Protease Resistant Growth Factor Nanoparticles for Chronic Wound Healing

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PROJECT SUMMARY Older adults are extremely susceptible to chronic wounds such as venous leg ulcers (VLUs), diabetic foot ulcers (DFUs) and pressure ulcers (PUs). These wounds are difficult to treat and often drastic operative interventions such as amputations or free flaps with a clear loss of function are necessary. An increasingly popular approach for the treatment of chronic wounds is the use of recombinant biologics such as growth factors (GF). Elegant work by researchers over the years has shown successful healing induced by numerous GFs in various preclinical wound models developed in animals. Despite these promising results, successful translation of GFs to human patients remains limited. We have identified that this can be attributed to the presence of high levels of proteases present in human chronic wounds that result in rapid degradation of the GF rendering the therapy ineffective. Most animals models of wound healing do not exhibit high protease levels and thus therapies that tend to look promising in animals fail to translate to humans. We have developed innovative nanoparticles (NP) that not only deliver the GF at the wound site but also protect it from protease mediated degradation. Our work has shown that these NPs improve the half-life of the growth factor in human chronic wound fluid and wound healing in young diabetic mice in the presence of proteases. In this proposal, we intend to translate these promisinig NPs towards the healing of chronic wounds in the elderly. However, there are significant differences in the wound healing of aged and young animals. Therefore, in the R21 phase we propose to test the NPs in aged wounds and in the R33 stage we will focus on the preclinical development of the NPs. We will use this data to prepare an FDA application for first in human studies focused on efficacy of NPs on the healing of chronic wounds. This project will enable us to bring this promising technology closer to the bench side. As a new therapy for the treatment of difficult to heal chronic wounds, it will significantly reduce the cost and burden of chronic wounds in the health care system while improving patient outcomes and quality of life.