State-of-the-art: A Concept for the Design of Intelligent Biomaterials in Bone Repair

Background At present, there are still problems associated with artificial bone grafting materials, such as shape limitation, inadequate strength, and insufficient biological activity, making it difficult to reach true biological fusion. Moreover, emproving the pathological microenvironment associated with bone defects, characterized by inflammation and osteoporosis, while simultaneously promoting effective bone repair has become a hot research topic in orthopedic bioactive materials.

Methods and Results To address these issues, we have developed multiple biomaterial-bioactive factor carriers and recognition systems to promote bone repair through various mechanisms, such as a chitosan, sodium alginate hydrogel-nano-hydroxyapatite-PTH(1-34) system with biocompatibility and PTH(1-34)-sustained-release ability; an innovative injectable and self-healing hydrogel (GMO hydrogel), which is capable of concurrently delivering osteogenic peptide (KP) and angiogenic peptide (QK); a biomimetic hydroxyapatite (HAp) to coat β-tricalcium phosphate and calcium silicate bio-ceramic to stimulate osteogenic differentiation of BMSCs and facilitate in vivo repair of bone defect. In addition to these advancements, we have designed and synthesized engineered exosomes (CXCR4-miR126-Exo) featuring surface recognition capability for CXCR4, which deliver miRNA to macrophages to alleviate tissue inflammatory response and inhibit bone resorption. We have also constructed a micro-nano mesoporous bioactive glass microsphere-miR-362-3p system to further enhance the uptake and utilization of miRNA by BMSCs, promoting their osteogenic differentiation in an osteoporotic animal model. In order to design biomaterials more specifically, we has focused on the typical biomolecular events, “immunity-metabolism-differentiation” of chondrogenic differentiation in the early stage of fracture, and has screened out important regulatory genes such as NFATc1, which can promote the expression of LRP4 by binding to its promoter region to increase glycolysis of BMSCs and reduces the accumulation of lipid in cells, thereby improving the chondrogenic differentiation ability of BMSCs and promoting endochondral ossification after fracture.

Conclusions Our results have provided a template for the design of bone repair biomaterials in terms of biocompatibility, injectability, self-healing ability and targeting, and have elucidated the “immunity-metabolism-differentiation” mechanism of endochondral ossification during fracture repair, figuring out new directions and approaches for the design of intelligent biomaterials.

Xuenong Zou, a professor in Department of Spinal Surgery, the First Affiliated Hospital of Sun Yat-sen University and the director of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology. Prof. Zou received the Bachelor’s degree(1986) from Jiangxi Medical School and the Master's degree(1994) from Xiangya Medical School. In 2004, Prof. Zou received the Ph.D degree from the Medical School of Aarhus University. In 2008, Prof. Zou has been enrolled in One-Hundred Talent Program of Sun Yat-sen University and recruited as professor by the First Affiliated Hospital of Sun Yat-sen University. His group has been engaging in the interactions between biomaterials and host, the early events and epigenetic mechanisms of bone regeneration, and early detection and regeneration of degenerative intervertebral disc based on extracellular matrix alteration. He has been also interested in the research field of osteoporosis & low back pain. His research is supported by the State Key Program of NSFC, the National Key Basic Research Program (“973” Program) and the Key Program of NSFC-Guangdong Joint Fund, et al. Prof. Zou has published more than 200 academic papers, with H-index 43.