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A 3D Model of the Effect of Tortuosity and Constrictivity on the Diffusion in Mineralized Collagen Fibril.

ABSTRACT: Bone tissue is a hierarchically structured material composed at the nanoscale by an organic matrix of collagen type I, apatite mineral and water. We considered an idealized 3D geometrical model of the mineralized collagen fibril in order to analyze the influence of structural factors, i.e. tortuosity, constrictivity, on the water effective diffusivity. The average values of the factors investigated in the diffusivity are computed on 5000 iterations by means of the Montecarlo method. The input parameters of the numerical model are the geometrical dimensions of the apatite mineral, collagen fibrils and their spatial orientation obtained with random extractions from Gaussian probability distribution functions. We analyzed the diffusion phenomenon for concentration gradients parallel to three orthogonal directions (Length, Width and Thickness) and for different scenarios, namely low, intermediate and high apatite volume fraction. For each degree of volume fraction, in the thickness direction, the tortuosity assumes greater values, up to two orders of magnitude, in comparison with the tortuous factors computed in the other directions, highlighting the anisotropy of the nanostructure. Furthermore, it was found that the tortuosity is the dominant parameter which control the effective transport properties within the mineralized collagen fibrils.

SUBMITTER: Bini F

PROVIDER: S-EPMC6389916 | 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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A 3D Model of the Effect of Tortuosity and Constrictivity on the Diffusion in Mineralized Collagen Fibril.

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