文献类型：期刊文献

英文题名：Development-based In Vivo Bioreactor Strategy for Challenging Senescent Bone Reconstruction

作者：Zhang, Wenchao[1,2];Dai, Kai[1,2,3];Shen, Tong[1,2];Gao, Zehua[1,2];Yan, Fengying[1,2];Feng, Yuke[1,2];Wang, Xuanlin[1,2];Zhang, Shaozhen[1,2];Wang, Jing[1,2,3];Liu, Changsheng[2,3,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Engn Res Ctr Biomed Mat, Minist Educ, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai, Peoples R China;[4]East China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Shanghai, Peoples R China

年份：2026

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20261120249188);WOS:【SCI-EXPANDED(收录号:WOS:001708901400001)】；

基金：The Basic Science Center Program (No. T2288102) the National Natural Science Foundation of China (No. 32230059), the National Natural Science Foundation of China (No. 32471406), the National Natural Science Foundation of China (No. 32301123), the National Natural Science Foundation of China (No. 32571564), the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry (No. JKVD1211002), Key Research and Development Plan of Shandong Province (2023CXPT103) and the Foundation of National Center for Translational Medicine (Shanghai) SHU Branch (No. SUITM-202403). We thank the staff members of the Integrated Laser Microscopy System at the National Facility for Protein Science in Shanghai, for providing technical support and assistance in data collection and analysis. We thank W. Xue at ECUST for assistance with schematic illustrations of animal models.

语种：英文

外文关键词：in vivo bioreactor; developmental engineering; segmental bone defect; aging

摘要：Critical segmental bone defects in elderly patients pose a formidable clinical challenge due to limited autograft availability, senescent bone dysfunction, and compromised healing from fibrous tissue invasion. Here, we present a development-based in vivo bioreactor strategy wherein BMP-2-loaded biomaterials trigger the body's intrinsic developmental programs, using the organism as a bioreactor to engineer bone. Distinct from classical developmental engineering, this in vivo bioreactor-derived bone (vBR-Bone) recapitulates native osseous architecture, including vasculature, cortical bone, trabeculae, and bone marrow niche. In aged murine models, the vBR-Bone exhibits a rejuvenated restoration of bone bioactivity lost in aging, with reduced senescence, elevated remodeling, and improved stem cell functionality. Capitalizing on its restored remodeling capacity of high bone turnover, the vBR-Bone fragments enclosed in an asymmetric biomimetic periosteum achieved 6-week repair of critical-sized 1/3 femoral shaft segmental defects. Through a "compartmentalized" approach that partitions the defect into manageable fragments, vBR-Bone progressively remodeled and integrated into functional trabecular bone, ultimately restoring bone mineral density, volume, and microstructure in defects of aged mice. The biomimetic periosteum inhibits fibrous invasion while permitting vascular ingrowth, thereby creating a space for regeneration. Mechanistically, the multifactors within vBR-Bone reconstitute a bone-remodeling microenvironment, wherein matrix-released TGF-beta 1 activates the PI3K/AKT/mTOR signaling axis via TRAF6-dependent ubiquitylation to promote robust osteogenesis. This strategy overcomes autograft shortage and senescence-associated dysfunction, offering a clinically translatable solution for critical age-related segmental bone defects.