Biology subjects

Nosatov, A. V.

Publications and source records attributed to Nosatov, A. V..

3 recordsLinked to original sources

bioRxiv2023

Generative design approach to combine architected Voronoi foams with porous collagen scaffolds to create a tunable composite biomaterial

Regenerative biomaterials for musculoskeletal defects must address multi-scale mechanical challenges. We are developing biomaterials for craniomaxillofacial bone defects that are often large and irregularly shaped. These require close conformal contact between implant and defect margins to aid healing. While we have identified a mineralized collagen scaffold that promotes mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo, its mechanical performance is insufficient for surgical translation. We report a generative design approach to create scaffold-mesh composites by embedding a macro-scale polymeric Voronoi mesh into the mineralized collagen scaffold. The mechanics of architected foam reinforced composites are defined by a rigorous predictive moduli equation. We show biphasic composites localize strain during loading. Further, planar and 3D mesh-scaffold composites can be rapidly shaped to aid conformal fitting. Voronoi-based composites overcome traditional porosity-mechanics relationship limits while enabling rapid shaping of regenerative implants to conformally fit complex defects unique for individual patients.

bioengineering↗

bioRxiv2020

Inclusion of a polylactide-co-glycolide co-polymer mesh enhances osteogenesis in mineralized collagen scaffolds

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. 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.

bioengineering↗

bioRxiv2020

Anisotropic mineralized collagen scaffolds accelerate osteogenic response in a glycosaminoglycan-dependent fashion

Regeneration of critically-sized craniofacial bone defects requires a template to promote cell activity and bone remodeling. However, induced regeneration becomes more challenging with increasing defect size. Methods of repair using allografts and autografts have inconsistent results, attributed to age-related regenerative capabilities of bone. We are developing a mineralized collagen scaffold to promote craniomaxillofacial bone regeneration as an alternative to repair. Here, we hypothesize modifying the pore anisotropy and glycosaminoglycan content of the scaffold will improve cell migration, viability, and subsequent bone formation. Using anisotropic and isotropic scaffold variants, we test the role of pore orientation on human mesenchymal stem cell (MSC) activity. We subsequently explore the role of glycosaminoglycan content, notably chondroitin-6-sulfate, chondroitin-4-sulfate, and heparin sulfate on mineralization. We find that while short term MSC migration and activity was not affected by pore orientation, increased bone mineral synthesis was observed in anisotropic scaffolds. Further, while scaffold glycosaminoglycan content did not impact cell viability, heparin sulfate and chondroitin-6-sulfate containing variants increased mineral formation at the late stage of in vitro culture, respectively. Overall, these findings show scaffold microstructural and proteoglycan modifications represent a powerful tool to improve MSC osteogenic activity.

bioengineering↗