Polydopamine-Functionalized Strontium Alginate/Hydroxyapatite Composite Microhydrogel Loaded with Vascular Endothelial Growth Factor Promotes Bone Formation and Angiogenesis

Abstract

Critical-size bone defects are a common and intractable clinical problem that typically requires filling in with surgical implants to facilitate bone regeneration. Considering the limitations of autologous bone and allogeneic bone in clinical applications, such as secondary damage or immunogenicity, injectable microhydrogels with osteogenic and angiogenic effects have received considerable attention. Herein, polydopamine (PDA)-functionalized strontium alginate/nanohydroxyapatite (Sr-Alg/nHA) composite microhydrogels loaded with vascular endothelial growth factor (VEGF) were prepared using microfluidic technology. This composite microhydrogel released strontium ions stably for at least 42 days to promote bone formation. The PDA coating can release VEGF in a controlled manner, effectively promote angiogenesis around bone defects, and provide nutritional support for new bone formation. In in vitro experiments, the composite microhydrogels had good biocompatibility. The PDA coating greatly improves cell adhesion on the composite microhydrogel and provides good controlled release of VEGF. Therefore, this composite microhydrogel effectively promotes osteogenic differentiation and vascularization. In in vivo experiments, composite microhydrogels were injected into criticalsize bone defects in the skull of rats, and they were shown by microcomputed tomography and tissue sections to be effective in promoting bone regeneration. These findings demonstrated that this novel microhydrogel effectively promotes bone formation and angiogenesis at the site of bone defects.

A 3D-printed scaffold composed of Alg/HA/SIS for the treatment of diabetic bone defects

“…Furthermore, the composition of nano-hydroxyapatite can be customized to meet various requirements, thereby broadening its potential applications in bone tissue engineering [ 35 , 43 , 46 ]. For instance, Cheng and coworkers discovered that the functionalization of nano-hydroxyapatite with Sr 2+ significantly promoted osteogenesis and angiogenesis through a process of slow release [ 22 ].…”

“…These findings were aligned with the EDS scan analyses aforementioned, which showed that the highest percentage of calcium element was detected in the Alg/HA/SIS group. Meanwhile, the incorporation of nano-hydroxyapatite particles had also displayed advantages in elevating alkaline phosphatase levels, where some articles had documented the significant role of nano-hydroxyapatite particles in accelerating bone injury healing [ 22 , 42 ]. Furthermore, the composition of nano-hydroxyapatite can be customized to meet various requirements, thereby broadening its potential applications in bone tissue engineering [ 35 , 43 , 46 ].…”

“…However, the biomedical metals such as Ti alloy and synthetical polymers such as poly-ether-ether-ketone are inherently bio-inert, of which the osteogenic performances are not good enough [ 20 ]. Alternatively, biomedical ceramics such as hydroxyapatite are outstanding for their pro-osteogenic function [ 21 , 22 ]. However, the mechanical mismatching between ceramics and natural bones is a knotty problem when the long-standing implants should bear forces in human bodies.…”