Multi-material delivery strategies to create deferoxamine-functionalized collagen scaffolds for craniofacial bone repair

Abstract

Craniomaxillofacial (CMF) bone injuries are common and can occur secondary to trauma, bone resection, and congenital abnormalities. While the current standard of care remains allograft or autograft, tissue engineering approaches offer the opportunity for alternative regenerative solutions. Biomaterial design has been central in this effort, with a primary consideration being the incorporation of motifs into biomaterials that accelerate osteogenic differentiation of progenitor cells and subsequent mineral synthesis. However, angiogenic potency, and subsequent angiogenic-osteogenic coupling, represent a critical challenge, as poor angiogenic activity can impair regenerative healing. Deferoxamine (DFO) can mimic cellular hypoxia via iron chelation and has been used as an angiogenic factor. However, its size (<1 kDa) severely limits its retention in the wound area. Here, we report a multi-material approach to improve angiogenic coupling in an osteogenic biomaterial. We report methods to retain DFO in mineralized collagen scaffold via its binding to a second polymer, gelatin, that can be incorporated into the scaffold to boost angiogenic potency while maintaining its osteo-regenerative properties. We employed carbodiimide chemistry to attach DFO to a gelatin backbone and retained 79.6% of the drug over a 7-day culture. Using a composite drug-delivery approach that combines freely soluble DFO with gelatin-bound DFO into the mineralized collagen scaffold, drove increased mesenchymal stem cell metabolic activity and enhanced expression of angiogenic genes in culture over 14 days. This work provides a novel approach to advance acellular regenerative biomaterials for osteogenic-angiogenic coupling processes.