Toward the development of a novel mineralized collagen scaffold for bone repair and regeneration

Abstract

Due to an increasing demand for more functional bone-repair materials, implants composed of mineralized collagen have garnered interest. The process as to how collagen fibrils become mineralized both in situ and in vitro is not yet well understood. Additionally, preparing scaffolds possessing similar mechanical and structural features as those found within bone remains a difficult process. The benefit of preparing an implant composed of mineralized collagen that can be mechanically tailored and holds a chemical and structural profile similar to bone is widely recognized. The studies contained herein describe a novel process for preparing an acellular, naturally crosslinked mineralized collagen scaffold based on a tailorable alternate soaking mineralization procedure. The developed mineralization procedure led to a close integration between bone-like mineral and aligned collagen fibrils in produced scaffolds. Through adjustments in the manufacturing procedure, the mechanics of both individual fibrils and whole sheets were able to be controlled, as determined through nanoindentation and flexural testing. It was found through in vitro investigations that mineralized scaffolds preferentially promoted the differentiation of pre-osteoblast cells, measured by ALP activity and OCN content. Traditional methods of preparing mineralized collagen scaffolds often use reconstituted, randomly oriented collagen fibrils, mineralized in such a way that often ignores the specific mineral-collagen association found in nature. The motivation behind this work was to develop a mineralized collagen scaffold that paid particular attention to fibril alignment as well as mineral integration and subsequent material mechanics. The work described herein presents, for the first time, the ability to easily control the mechanics of mineralized collagen fibrils and aligned sheets in a predictable way through simple modifications in their mineralization procedure. Additionally, insights gained from detailed structural and chemical analyses allow for a wider understanding of the effects various chemical additives have on prepared mineral crystals; widening our understanding on biomineralization.