Multifunctional Cell Instructive Silk-Bioactive Glass Composite Reinforced Scaffolds Toward Osteoinductive, Proangiogenic, and Resorbable Bone Grafts

Abstract

The successful regeneration of large volume bone defects necessitates the use of proangiogenic and resorbable scaffolding matrix. Impaired and slow ingrowth of host vasculature within implanted grafts greatly compromises its effective osseointegration. By addressing this, it is demonstrated that the use of copper doped bioactive glass functionalizes silk microfiber reinforcements to improve the physicochemical and osteoinductive properties of two silk scaffolding matrices (mulberry Bombyx mori and non-mulberry Antheraea assama) employed in the study. The reinforced composite matrices increase the surface area and present an open porous biomimetic micromillieu favoring stem cell and endothelial cell migration within the matrix. Biochemical results indicate the stabilization of hypoxia-inducible factor-1α and expression of C-X-C chemokine receptor type-4 in adipose derived human mesenchymal stem cells, which regulate the downstream proangiogenic signaling and endothelial cell homing, respectively. Osteoinduction, matrix turnover, and resorption effectiveness are favored better in the non-mulberry silk matrices. The composite matrices significantly promote neo-osseous tissue formation in volumetric femur defect in rabbits with periosteal restoration seen in the non-mulberry silk composite matrices. Evidences of total resorption, enhanced vascular-fibrous tissue ingrowth within the scaffold, vouch for the potential clinical translation of these developed composite silk matrices.

Silk fibroin (mulberry and endemic Indian non-mulberry silk), a widely renowned biopolymer herein is used to derive cell instructive bone scaffolding platforms. These bioactive glass functionalized silk microfibers reinforce composite matrices dictated stem cell differentiation, matrix maturation, endothelial cell migration, homing and network formation in vitro and consequently help in complete restoration of volumetric bone defects in rabbit femurs.

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