Engineering 3D-Printed Strontium-Titanium Scaffold-Integrated Highly Bioactive Serum Exosomes for Critical Bone Defects by Osteogenesis and Angiogenesis

Currently, healing of large bone defects faces significantchallengessuch as a bulk of bone regeneration and revascularization on the bonedefect region. Here, a cell-free scaffold engineeringstrategy that integrates strontium (Sr) and highly bioactive serumexosomes (sEXOs) inside a three-dimensional (3D)-printed titanium(Ti) scaffold (Sc) is first developed. The constructed SrTi Sc canserve as a sophisticated biomaterial platform for maintaining bonemorphological characteristics of the radius during the period of criticalbone defect (CBD) repair and further accelerating bone formation andfibroblastic suppression via the controlled release of Sr from thesuperficial layer of the scaffold. Moreover, compared with sEXO fromhealthy donors, the sEXO extracted from the serum of the femoral fracturerabbit model at the stage of fracture healing, named BF EXO, is robustlycapable of facilitating osteogenesis and angiogenesis. In addition,the underlying therapeutic mechanism is elucidated, whereby alteringmiRNAs shuttled by BF EXO enables osteogenesis and angiogenesis. Further,the in vivo study revealed that the SrTi Sc + BF EXO composite dramaticallyaccelerated bone repair via osteoconduction, osteoinduction, and revascularizationin radial CBD of rabbits. This study broadens the source and biomedicalpotential of specifically functionalized exosomes and provides a comprehensiveclinically feasible strategy for therapeutics on large bone defects.

Automated summary

A cell-free scaffold engineering strategy that integrates strontium and highly bioactive serum exosomes has been developed for the treatment of large bone defects. The scaffold can maintain bone morphological characteristics and accelerate bone formation through controlled release of strontium, while the serum exosomes extracted from the fracture rabbit model promote osteogenesis and angiogenesis. The SrTi scaffold + BF EXO composite significantly accelerates bone repair in the radial critical bone defect of rabbits.