Immunomodulatory and Pro-Angiogenic Porous Scaffold for Large Diameter Wounds

Biomaterials; Molecular, Cellular, and Tissue Engineering

The focus of this project is to interrogate the mechanism and impact of our existing material treatment in large wounds (~100x volume of small animal study) in a clinic relevant large animal model.

Research Interests
  • Diabetic complications
  • wound healing
  • Angiogenesis
  • immunomodulation

Diabetic wounds, including diabetic foot ulcers (DFU), are notoriously difficult to manage, due primarily to being highly inflammatory and exhibiting poor tissue reformation. DFUs exhibit 60% re-ulceration rates after 3 years, leading to an estimated 20% of DFU patients later undergoing lower limb amputation. Application of biomaterial scaffolds to non-diabetic wounds support faster wound closure, however diabetic wounds present unique challenges that make biomaterial use difficult, particularly in treatment of large diameter wounds in large animal or humans. We have developed an inexpensive and synthetic biomaterial for diabetic wound treatment based on our Microporous Annealed Particle (MAP) gel platform technology that uses microporosity and microheterogeneity to modulate host immune response and form spontaneous chemotactic gradients, respectively. MAP has had notable success in small animal models of full-thickness skin wound healing (non-diabetic and diabetic). The focus of this project is to interrogate the impact of our existing material treatment in large wounds (~100x volume of small animal study) in a clinically relevant large animal model of healthy skin wound healing as a pilot study to justify further funding for large animal diabetic wound studies. Further, we will incorporate the spatio-temporal chemokine data generated from this animal model into a computational molecular transport model to better understand and improve our material approach.

Desired outcomes

While expected results are that the current biomaterial device will enhance skin wound healing in a large animal model relative to current standards of care, our desired outcome of the experimental arm of this project is the generation of molecular data showing the spatial and temporal distribution of important chemokines within the skin wound. This data and molecular affinity data determined in vitro will then be incorporated into a molecular transport model to help in the identification of important material variables for harnessing the endogenous healing capacity of wounds.