Silk Based Bioengineered Diaphyseal Cortical Bone Unit Enclosing An Implantable Bone Marrow Towards Atrophic Non-union Grafting.

Postnatal fracture healing of atrophic long bone diaphyseal nonunions poses a great challenge for orthopedic surgeons. Paucity of autologous spongiosa has potentiated the use of tissue engineered bone grafts to improve success rates of bone marrow engraftment frequently used in plate reosteosynthesis. In this work we report the development and in vitro validation of a "sandwich type" biofabricated diaphyseal cross-sectional unit, with an outer mechanically robust bioprinted cortical bone shell, encompassing an engineered bone marrow. Channelized silk fibroin blend sponges derived from Bombyx mori and Antheraea assama help in developing compartmentalized endosteum, exhibiting specialized osteoblasts (endosteal niche) and discontinuous endothelium (vascular niche). The cellular crosstalk between these two niches triggered via integrin-mediated cell adhesion, enables in preserving quiescence state of CD34+ /CD38- hematopoietic stem cells and their recycling in the engineered marrow. The outer cortical bone strut is developed through multi-material micro-extrusion bioprinting strategy. Osteogenically primed mesenchymal stem cells-laden silk fibroin-nano hydroapatite bioink is bioprinted alongside paramagnetic Fe-doped bioactive glass-polycaprolactone blend thermoplastic ink, reinforcing it for mechanical stability. Pulsed magnetic field actuation positively influences the osteogenic commitment and maturation of the bioprinted constructs via mechanotransductory route. Therefore, the assembled engineered marrow and bioprinted cortical shell hold promise as potential orthobiologic substitutes towards atrophic non-union repairs. This article is protected by copyright. All rights reserved.