Scaffolds composed of polymers and nano-hydroxyapatite (n-HA) have received extensive attention in bone reconstructive repair; however there is a lack of in-depth and long-term comparative study on the effect of scaffold degradability on bone reconstruction. In this study, the osteogenic behaviors of three polymeric composite scaffolds based on fast degradable poly(lactic-co-glycolic acid) (PLGA), slowly degradable polycaprolactone (PCL) and non-degradable polyamide 66 (PA66) were investigated and compared via implanting the scaffolds into rabbit femoral defects for 1, 3, 6 and 12 months. The in vivo results demonstrated that although the n-HA/PLGA scaffold could obtain higher new bone volume at 3 months, its fast degradation caused the loss of scaffold structural integrity and led to reduction of bone volume after 3 months. The n-HA/PCL scaffold displayed slow degradation mainly after 6 months (∼20% degradation) and the n-HA/PA66 scaffold showed no degradation during the entire 12 months; these two scaffolds could maintain their structural integrity and exhibited a constant increase in bone volume with the implantation time, and even achieved higher bone volume than the n-HA/PLGA scaffold at 12 months. The year-long in vivo research revealed the following important aspects: (1) bone reconstruction is strongly related to scaffold degradability, and the scaffold structural integrity should be maintained at least for one year before complete degradation in vivo; (2) the in vivo experiment of a bone scaffold must take more time than the conventional 3 or 6 months, which is normally neglected. The study suggests a principle for future design and application of bone scaffolds that must have a relatively stable osteogenic space and scaffold interface, or have a scaffold degradation speed slower than the time of bone reconstruction completion.

Purpose: The purpose of this study is to construct a guided bone regeneration membrane that is similar to bone components and structurally resembles the native extracellular matrix with sufficient antibacterial properties. Materials and methods: A novel type of biomimetic and bioactive silver ion-loaded calcium phosphate/chitosan (Ag-CaP/CS) membrane with antibacterial ability was successfully developed by incorporation of silver ion-loaded CaP via a one-step electrospinning method and subsequently crosslinked with vanillin. Results: Evaluation of the physicochemical properties revealed that the fabricated fibrous membranes mimicked the extracellular matrix structure and the addition of CaP significantly increased the mineralization ability of the membranes. Importantly, the Ag-CaP/CS membranes exhibited a sustainable release of Ag⁺, which in turn inhibited the adhesion and growth of Staphylococcus mutans. The results of cell adhesion and MTT assay revealed that the Ag-CaP/CS membranes were cytocompatible with bone marrow stromal cells. Conclusion: The fabricated electrospinning Ag-CaP/CS nanofiber membranes with excellent biocompatibility and strong antimicrobial properties have great potential to be used for guided bone regeneration.

We demonstrate a simple, effective and feasible method to address the shrinkage of Poly (lactic-co-glycolic acid) (PLGA) through a core-shell structure fiber strategy. The results revealed that introducing size-stable poly-caprolactone (PCL) as the core fiber significantly improved the PLGA-based fibrous scaffold's dimensional maintenance. We further utilized fish collagen to modify the PLGA shell layer (PFC) of coaxial fibers and loaded baicalin (BA) into the PCL core layer (PCL-BA) to endow fibrous scaffold with more functional biological cues. The PFC/PCL-BA fibrous scaffold promoted the osteogenic differentiation of bone mesenchymal stem cells and stimulated the RAW264.7 cells to polarize into a pro-reparative phenotype. Importantly, the in vivo study demonstrated that the PFC/PCL-BA scaffold could regulate inflammation and osteoclast differentiation, favor neovascularization and bone formation. This work tactfully combined PLGA and PCL to establish a drug release platform based on the core-shell fibrous scaffold for vascularized bone regeneration.