A highly versatile bioenergetic-active scaffold system for customized orthopedic applications

Abstract

Repairing intractable bone defects, like osteochondral and large segmental defects, remains a huge challenge. Modulating intercellular energy metabolism through biomaterial design to facilitate tissue regeneration represents a breakthrough solution to the above challenge. Herein, we devised a class of highly versatile bioinks and achieved rapid 3D printing of bioenergetic-active scaffolds (BASs) tailored for orthopedic applications. These scaffolds exhibited adaptive mechanical properties and controlled degradation, releasing bioenergetic units that elevate cellular metabolic states, thereby fueling cell differentiation and tissue regeneration. For rabbit osteochondral defects, we fabricated a bioenergetic-active scaffold with a biomimetic gradient interface. Such a scaffold increased subchondral bone regeneration to 220 % of the gradient PCL scaffold and restored high-quality hyaline cartilage with rich type II collagen and typical chondrocyte arrangement, achieving a robust osteochondral interface with compressive strength comparable to that of natural tissue. Regarding large segmental femoral defects in rabbits, a mechanically adaptive bioenergetic-active scaffold was customized and greatly enhanced the diaphysis stability and bone reconstruction, achieving bone bridging across the defects. Therefore, this customizable bioenergetic-active scaffold system successfully addressed the repair of two challenging bone defects without additional growth factors and cells, demonstrating its remarkable versatility and exceptional translational prospects.