Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair
The regeneration of critical-sized osteochondral defects remains a significant challenge due to the limited self-healing capacity of cartilage. Traditional approaches, such as autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI), have shown promise...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-01-01
|
| Series: | Engineered Regeneration |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666138125000052 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849739581080993792 |
|---|---|
| author | Gang Zhong Yixuan Luo Meng Wang Zhengran Yu Xuenong Zou Gang Wang Fei Chen Yin Yu |
| author_facet | Gang Zhong Yixuan Luo Meng Wang Zhengran Yu Xuenong Zou Gang Wang Fei Chen Yin Yu |
| author_sort | Gang Zhong |
| collection | DOAJ |
| description | The regeneration of critical-sized osteochondral defects remains a significant challenge due to the limited self-healing capacity of cartilage. Traditional approaches, such as autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI), have shown promise but are limited by issues like insufficient cell availability, dedifferentiation of chondrocytes during expansion, and the formation of fibrocartilage rather than functional hyaline cartilage. This study presents a promising approach utilizing transcript-activated matrices (TAMs) with mRNA to enhance the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) in situ. Chemically modified mRNA (cmRNA) encoding transforming growth factor β3 (TGF-β3) was encapsulated in a collagen hydrogel to provide localized, sustained delivery of chondrogenic signals. In a rat model of critical-sized osteochondral defects, this strategy significantly promoted cartilage regeneration, achieving structural and molecular restoration within six weeks. Histological and biochemical analyses revealed robust chondrogenesis, enhanced extracellular matrix deposition, and superior mechanical properties. Moreover, TAM therapy maintained subchondral bone integrity This work highlights the transformative potential of mRNA-activated matrices as a platform technology that not only addresses key limitations of existing cartilage repair strategies but also provides a biomimetic microenvironment that guides stem cell differentiation and tissue regeneration. |
| format | Article |
| id | doaj-art-e346b8caacef4bfbbf2860557adcc1a2 |
| institution | DOAJ |
| issn | 2666-1381 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Engineered Regeneration |
| spelling | doaj-art-e346b8caacef4bfbbf2860557adcc1a22025-08-20T03:06:14ZengKeAi Communications Co., Ltd.Engineered Regeneration2666-13812025-01-01611112010.1016/j.engreg.2025.03.002Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repairGang Zhong0Yixuan Luo1Meng Wang2Zhengran Yu3Xuenong Zou4Gang Wang5Fei Chen6Yin Yu7Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR ChinaCenter for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR ChinaCenter for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR ChinaGuangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, PR ChinaGuangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, PR ChinaSIAT-GeneHeal Medicine mRNA Regenerative Medicine Laboratory, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Corresponding authors at: Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; Corresponding authors at: Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; Corresponding authors at: Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.The regeneration of critical-sized osteochondral defects remains a significant challenge due to the limited self-healing capacity of cartilage. Traditional approaches, such as autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI), have shown promise but are limited by issues like insufficient cell availability, dedifferentiation of chondrocytes during expansion, and the formation of fibrocartilage rather than functional hyaline cartilage. This study presents a promising approach utilizing transcript-activated matrices (TAMs) with mRNA to enhance the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) in situ. Chemically modified mRNA (cmRNA) encoding transforming growth factor β3 (TGF-β3) was encapsulated in a collagen hydrogel to provide localized, sustained delivery of chondrogenic signals. In a rat model of critical-sized osteochondral defects, this strategy significantly promoted cartilage regeneration, achieving structural and molecular restoration within six weeks. Histological and biochemical analyses revealed robust chondrogenesis, enhanced extracellular matrix deposition, and superior mechanical properties. Moreover, TAM therapy maintained subchondral bone integrity This work highlights the transformative potential of mRNA-activated matrices as a platform technology that not only addresses key limitations of existing cartilage repair strategies but also provides a biomimetic microenvironment that guides stem cell differentiation and tissue regeneration.http://www.sciencedirect.com/science/article/pii/S2666138125000052Osteochondral defectsTranscript-activated matrixTGF-β3, Osteoarthritis |
| spellingShingle | Gang Zhong Yixuan Luo Meng Wang Zhengran Yu Xuenong Zou Gang Wang Fei Chen Yin Yu Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair Engineered Regeneration Osteochondral defects Transcript-activated matrix TGF-β3, Osteoarthritis |
| title | Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair |
| title_full | Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair |
| title_fullStr | Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair |
| title_full_unstemmed | Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair |
| title_short | Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair |
| title_sort | transcript activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair |
| topic | Osteochondral defects Transcript-activated matrix TGF-β3, Osteoarthritis |
| url | http://www.sciencedirect.com/science/article/pii/S2666138125000052 |
| work_keys_str_mv | AT gangzhong transcriptactivatedcollagenmatrixforenhancedbonemarrowstemcelldifferentiationandosteochondralrepair AT yixuanluo transcriptactivatedcollagenmatrixforenhancedbonemarrowstemcelldifferentiationandosteochondralrepair AT mengwang transcriptactivatedcollagenmatrixforenhancedbonemarrowstemcelldifferentiationandosteochondralrepair AT zhengranyu transcriptactivatedcollagenmatrixforenhancedbonemarrowstemcelldifferentiationandosteochondralrepair AT xuenongzou transcriptactivatedcollagenmatrixforenhancedbonemarrowstemcelldifferentiationandosteochondralrepair AT gangwang transcriptactivatedcollagenmatrixforenhancedbonemarrowstemcelldifferentiationandosteochondralrepair AT feichen transcriptactivatedcollagenmatrixforenhancedbonemarrowstemcelldifferentiationandosteochondralrepair AT yinyu transcriptactivatedcollagenmatrixforenhancedbonemarrowstemcelldifferentiationandosteochondralrepair |