The extracellular matrix (ECM) is a 3-dimensional structure and an essential component in all human tissues. It is comprised of varying proteins, including collagens, elastin, and smaller quantities of structural proteins. Studies have demonstrated the ECM aids in cellular adherence, tissue anchoring, cellular signaling, and recruitment of cells. During times of integumentary injury or damage, either acute or chronic, the ECM is damaged. Through a series of overlapping events called the wound healing phases—hemostasis, inflammation, proliferation, and remodeling—the ECM is synthesized and ideally returned to its native state. This article synthesizes current and historical literature to demonstrate the involvement of the ECM in the varying phases of the wound healing cascade.
Due to its adjustable properties, PAAM-Alg can be modified to mimic various thrombi classifications. Future studies will include obtaining and quantitatively classifying patient thrombectomy samples and altering the PAAM-Alg to mimic the results for use with in vitro thrombectomy studies.
Chronic wounds in patients suffering from type II diabetes mellitus (DMII) where wounds remain open with a complicated pathophysiology, healing, and recovery process is a public health concern. Normal wound healing plays a critical role in wound closure, restoration of mechanical properties, and the biochemical characteristics of the remodeled tissue. Biological scaffolds provide a tissue substitute to help facilitate wound healing by mimicking the extracellular matrix (ECM) of the dermis. In the current study an electrospun biomimetic scaffold, wound healing device (WHD), containing tropoelastin (TE) and collagen was synthesized to mimic the biochemical and mechanical characteristics of healthy human skin. The WHD was compared to a commercially available porcine small intestinal submucosa (SIS) matrix that has been used in both partial and full-thickness wounds, Oasis
®
Wound Matrix. Using a diabetic murine model C57BKS.Cg-m+/+Leprdb/J mice (db/db) wound closure rates, histochemistry (CD31 and CD163), qPCR (GAPDH, TNF-α, NOS2, ARG1 and IL10), and mechanical testing of treated wound sites were evaluated. The WHD in a splinted, full thickness, diabetic murine wound healing model
demonstrated skin organ regeneration, an enhanced rate of wound closure, decreased tissue inflammation, and a stronger and more durable remodeled tissue
that more closely mimics native unwounded skin compared to the control device.
Background
Chronic wounds affect an estimated 8 million people worldwide and are often a result of underlying health conditions, such as obesity, diabetes, malnutrition, etc. The related morbidity and mortality places an increased burden on the healthcare system. Regenerative approaches, which engages and stimulates the body’s innate healing capabilities is addressing the limited successes in current standard of care treatments. Axolotl Biologix is a regenerative medicine company that produces allograft products from the human amnion. Axolotl Ambient™ and Shot™, conditioned media rich in cytokines and growth factors, are derived from human amniotic mesenchymal stromal cells. Axolotl DualGraft™ is a dehydrated, acellular, double layer, human amniotic membrane that encourages soft tissue repair by serving as a barrier, extracellular matrix scaffold, and provides a source of matrix‐bound growth factors.
Methods
Both allografts were used to facilitate repair and regeneration in a patient with difficult to close or intractable full‐thickness wounds. Axolotl Ambient™ was injected into the wound margin and Axolotl DualGraft™ was placed within the exposed wound bed. Wounds were bandaged per standard of care and imaged regularly to monitor wound healing progression. A range of bioassays were performed to ascertain the biological activity of the allografts.
Results
Multiple applications and injections of Ambient and DualGraft resulted in the formation of granulation tissue, restoration of blood flow, pain sensation, epithelialization, and wound closure. Bioassays confirmed the allografts contain measurable amounts of growth factors that promote angiogenesis, proliferation, tissue remodeling and reduction in inflammation.
Conclusions
Clinical application of the allografts in intractable wounds yielded dramatic improvement in wound repair by stimulating the normal physiological wound healing processes by the addition of exogenous growth factors, providing a scaffold in the wound bed, promoting normal blood flow, re‐epithelialization, and tissue remodeling. Longitudinal case studies are ongoing, concurrent with benchtop research to further elucidate the mechanisms of action responsible for reported clinical benefits in difficult to heal wounds.
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