Silk‐Based Bioengineered Diaphyseal Cortical Bone Unit Enclosing an Implantable Bone Marrow toward Atrophic Nonunion Grafting

• Published in: Advanced healthcare materials Vol. 11; no. 6; pp. e2102031 - n/a
• Main Authors: Moses, Joseph Christakiran, Dey, Souradeep, Bandyopadhyay, Ashutosh, Agarwala, Manoj, Mandal, Biman B.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-03-2022
• Subjects: Actuation; Autografts; Bioengineering; Bioglass; Biomedical materials; Bone healing; Bone marrow; bone tissue engineering; CD34 antigen; CD38 antigen; Cell adhesion; cell instructive biomaterials; Cortical bone; Endothelium; engineered bone marrow; Hematopoietic stem cells; Hydroxyapatite; Long bone; Mesenchyme; nonmulberry silk; Nonunion; Orthopedics; Polycaprolactone; Silk fibroin; Stem cells; Substitute bone; Three dimensional printing; Tissue engineering; nonmulberry silk; bone tissue engineering; engineered bone marrow; cell instructive biomaterials; silk fibroin
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202102031

Postnatal fracture healing of atrophic long bone diaphyseal nonunions remains a 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 used in plate reosteosynthesis. Herein, 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, are reported. 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 cross‐talk 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 multimaterial microextrusion bioprinting strategy. Osteogenically primed mesenchymal stem cells‐laden silk fibroin–nano‐hydroxyapatite 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 toward atrophic nonunion repairs.
Bone marrow concentrates alongside autologous spongiosa are clinical interventions used during atrophic nonunions. Paucity of viable autologous bone marrow under compromised conditions necessitates use of alternative tissue engineered solutions. Biofabricated diaphyseal cross‐sectional unit encompassing an engineered bone marrow holds promise in serving as viable bridging‐matrix in plate reosteosynthesis toward atrophic nonunion repair.