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Percolation networks inside 3D model of the mineralized collagen fibril.

ABSTRACT: Bone is a hierarchical biological material, characterized at the nanoscale by a recurring structure mainly composed of apatite mineral and collagen, i.e. the mineralized collagen fibril (MCF). Although the architecture of the MCF was extensively investigated by experimental and computational studies, it still represents a topic of debate. In this work, we developed a 3D continuum model of the mineral phase in the framework of percolation theory, that describes the transition from isolated to spanning cluster of connected platelets. Using Monte Carlo technique, we computed overall 120 × 10⁶ iterations and investigated the formation of spanning networks of apatite minerals. We computed the percolation probability for different mineral volume fractions characteristic of human bone tissue. The findings highlight that the percolation threshold occurs at lower volume fractions for spanning clusters in the width direction with respect to the critical mineral volume fractions that characterize the percolation transition in the thickness and length directions. The formation of spanning clusters of minerals represents a condition of instability for the MCF, as it could be the onset of a high susceptibility to fracture. The 3D computational model developed in this study provides new, complementary insights to the experimental investigations concerning human MCF.

SUBMITTER: Bini F

PROVIDER: S-EPMC8166932 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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 Fluffy-PLG (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.

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Percolation networks inside 3D model of the mineralized collagen fibril.

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