Osteoinductive Nanosilicate-Based Biomaterials for In Situ Craniomaxillofacial Bone Regeneration

PROJECT SUMMARY A range of synthetic bone graft substitutes loaded with therapeutic growth factors, such as recombinant human bone morphogenetic protein 2 (rhBMP2), are used for reconstructing craniofacial bone defects in patients suffering from trauma, infection, congenital anomalies, and oncologic resection. However, these strategies often involve the administration of supraphysiological doses of growth factors, which have been reported to lead to serious off-target tissue responses, including heterotopic ossification (bone formation at undesirable places), osteolysis, and swelling. The objective of this proposal is to design osteoinductive biomaterials to induce in situ bone regeneration in the absence of exogenous growth factors. This project builds upon the PI’s extensive published and preliminary data on a new class of two-dimensional (2D) mineral-based nanoparticles, known as nanosilicates, to induce osteogenic differentiation of human mesenchymal stem cells in the absence of growth factors. Also, nanosilicate-based shear-thinning biomaterials can be used for minimally invasive cell therapy. The central hypothesis is that nanosilicate-based biomaterials will activate endogenous cells to promote bone formation in the absence of exogenous growth factors. To test this hypothesis three independent specific aims are proposed: (1) Elucidate the molecular mechanism of nanosilicate-induced osteoinductivity; (2) Design 3D printed nanosilicates-loaded microporous scaffolds for rapid cellular invasion and angiogenesis; and (3) Demonstrate in situ bone regeneration using 3D printed nanosilicates-loaded microporous scaffolds. It is expected that the ability of nanosilicate-based biomaterials to induce in situ bone regeneration by stimulating endogenous cells will circumvent the current clinical limitations associated with the use of supraphysiological doses of growth factors. The proposed research is significant because it will advance and expand the understanding of how this new class of 2D nanomaterials can be used in bone tissue engineering. The completion of the proposed work will provide a new class of osteoinductive biomaterials for future studies in larger animal models and eventually advance bone regeneration approaches for humans.