3D-printed PLGA-based composite scaffolds for alveolar bone augmentation

Abstract

Alveolar bone loss can happen because of tooth loss, trauma or tumors. In such cases, bone augmentative procedures are needed to restore bone defects/atrophy for further ideal dental implantation. However, alveolar bone augmentation remains a huge challenge because of surgical difficulty, inadequate space maintenance ability and insufficient bone formation. A personalized scaffold with a suitable structure, proper mechanical property and favorable osteogenesis potential is beneficial to solve the problems. Herein, a personalized PLGA/HA/β-TCP (PHT) scaffold with a pre-tapped hole was precisely 3D printed, its physical properties, in vitro and in vivo performances were evaluated. The PHT scaffold demonstrated a well-designed structure that could match perfectly with bone defect areas and the dental implant, and proper mechanical properties as high as 67.18±7.40 MPa in Young’s modulus and 4.85±0.39 MPa in compression stress. Meanwhile, PHT scaffold exhibited favorable in vitro cellular biocompatibility and proper in vivo osteoconductivity in a rabbit bone augmentation model. These results indicated that this pre-tapped-hole PHT scaffold had the potential to reduce the surgical difficulty, provide adequate space maintenance ability for proper bone formation during alveolar bone augmentation procedures. However, bone formation in the PHT scaffold was insufficient and nonuniform partly due to its slow degradation rate, inadequate interconnectivity and limited osteogenesis potential. In the following study, all HA was replaced with β-TCP to allow for an increased degradation rate, interlayer spacing was increased from previous 250 μm to 280 μm for an improved interconnectivity, nanoclay was introduced for better bone formation, and a novel PLGA/β-TCP/nanoclay (PTC) scaffold was 3D printed. Nanoclay as a multifunctional nanomaterial with positive cellular responses has been studied. Herein, the physicochemical properties of the scaffold were determined. The in vitro osteoconductive and osteoinductive properties of the scaffold were assessed by the osteogenic differentiation ability of hBMSCs. The in vitro angiogenesis was reflected using HUVECs. A rabbit calvaria bone augmentation model was applied to evaluate the in vivo bone formation potential. Micro-CT and histology analysis were performed after 12 weeks of implantation. Results indicated that the nanoclay-incorporated PTC scaffold possessed a bio-mimic structure and favorable mechanical properties. The PTC scaffold was more negatively charged and was more inclined to absorb positively charged lysozyme protein under physiological conditions (pH=7.4). Mg, Si ions were steadily released from the PTC scaffold. The negatively charged surface and released ions promoted angiogenesis and osteogenesis in vitro. In the animal study, enhanced angiogenic and osteogenic ability of PTC scaffold were confirmed. These findings suggested that nanoclay-incorporated PTC scaffold could improve bone formation through the promotion of angiogenesis and osteogenesis. Therefore, the PTC scaffold had great potential to reduce the surgical difficulty, provide adequate space maintenance ability for more efficient bone formation during alveolar bone augmentation procedures. Additionally, Sr-BG incorporated PLGA/β-TCP scaffold and gradient porous PLGA/β-TCP scaffold for alveolar bone augmentation were preliminarily studied to explore scaffolds with better clinical applicability and osteogenesis potential. Further studies are needed to be done to confirm their osteogenesis potential and better understand the mechanisms.