Towards the Clinical Translation of 3D PLGA/β-TCP/Mg Composite Scaffold for Cranial Bone Regeneration.

Recent years have witnessed the rapid development of 3D porous scaffolds with excellent biocompatibility, tunable porosity, and pore interconnectivity, sufficient mechanical strength, controlled biodegradability, and favorable osteogenesis for improved results in cranioplasty. However, clinical translation of these scaffolds has lagged far behind, mainly because of the absence of a series of biological evaluations. Herein, we designed and fabricated a composite 3D porous scaffold composed of poly (lactic-co-glycolic) acid (PLGA), β-tricalcium phosphate (β-TCP), and Mg using the low-temperature deposition manufacturing (LDM) technique. The LDM-engineered scaffolds possessed highly porous and interconnected microstructures with a porosity of 63%. Meanwhile, the scaffolds exhibited mechanical properties close to that of cancellous bone, as confirmed by the compression tests. It was also found that the original composition of scaffolds could be maintained throughout the fabrication process. Particularly, two important biologic evaluations designed for non-active medical devices, i.e., local effects after implantation and subchronic systemic toxicity tests, were conducted to evaluate the local and systemic toxicity of the scaffolds. Additionally, the scaffolds exhibited significant higher mRNA levels of osteogenic genes compared to control scaffolds, as confirmed by an in vitro osteogenic differentiation test of MC3T3-E1 cells. Finally, we demonstrated the improved cranial bone regeneration performance of the scaffolds in a rabbit model. We envision that our investigation could pave the way for translating the LDM-engineered composite scaffolds into clinical products for cranial bone regeneration.