Īngiogenesis is regulated by signaling cascades activated by multiple cytokines released following local injury. The endothelial and other cells within a newly formed vessel not only support improved perfusion, but also release paracrine functions that lead to cellular stimulation surrounding blood vessels within the wound bed. Extracellular matrix (ECM) proteins, comprising several different matrices, also are intrinsic and extrinsic to the structure of blood vessels. Microvascular tissue is generated by the process of angiogenesis, which results in the development of new blood vessels containing vascular endothelial cells, pericytes, smooth muscle cells, fibroblasts and progenitor cells. Insufficient vascularity and a resulting senescent microenvironment are two important common denominators in failed healing. However, there are still many complex chronic wounds that do not heal despite conventional and current advanced treatments, leading to eventual amputation. In addition, recent clinical studies with amniotic membranes, human amnion allografts or processed amnion products such as Epifix ® (MiMedx, GA, USA) have demonstrated efficacy for treating diabetic foot ulcers and other healing problems. A topical recombinant growth factor, becaplermin (Regranex ®, Ortho-McNeil, NJ, USA) stimulates wound healing by promoting angiogenesis, stem cell recruitment and epithelialization. Conditioned media containing expressed factors but no viable cells obtained from adipose tissue may induce angiogenesis and cell proliferation. Skin TE ® (Polarity TE, UT, USA) is derived from a patient’s own skin tissue. Īllogeneic skin graft substitutes containing viable cells such as Apligraf ® and Dermagraft ® (Organogenesis, MA, USA) have been used in wound healing for decades. Other cellular interventions have been studied, including autologous bone marrow-derived stem cells, stromal vascular fraction (SVF) from adipose tissue and other cellular sources, for treating nonhealing wounds in the setting of chronic radiation injury, severe arterial–venous leg ulceration, and with other complex co-morbidities including wounds at amputation stumps. While clinical benefits have been observed, and platelet-rich plasma is widely used, a meta-analysis concluded that the effect on wound healing is relatively small. The earliest of these was autologous platelet-rich plasma, where patients’ blood is drawn and their platelets isolated, concentrated and administered to the wound bed. Effective therapy for patient with severe illnesses, such as advanced diabetes, critical limb ischemia, morbid obesity or cancer, who have chronic wounds can be challenging, due to underlying systemic disease and compromised tissue surrounding the wound.Ī growing number of advanced treatments for wound care involve biological modalities that act on the cellular level. When these measures have failed, additional therapies such as negative pressure wound therapy or hyperbaric oxygen chambers have been utilized. Conventional clinical treatment for chronic wounds include sharp debridement, offloading of the wound to relieve pressure, treatment of infection and surgical revascularization or angioplasty. Such problematic wounds can develop for an array of reasons, such as venous stasis, ischemia, unrelieved pressure, chemotherapy and radiation treatment. In chronic or delayed-healing wounds, however, this process can be severely compromised. During normal healing, angiogenesis leads to revascularization of tissue and the establishment of a functioning microcirculation to deliver oxygen, nutrients and paracrine factors required for proper tissue repair. Nonhealing wounds affect up to 6 million people in the USA, resulting in healthcare expenditures exceeding US$3 billion per year.
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