3D生物打印仿生骨膜：从结构替代到功能整合

doi:10.3969/j.issn.1674-8115.2026.09.002

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (9): 1169-1178.doi: 10.3969/j.issn.1674-8115.2026.09.002

• 前沿述评 • 上一篇

3D生物打印仿生骨膜：从结构替代到功能整合

余美萱¹, 孙林²^,³, 符静珂²^,³^,^#(), 郝永强²^,³^,⁴^,⁵^,⁶^,^#(), 戴尅戎²^,³^,⁴^,⁵^,⁶

^1.复旦大学附属中山医院眼科，上海 200032
^2.上海交通大学医学院附属第九人民医院骨科，上海 200011
^3.上海交通大学医学3D打印创新研究中心，上海 200011
^4.上海市医学3D打印技术临床转化工程研究中心，上海 200011
^5.上海骨科创新器械与个性化医学工程技术研究中心，上海 200011
^6.数字医学教育部工程研究中心，上海 200011

收稿日期:2026-01-12 接受日期:2026-02-09 出版日期:2026-09-28 发布日期:2026-09-28
通讯作者: 符静珂，副研究员，博士；电子信箱：fujingke@sjtu.edu.cn。
郝永强，主任医师，博士；电子信箱：hao_yongqiang@hotmail.com。
作者简介:第一联系人：为共同通信作者。
基金资助:
国家自然科学基金面上项目(82273489);上海交通大学医学院生物材料与再生医学研究院联合攻关项目(2022LHA09)

3D printing biomimetic periosteum: from structural substitution to functional integration

Yu Meixuan¹, Sun Lin²^,³, Fu Jingke²^,³^,^#(), Hao Yongqiang²^,³^,⁴^,⁵^,⁶^,^#(), Dai Kerong²^,³^,⁴^,⁵^,⁶

^1.Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
^2.Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
^3.Shanghai Jiao Tong University Medical 3D Printing Innovation Research Center, Shanghai 200011, China
^4.Shanghai Engineering Research Center of Clinical Translation of Medical 3D Printing Technology, Shanghai 200011, China
^5.Shanghai Engineering Research Center of Innovative Orthopedic Devices and Personalized Medicine, Shanghai 200011, China
^6.Engineering Research Center of Digital Medicine, Ministry of Education, Shanghai 200011, China

Received:2026-01-12 Accepted:2026-02-09 Online:2026-09-28 Published:2026-09-28
Contact: Fu Jingke, E-mail: fujingke@sjtu.edu.cn.
Hao Yongqiang, E-mail: hao_yongqiang@hotmail.com.
Supported by:
General Program of National Natural Science Foundation of China(82273489);Joint Research Project of Institute of Biomaterials and Regenerative Medicine, Shanghai Jiao Tong University School of Medicine(2022LHA09)

摘要/Abstract

摘要：

骨膜作为骨再生的核心调控屏障，通过提供成骨前体细胞和多种生物活性因子主导骨修复进程，其功能缺失是骨缺损修复失败的关键因素。传统骨膜重建方法难以精确再现骨膜的精细层级结构与多元生物学功能，限制了其临床应用。3D打印技术具备个性化结构精准成型、多尺度微结构高度可控及生物活性组分时空有序递送等独特优势，为仿生骨膜的构建提供了具有变革意义的解决方案。当前临床主流骨修复手段及传统骨膜构建技术均存在短板，无法有效解决大面积骨缺损的修复难题。随着再生医学精准化发展，仿生骨膜的研发理念已从单一结构填充的结构替代，逐步转向多维度生理复刻、修复微环境动态调控的功能整合新阶段。该文系统梳理了骨膜的核心生物学功能及临床需求，重点探讨3D打印仿生骨膜的关键构建策略及多工艺融合路径，深入分析当前技术瓶颈，并展望人工智能驱动下骨膜重建向个性化精准修复范式转型的未来方向，旨在为大面积骨缺损修复的临床转化及精准医疗发展提供理论依据与实践参考。

