Calcium Phosphate Nanocluster-Loaded Injectable Hydrogel for Bone Regeneration

Bone is a hierarchical tissue in which the extracellular matrix consists of hydroxyapatite (HAP) crystals embedded in the collagen matrix. Artificial bone regeneration remains a great challenge due to the difficulty of balancing the chemical composition, biological compatibility, and mechanical performance of the implant. Biomineralization starts from the formation of a hydrogel-like biomacromolecule matrix in many cases, while the mineralization of HAP often builds from amorphous calcium phosphate (ACP) nanoclusters. Inspired by these discoveries, here we use a hydrogel loaded with ∼1 nm sized polymer-stabilized ACP nanoclusters (cluster-loaded hydrogel) as an injectable bone regeneration material. The hydrogel is biocompatible and stabilizes the ACP clusters such that they could efficiently infiltrate into collagen fibrils leading to intrafibrillar mineralization of HAP nanocrystals. Ex vivo results reveal that the cluster-loaded hydrogel has an excellent bone affinity as well as provides a suitable environment for the proliferation and differentiation of bone cells. In vivo experiments with rat bone show that the cluster-loaded hydrogel can generate HAP-based fillings within bone defects with perfect bonding to the surrounding tissue and a mechanical performance comparable with native bone. The fluidity of the hydrogel is further beneficial by providing a feasible minimally invasive bone healing procedure via syringe injection. The discovery and utilization of the cluster-loaded hydrogel described here provide a promising bioinspired approach for bone tissue regeneration.