Biomaterial design strategies to address obstacles in craniomaxillofacial bone repair

Abstract

Biomaterial design to repair craniomaxillofacial defects has largely focused on promoting bone regeneration, while there are many additional factors that influence this process. The bone microenvironment is complex, with various mechanical property differences between cortical and cancellous bone, a unique porous architecture, and multiple cell types that must maintain homeostasis. This complex environment includes a vascular architecture to deliver cells and nutrients, osteoblasts which form new bone, osteoclasts which resorb excess bone, and upon injury, inflammatory cells and bacteria which can lead to failure to repair. To create biomaterials able to regenerate these large missing portions of bone on par with autograft materials, design of these materials must include methods to overcome multiple obstacles to effective, efficient bone regeneration. These obstacles include infection and biofilm formation on the biomaterial surface, fibrous tissue formation resulting from ill-fitting implants or persistent inflammation, non-bone tissue formation such as cartilage from improper biomaterial signals to cells, and voids in bone infill or lengthy implant degradation times. Novel biomaterial designs may provide approaches to effectively induce osteogenesis and new bone formation, include design motifs that facilitate surgical handling, intraoperative modification and promote conformal fitting within complex defect geometries, induce a pro-healing immune response, and prevent bacterial infection. In this review, we discuss the bone injury microenvironment and methods of biomaterial design to overcome these obstacles, which if unaddressed, may result in failure of the implant to regenerate host bone.

Fig. 1. Cell types involved in bone homeostasis and during injury and their functions.

Fig. 2. Stages of craniomaxillofacial bone defect regeneration with biomaterial implants and the possible routes of failure. Full regeneration of these defects can occur over the course of years and from the early to late stages of regeneration there are multiple instances of regeneration failure and when any of these failures occur, the biomaterial most likely will need to be removed and regeneration restarted with a new surgery and material.

Fig. 3. Ideal properties of a tissue-engineered scaffold for craniomaxillofacial defect repair. A scaffold should promote new and organized vasculature throughout the defect space in order to delivery nutrients and cells to the newly forming bone. It should also be designed to produce new bone and integrate well with the surrounding bone, doing so by degrading over time and resisting initial resorption by osteoclasts. Finally, a scaffold should prevent infection as chances of this are high in CMF defects, while also guiding the immune response to repair rather than persistent inflammation.

Marley J. Dewey

Brendan A.C. Harley