Inclusion of a 3D-printed Hyperelastic Bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold

Regenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized collagen scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regeneration in vivo . Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized collagen scaffold to improve mechanical and biological activity. Mineralized collagen scaffolds were reinforced with 3D-printed FluffyPLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability of mesenchymal stem cells. Further, inclusion of a mesh formed from Hyperelastic Bone generates a reinforced composite with significantly improved mechanical performance (elastic modulus, push-out strength). Composites formed from the mineralized collagen scaffold and either Hyperelastic Bone or Fluffy-PLG reinforcement both supported human bone-marrow derived mesenchymal stem cell osteogenesis and new bone formation. This was observed by increased mineral formation in Fluffy-PLG composites and increased cell viability and upregulation of RUNX2, Osterix, and COL1A2 genes in both composites. Strikingly, composites reinforced with Hyperelastic Bone mesh elicited significantly increased secretion of osteoprotegerin, a soluble glycoprotein and endogenous inhibitor of osteoclast activity. These results suggest that architectured meshes can be integrated into collagen scaffolds to boost mechanical performance and actively instruct cell processes that aid osteogenicity; specifically, secretion of a factor crucial to inhibiting osteoclast-mediated bone resorption. Future work will focus on further adapting the polymer mesh architecture to confer improved shape-fitting capacity as well as to investigate the role of polymer reinforcement on MSC-osteoclast interactions as a means to increase regenerative potential. Statement of significance Craniofacial bone defects occur due to trauma, congenital abnormalities, and during the course of surgical treatments for stroke and cancer. Clinically-available technologies for craniofacial reconstruction are non-regenerative. We report inclusion of polymer mesh generated via 3D printing into a mineralized collagen scaffold under development for craniofacial bone regeneration. Scaffold-mesh composites improved mechanical performance and mesenchymal stem cell activity, notably secretion of osteoprotegerin, a soluble glycoprotein and endogenous inhibitor of osteoclast activity. These findings suggest the exciting possibility to co-optimize the composition and architecture of an integrated polymer mesh to both passively aid surgical practicality and actively accelerate regenerative healing. (c) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

Incorporating 3D-printed polymer or ceramic-based mesh into mineralized collagen scaffolds improves mechanical and biological activity, supporting mesenchymal stem cell osteogenesis and new bone formation. The mesh can instruct cell processes that aid osteogenicity, specifically inhibiting osteoclast-mediated bone resorption through increased secretion of osteoprotegerin, an endogenous inhibitor of osteoclast activity.