Journal of Zhejiang University

Bio-Design and Manufacturing 2026 Vol.9 No.5 P.1001 - 1022

Ti6Al4V/Xenogeneic bone composite promotes osseointegration by recapitulating the osteogenic microenvironment

Author(s): Xiang Yue,Wenbo Yang,Hao Chen,Xiaofan Gao,Jing Shang,Lanfeng Song,Shipu Jia,Lanqing Cao,Shiwei Lu,Rui Yao,Yuchi Fang,Fangbin Deng,Qing Han,Xin Zhao,Jincheng Wang,Haotian Bai
Affiliation(s): 1. Department of Orthopedic Surgery, The Second Norman Bethune Hospital of Jilin University, Changchun 130000, China more
Corresponding email(s): baihaotian@jlu.edu.cn
Key Words: Bone tissue engineering, Osseointegration, Demineralized-decellularized bone matrix, Ti6Al4V scaffold, Composite, Osteogenic microenvironment

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Xiang Yue, Wenbo Yang, Hao Chen, Xiaofan Gao, Jing Shang, Lanfeng Song, Shipu Jia, Lanqing Cao, Shiwei Lu, Rui Yao, Yuchi Fang, Fangbin Deng, Qing Han, Xin Zhao, Jincheng Wang, Haotian Bai. Ti6Al4V/Xenogeneic bone composite promotes osseointegration by recapitulating the osteogenic microenvironment[J]. Journal of Zhejiang University Science D, 2026, 9(5): 1001 - 1022.

@article{title="Ti6Al4V/Xenogeneic bone composite promotes osseointegration by recapitulating the osteogenic microenvironment",
author="Xiang Yue, Wenbo Yang, Hao Chen, Xiaofan Gao, Jing Shang, Lanfeng Song, Shipu Jia, Lanqing Cao, Shiwei Lu, Rui Yao, Yuchi Fang, Fangbin Deng, Qing Han, Xin Zhao, Jincheng Wang, Haotian Bai",
journal="Journal of Zhejiang University Science D",
volume="9",
number="5",
pages="1001 - 1022",
year="2026",
publisher="Zhejiang University Press & Springer",
doi="10.1631/bdm.2600008"
}

%0 Journal Article
%T Ti6Al4V/Xenogeneic bone composite promotes osseointegration by recapitulating the osteogenic microenvironment
%A Xiang Yue
%A Wenbo Yang
%A Hao Chen
%A Xiaofan Gao
%A Jing Shang
%A Lanfeng Song
%A Shipu Jia
%A Lanqing Cao
%A Shiwei Lu
%A Rui Yao
%A Yuchi Fang
%A Fangbin Deng
%A Qing Han
%A Xin Zhao
%A Jincheng Wang
%A Haotian Bai
%J Journal of Zhejiang University SCIENCE D
%V 9
%N 5
%P 1001 - 1022
%@ 1869-1951
%D 2026
%I Zhejiang University Press & Springer
%DOI 10.1631/bdm.2600008

TY - JOUR
T1 - Ti6Al4V/Xenogeneic bone composite promotes osseointegration by recapitulating the osteogenic microenvironment
A1 - Xiang Yue
A1 - Wenbo Yang
A1 - Hao Chen
A1 - Xiaofan Gao
A1 - Jing Shang
A1 - Lanfeng Song
A1 - Shipu Jia
A1 - Lanqing Cao
A1 - Shiwei Lu
A1 - Rui Yao
A1 - Yuchi Fang
A1 - Fangbin Deng
A1 - Qing Han
A1 - Xin Zhao
A1 - Jincheng Wang
A1 - Haotian Bai
J0 - Journal of Zhejiang University Science D
VL - 9
IS - 5
SP - 1001
EP - 1022
%@ 1869-1951
Y1 - 2026
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/bdm.2600008

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Ti6Al4V implants are used to repair critical-sized bone defects, but their bioinert surfaces often cause insufficient early osteogenic stimulation, potentially leading to compromised long-term fixation. The osteogenic microenvironment is vital for osseointegration between the host bone and the implant and influences long-term clinical outcomes. Consequently, researchers have attempted to mimic the natural osteogenic microenvironment using microporous design, physical and chemical modification, and loading of bioactive factors. The present study proposes a strategy for fully recapitulating the natural osteogenic microenvironment within microporous Ti6Al4V implants. First, Ti6Al4V scaffolds were implanted into rat femoral condyle defects to establish osseointegration. The resulting construct was then demineralized and decellularized to produce an implantable Ti6Al4V/xenogeneic bone composite. Pull-out tests demonstrated that the bone tissue remained well-integrated with the scaffold after processing. Nucleic acid detection and galactose-α-1,3-galactose (α-Gal) analysis verified the elimination of immunogenicity in the composite. Immunofluorescence staining for bone morphogenetic protein-2 and transforming growth factor-β confirmed the preservation of key bioactive factors. In vitro cell experiments revealed favorable biocompatibility and osteoinductive activity. When implanted into rabbit femoral condyle defects, the composite significantly enhanced bone ingrowth into the microporous Ti6Al4V implant and strengthened osseointegration. Histological and quantitative analyses further showed that the composite shifted the osteogenic pattern from the osteoconduction-dominant mode characteristic of Ti6Al4V implants to an osteoinduction-dominant pattern of bone formation. In summary, we developed a novel Ti6Al4V/ xenogeneic bone composite that fully recreated the natural osteogenic microenvironment. This composite effectively improved the osseointegration capacity of conventional scaffolds and demonstrated considerable potential for clinical application.

Ti6Al4V/异种骨复合材料通过重现成骨微环境促进骨整合

Ti6Al4V 植入物已被广泛应用于临界尺寸骨缺损的修复。然而，其表面生物惰性较强，往往难以在植入早期提供充分的成骨刺激，进而可能影响远期固定效果。宿主骨与植入物之间的成骨微环境是实现骨整合的关键因素，并对长期临床结局具有重要影响。因此，研究者尝试通过微孔结构设计、物理化学表面改性及负载生物活性因子等方法模拟天然成骨微环境。本研究提出了一种在微孔Ti6Al4V 植入物内部完整重建天然成骨微环境的策略。首先，将 Ti6Al4V 支架植入大鼠股骨髁骨缺损区以建立骨整合。在此基础上，对所得复合结构进一步进行脱钙和脱细胞处理，制备得到可移植的 Ti6Al4V/异种骨复合材料。拔出力实验表明，经处理后骨组织仍与支架保持良好的整合状态。核酸检测及 α-Gal 分析证实，BMP-2 和 TGF-β 免疫荧光染色结果显示，该复合材料的免疫原性已被有效去除。关键生物活性因子得以保留。体外细胞实验进一步表明，该复合材料具有良好的生物相容性和成骨诱导活性。将其植入兔股骨髁骨缺损后，复合材料显著促进骨组织向微孔 Ti6Al4V 植入物内部生长，并增强了骨整合效果。组织学观察及定量分析进一步表明，该复合材料使 Ti6Al4V 植入物原本以骨传导为主的成骨模式转变为以骨诱导为主的成骨模式。综上，本研究构建了一种新型 Ti6Al4V/异种骨复合材料，可较为完整地重建天然成骨微环境。该复合材料能够有效提升常规Ti6Al4V 支架的骨整合能力，具有较大的临床应用潜力。
关键词：骨组织工程；骨整合；脱钙-脱细胞骨基质；Ti6Al4V 支架；复合材料；成骨微环境