Mineralization in micropores of calcium phosphate scaffolds

With the increasing demand for novel bone repair solutions that overcome the drawbacks of current grafting techniques, the design of artificial bone scaffolds is a central focus in bone regeneration research. Calcium phosphate scaffolds are interesting given their compositional similarity with bone mineral. The majority of studies focus on bone growth in the macropores (>100 µm) of implanted calcium phosphate scaffolds where bone structures such as osteons and trabeculae can form. However, a growing body of research shows that micropores (<50 µm) play an important role not only in improving bone growth in the macropores, but also in providing additional space for bone growth. Bone growth in the micropores of calcium phosphate scaffolds offers major mechanical advantages as it improves the mechanical properties of the otherwise brittle materials, further stabilizes the implant, improves load transfer, and generally enhances osteointegration. In this paper, we review evidence in the literature of bone growth into micropores, emphasizing on identification techniques and conditions under which bone components are observed in the micropores. We also review theories on mineralization and propose mechanisms, mediated by cells or not, by which mineralization may occur in the confined micropore space of calcium phosphate scaffolds. Understanding and validating these mechanisms will allow to better control and enhance mineralization in micropores to improve the design and efficiency of bone implants. STATEMENT OF SIGNIFICANCE: The design of synthetic bone scaffolds remains a major focus for engineering solutions to repair damaged and diseased bone. Most studies focus on the design of and growth in macropores (>100 µm), however research increasingly shows the importance of microporosity (<50 µm). Micropores provide an additional space for bone growth, which provides multiple mechanical advantages to the scaffold/bone composite. Here, we review evidence of bone growth into micropores in calcium phosphate scaffolds and conditions under which growth occurs in micropores, and we propose mechanisms that enable or facilitate growth in these pores. Understanding these mechanisms will allow researchers to exploit them and improve the design and efficiency of bone implants.