journal article·2026-05-21Open access

Multi‐Omics Profiling Reveals Immunomodulatory and Pro‐Regenerative Effects of a Graphene Oxide–Collagen Scaffold in Massive Rotator Cuff Tears

Renwen Wan, Yechuan Deng, Zixin Hu, Yanwei He, Xinting Feng, Jun Ma, Yisheng Chen, Zhijie Zhao, Jie Mei, Zhiheng Lin, Wei Luo, Zhengyuan Fang, Zhufeng Hu, Kunlun Feng, Xinrong Li, Dan Wu, Bowen Han, James Hoi po Hui, Xuanyong Liu, Chen Chen, Gang Chen, Shiyi Chen, Nirong Bao, Jiajun Qiu, Zhiwen Luo

Abstract

ABSTRACT Massive rotator cuff tears (MRCT) remain a clinical challenge, characterized by poor tendon‐bone interface (TBI) healing, severe muscle degeneration, and high postoperative retear rates. Tissue engineering scaffolds offer promising alternatives, yet traditional biomaterials often lack sufficient bioactivity to orchestrate comprehensive tissue regeneration. Herein, we developed a novel graphene oxide (GO)‐engineered porcine type I collagen (GO/Col) scaffold and systematically investigated its therapeutic efficacy and underlying molecular mechanisms via multi‐omics analyses. Comprehensive characterization showed that GO incorporation improved scaffold stability, wettability, and biocompatibility. In vitro, the GO/Col scaffold enhanced mesenchymal stem cell adhesion and proliferation, promoted osteogenic and chondrogenic differentiation, and suppressed adipogenesis. In a macrophage model system, GO/Col was associated with a shift toward a more reparative, anti‐inflammatory phenotype. Using a clinically relevant chronic MRCT rat model, we observed that GO/Col scaffolds significantly improved motor function, biomechanical properties, and tendon‐bone regeneration, while inhibiting muscle fibrosis and fatty infiltration. Mechanistically, integrated transcriptomics, proteomics, and mass cytometry analyses revealed GO‐mediated modulation of critical signaling pathways involved in immune regulation, stem cell differentiation, and tissue regeneration. Notably, GO activated pro‐osteogenic/chondrogenic pathways and anti‐inflammatory signatures, while downregulating adipogenic and pro‐inflammatory pathways. Collectively, these findings support the potential of GO/Col scaffolds as a bioactive tissue‐engineering strategy for chronic MRCT repair.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Tendon Structure and Treatment · Graphene and Nanomaterials Applications · Electrospun Nanofibers in Biomedical Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Sports Medicine Huashan Hospital Fudan University Shanghai China

Department of Orthopaedics Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials The Second Affiliated Hospital of Jiaxing University (Sports Hospital of Jiaxing) Jiaxing P. R. China

Fudan University – Dr. Kong Joint Research Center for Sports Medicine and Health Footwear Fudan University Institute of Sports Medicine (Jinqiao Laboratory) Shanghai China

State Key Laboratory of High Performance Ceramics Shanghai Institute of Ceramics Chinese Academy of Sciences Shanghai China

Artificial Intelligence Innovation and Incubation Institute Fudan University Shanghai China

Shanghai Academy of Artificial Intelligence for Science Shanghai China

Ningde Municipal Hospital Ningde Normal University Ningde Fujian China

Fujian Medical University Ningde Fujian China

Fujian Key Laboratory of Toxicant and Drug Toxicology Medical College, Ningde Normal University Ningde Fujian China

Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China

The First Clinical Medicine College Nanjing Medical University Nanjing China

Department of Gynecology Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai China

Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine Shanghai Jiao Tong University Shanghai China

Department of Integrative Medicine Huashan Hospital Fudan University Shanghai China

Department of Orthopedics Zhongda Hospital Southeast University Nanjing China

Department of Acupuncture and Moxibustion Yueyang Hospital of Integrated Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Shanghai China

Department of Orthopaedic Surgery Yong Loo Lin School of Medicine National University of Singapore Singapore

Department of Arthroscopic Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China

Department of Orthopedics, Ward 5, 11th Floor, Surgery Building Nanjing Jinling Hospital Affiliated Hospital of Medical School Nanjing University Xuanwu District Nanjing Jiangsu Province China

Funding

National Natural Science Foundation of China · Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica

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