A Tissue Engineered Treatment for Chronic Diabetic Skin Wounds: An Advanced Collagen Wound Matrix Combined with Adipose Derived Stem Cells
Chronic, non-healing skin wounds are a significant clinical challenge in diabetic patients, and few effective treatments are currently available. Often, after many failed treatments, physicians are forced to resort to amputation of the affected extremity due to the high risk of infection and eventual sepsis. An effective treatment to heal chronic diabetic skin wounds is urgently needed to reduce the risk of infection, eliminate the need for limb amputation, and improve the quality of life of people with diabetes. To address this need, we have developed a tissue-engineered treatment that combines a novel electrochemically deposited type I collagen scaffold, termed the advanced collagen wound matrix (CWM), and human adipose derived stem cells. The CWM is fabricated by an electrochemical deposition method, as opposed to a traditional collagen gelation method, which creates a densely packed, robust collagen matrix that possesses excellent material properties for skin tissue engineering. The CWM possesses high porosity, an appropriate degradation profile, and significantly higher tensile strength than a standard gelated collagen scaffold. The CWM is highly biocompatible and supports cellular growth and proliferation well. To increase the wound healing capabilities of this treatment, the CWM is seeded with human adipose derived stem cells. Adipose derived stem cells (ADSCs) are abundant, easily harvested, and well suited for tissue culture. They also possess inherent wound healing properties, making them ideal for treatment of chronic diabetic skin wounds. To fully investigate this treatment, the CWM with and without the addition of ADSCs is used to treat full thickness excisional skin wounds in a murine model of type 2 diabetes and wound healing is monitored to 21 days. In this model, untreated diabetic skin wounds regenerated low volumes of granulation tissue during the first 7 days of healing, then had no increase in granulation tissue formation past the initial 7 days, highlighting the impaired wound healing capabilities associated with diabetes. Treatment with the CWM alone and the CWM combined with ADSCs, however, consistently stimulated significantly increased volumes of regenerated granulation tissue and formed higher quality tissue than the untreated wounds. We prove that the CWM stimulates healthy tissue regeneration in diabetic skin wounds when used both alone and in combination with adipose derived stem cells. We have developed an excellent treatment option for patients with chronic, non-healing diabetic wounds who may otherwise be forced to consider limb amputation.