关键词: 仿生骨膜, 骨重建, 3D打印技术, 4D生物打印, 多工艺融合

Abstract:

The periosteum, as the central regulatory barrier for bone regeneration, directs bone repair by supplying osteogenic progenitor cells and diverse bioactive factors; its functional loss is a key reason for the failure of bone defect repair. Conventional periosteal reconstruction methods are markedly limited in clinical practice because they cannot precisely recapitulate the periosteum′s refined hierarchical architecture and multifaceted biological functions. Leveraging its unique strengths in patient-specific high-fidelity shaping, tightly controlled multiscale microarchitectures, and spatiotemporally ordered delivery of bioactive components, 3D printing offers a transformative solution for constructing biomimetic periosteum. Both mainstream clinical bone repair therapies and traditional periosteum fabrication techniques have inherent drawbacks and fail to address the clinical challenge of large bone defect repair effectively. With the advancement of precision regenerative medicine, the developmental philosophy of biomimetic periosteum has shifted from simple structural substitution based on simple defect filling to a new stage of functional integration, characterized by multidimensional physiological simulation and dynamic modulation of the repair microenvironment. This review systematically outlines the periosteum′s core biological functions and clinical needs, focuses on key construction strategies and multi-technology integration pathways for 3D-printed biomimetic periosteum, provides an in-depth analysis of current technical bottlenecks, and envisions an artificial intelligence-driven shift of periosteal reconstruction toward a paradigm of personalized, precision repair. The goal is to provide a theoretical basis and practical reference for the clinical translation of therapies for large bone defects and the development of precision medicine.

Key words: biomimetic periosteum, osseous reconstruction, 3D printing technology, 4D bioprinting, multi-technology integration

中图分类号:

R684.3

余美萱, 孙林, 符静珂, 郝永强, 戴尅戎. 3D生物打印仿生骨膜：从结构替代到功能整合[J]. 上海交通大学学报（医学版）, 2026, 46(9): 1169-1178.

Yu Meixuan, Sun Lin, Fu Jingke, Hao Yongqiang, Dai Kerong. 3D printing biomimetic periosteum: from structural substitution to functional integration[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026,(9): 1169-1178.

图/表 3

参考文献 58

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Manufacturing	Model	Biomaterial in bioinks	OFC in bioinks	Main effect	Reference
EBP	Rat cranial defect	Fibrous layer: SFHGMA, SA Formation layer: SFP, SA, MCol	Mg²⁺	Simulation of natural periosteal double-layer structure; promotion of cell proliferation and differentiation, angiogenesis, and PC12 cell growth	[29]
EBP	Regeneration of critical-sized bone defects in long bones	GelMA	G-MBGN, VEGF-loaded liposomes	Simulation of periosteum, endosteum, and intermediate bone matrix; significant promotion of angiogenesis	[39]
EBP	Critical-sized bone defect	Formation layer: GelMA, GelMA-H-nHA Fibrous layer: P(ACG-GelMA-L)-Mg²⁺	Ca²⁺, Mg²⁺, nHA	Simulation of natural periosteal double-layer structure, with Mg²⁺-mediated immunomodulation and angiogenesis	[30]
EBP	Bone defect	PLLA/HA, GelMA	rabBMSCs, rabPDSCs	Excellent cell encapsulation and bioactivity; co-culture of BMSCs and PDSCs	[31]
EBP	Bone defect	GelMA, SilMA, GelDA	GO nanosheets, BMSCs	Excellent thermosensitivity and printability; high cell viability and adhesion	[40]
MEW	Critical-sized segmental rat femoral defect	MEW core: PCL FDM Shell: PCL Coating: nnHA	BMP2	High rigidity, structural integrity, sustained BMP2 release, and significant angiogenesis enhancement	[32]
MEW	Large bone defect	PCL membrane, PCL sheet	rhBMP-2, PLGA-PEG-COOH microparticles	Controlled rhBMP-2 release and significant enhancement of in vivo bone regeneration	[35]
SLA	Bone defect	Fibrous layer: PEGDA, TCP Formation layer: GelMA, PEGDA	Mo, Chitosan	Fibrous layer resistance to muscle traction and soft tissue invasion; promotion of osteogenic differentiation by the formation layer	[33]

