully functional tissue requires that both the complex function and fibrous form of the native ECM be mimicked by the wound healing matrices or skin substitutes. Elastin, a protein mainly associated with collagen in the ECM of connective tissues, helps tissues to return to their original shape after a temporary deformation. ECM products comprising mainly elastin are vital for tissues that experience repetitive rebound stretches during wound healing.

Remodeling

Remodeling is the final phase in wound healing. Here, loose and highly hydrated ECM is gradually replaced by denser ECM composed mainly of collagen, promoting the restoration of tissue architecture. 

Collagen-rich ECM products are usually used in this phase to speed up wound resolution, which begins as the number of extracellular collagen increases and fibroblasts decrease their collagen production. This allows the scar to gradually strengthen even though the scar tissue will not be as strong as normal uninjured skin since healed wounds never regain their full tensile strength.

Chronic Wound Healing

Achieving the healing of chronic diabetic ulcers, large traumatic wounds, or burns is a major clinical challenge. Chronic wounds develop when normal wound healing is delayed or disrupted by continuous inflammation, angiogenic response, persistent infection, and necrosis. The longer a wound takes to heal, the higher the chances of foreign bodies entering the body and causing infections. 

Advanced ECM products – especially decellularized ones – can be used to avoid immune reactions and inflammation responses that cells could induce, which otherwise may cause implant rejection. This is beneficial for chronic wounds as it provides the optimal environment for the wound healing process.

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Bottom Line

There is a rise of new therapeutic strategies – such as advanced ECM products – that have similar structural, functional, and chemical properties that mimic the native ECM. These products provide a suitable environment for regulating cells' differentiation, growth, and migration. Advanced ECM products are extremely beneficial as they protect wounds, provide a scaffold for cell proliferation, and accelerate wound healing for a desirable therapeutic outcome.

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