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

Abstract

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 copolymer) 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.

Application of a Hyperelastic 3D Printed Scaffold for Mesenchymal Stem Cell-Based Fabrication of a Bizonal Tendon Enthesis-like Construct

“…The structural core of our construct is a scaffold composed of medical-grade PLGA, with high internal porosity and elastic properties sufficient to form a self-supporting mesh (Dewey et al, 2020), and able to support cell viability and proliferation (Jakus et al, 2018). Furthermore, the scaffold has been previously reported to be cytocompatible and supportive of MCSs differentiation both in vitro and in mouse and macaque in vivo models (Jakus et al, 2016).…”

“…hMSCs represent a good choice to promote de novo regeneration, owing to their relative abundant availability and to their differentiation potential into all cellular phenotypes of the musculoskeletal lineage (Nancarrow-Lei et al, 2017). The structural core of our construct is a scaffold composed of medical-grade poly (L-lactide-co-glycolide) (PLGA), with high internal porosity and elastic properties sufficient to form a selfsupporting mesh (Dewey et al, 2020), and able to support cell proliferation (Jakus et al, 2018). The pore architecture was specified for each tissue-type with changes in both dimension and distribution, smaller and aligned at the tendon side to favor the aligned deposition of collagen fibers, and larger and more randomly distributed at the cartilaginous side to mimic the architecture of cartilage.…”

Mimicking the Hierarchical Organization of Natural Collagen: Toward the Development of Ideal Scaffolding Material for Tissue Regeneration

“…Actually, autograft is the gold standard for repairing defective tissue, but it may lead to donor tissue degeneration and dysfunction (Ma et al, 2021). However, the limited access to autologous bone, donor site morbidity, surgical complications, fitting irregular defect difficulties, as well as inconsistent repair limited its execution (Dewey et al, 2021). On the other side, allotransplantation can cause immune rejection (Ma et al, 2021).…”

“…Recently, 3D printing and the annex potential of computeraided design and computer-aided manufacturing (CAD-CAM) technology in scaffold according to patient-specific bone defect were investigated (Bahraminasab, 2020). Several biomaterials were printed in blend with collagen such as hydroxyapatite (Keriquel et al, 2017), β tricalcium-phosphate (Bian et al, 2012), polycaprolactone (PCL) (Ciocca et al, 2014), poly(lactide-co-glycolide) (PLGA) (Dewey et al, 2021) in order to improve temporal substitutes' mechanical strength (Bahraminasab, 2020). Although having promising outcomes, 3D technology is still far from transforming research knowhow into clinical products.…”

Biomaterial design strategies to address obstacles in craniomaxillofacial bone repair

“…Many novel materials developed currently, include hydroxyapatite coatings 47,60 and metal or ceramics particles 45,46,[53][54][55]75 incorporated into polymeric base materials to increase mechanical stability and osteogenesis. 79,82,85,86,89 Other unique promising approaches include bone-mimicking structural elements as well as composition, such as the use of Voronoi opencell architectures to replicate the porosity and mechanical structure of cortical and cancellous bone, 87 and 3D-printing haversian canals to better transport multiple cells and nutrients throughout the entire implant. 88 Composites represent a new way to use existing materials to improve mechanics and biological performance, as well as avoid many of the drawbacks of these materials.…”