Manufacturing	Model	Biomaterial in bioinks	OFC in bioinks	Main effect	Reference
EBP	Rat cranial defect	Fibrous layer: SFHGMA, SA Formation layer: SFP, SA, MCol	Mg²⁺	Simulation of natural periosteal double-layer structure; promotion of cell proliferation and differentiation, angiogenesis, and PC12 cell growth	[29]
EBP	Regeneration of critical-sized bone defects in long bones	GelMA	G-MBGN, VEGF-loaded liposomes	Simulation of periosteum, endosteum, and intermediate bone matrix; significant promotion of angiogenesis	[39]
EBP	Critical-sized bone defect	Formation layer: GelMA, GelMA-H-nHA Fibrous layer: P(ACG-GelMA-L)-Mg²⁺	Ca²⁺, Mg²⁺, nHA	Simulation of natural periosteal double-layer structure, with Mg²⁺-mediated immunomodulation and angiogenesis	[30]
EBP	Bone defect	PLLA/HA, GelMA	rabBMSCs, rabPDSCs	Excellent cell encapsulation and bioactivity; co-culture of BMSCs and PDSCs	[31]
EBP	Bone defect	GelMA, SilMA, GelDA	GO nanosheets, BMSCs	Excellent thermosensitivity and printability; high cell viability and adhesion	[40]
MEW	Critical-sized segmental rat femoral defect	MEW core: PCL FDM Shell: PCL Coating: nnHA	BMP2	High rigidity, structural integrity, sustained BMP2 release, and significant angiogenesis enhancement	[32]
MEW	Large bone defect	PCL membrane, PCL sheet	rhBMP-2, PLGA-PEG-COOH microparticles	Controlled rhBMP-2 release and significant enhancement of in vivo bone regeneration	[35]
SLA	Bone defect	Fibrous layer: PEGDA, TCP Formation layer: GelMA, PEGDA	Mo, Chitosan	Fibrous layer resistance to muscle traction and soft tissue invasion; promotion of osteogenic differentiation by the formation layer	[33]

Multi-technology integration	Biomaterial in ink	Bioactive substance in ink	Highlight	Reference
Electrospinning+3D printing	Electrospun collagen-dense scaffold, IMCS	BMSCs	Upper-layer blockade of fibrous tissue invasion; lower-layer promotion of BMSC osteogenic differentiation	[49]
IMT+3D printing	mPCL-TCP	ABG, rhBMP-2, Cerament G^®, Cerament V^®	Excellent clinical adaptability, superior surgical manoeuvrability, and enhanced angiogenesis and osteogenesis	[50]
IMT+3D printing	PLA scaffold, dECM	Bone marrow cells, BMP-2	High-dose, sustained release of BMP-2; reduced fibrosis and macrophage infiltration; optimized BMP-2 loading capacity	[51]

Multi-technology integration	Biomaterial in ink	Bioactive substance in ink	Highlight	Reference
Electrospinning+3D printing	Electrospun collagen-dense scaffold, IMCS	BMSCs	Upper-layer blockade of fibrous tissue invasion; lower-layer promotion of BMSC osteogenic differentiation	[49]
IMT+3D printing	mPCL-TCP	ABG, rhBMP-2, Cerament G^®, Cerament V^®	Excellent clinical adaptability, superior surgical manoeuvrability, and enhanced angiogenesis and osteogenesis	[50]
IMT+3D printing	PLA scaffold, dECM	Bone marrow cells, BMP-2	High-dose, sustained release of BMP-2; reduced fibrosis and macrophage infiltration; optimized BMP-2 loading capacity	[51]

3D生物打印仿生骨膜：从结构替代到功能整合

3D printing biomimetic periosteum: from structural substitution to functional integration

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