Development and mechanistic investigation of recombinant type III humanized collagen gel for mid-facial soft tissue repair
Abstract Mid-facial depression is a key sign of facial aging, primarily caused by the loss of collagen leading to depletion of the extracellular matrix (ECM). However, the existing fillers for soft tissue augmentation have shown certain limitations in repairing mid-facial depression. Therefore, we h...
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| Language: | English |
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SpringerOpen
2025-06-01
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| Series: | Collagen and Leather |
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| Online Access: | https://doi.org/10.1186/s42825-025-00196-8 |
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| author | Qian Wang Qifei An Yuanzhou Wang Jingbo Yang Xiujuan Zhang Shibo Jiang Min Chen Lu Lu Yun Zhu |
| author_facet | Qian Wang Qifei An Yuanzhou Wang Jingbo Yang Xiujuan Zhang Shibo Jiang Min Chen Lu Lu Yun Zhu |
| author_sort | Qian Wang |
| collection | DOAJ |
| description | Abstract Mid-facial depression is a key sign of facial aging, primarily caused by the loss of collagen leading to depletion of the extracellular matrix (ECM). However, the existing fillers for soft tissue augmentation have shown certain limitations in repairing mid-facial depression. Therefore, we herein report the development of a novel recombinant humanized type III collagen gel (C3Gel) through rational design and modification of a commercially available recombinant type III humanized collagen lyophilized fiber product. Both biological activity and tissue repair mechanisms of C3Gel were systematically evaluated in vitro and in vivo. C3Gel formed a dense fibrous structure around cells, significantly improving the ECM environment and providing strong support for cells, thereby promoting cell adhesion, migration, and proliferation. After injection of C3Gel into the dorsal region of rats, we observed a significant increase in the expression of type I collagen and elastin that improved tissue mechanical properties and elasticity. High-throughput RNA sequencing analysis revealed that C3Gel activated the integrin signaling pathway to improve binding between cells and ECM, resulting in the increased expression of downstream genes by activating the PI3K-Akt pathway which promoted the production of ECM components, such as collagen and laminin. At the same time, the expression of matrix metalloproteinases was inhibited to maintain ECM stability. Moreover, C3Gel is not carcinogenic in mice. Therefore, C3Gel demonstrates excellent biocompatibility and significant tissue repair ability, offering a safe, efficient, and long-term stable solution for mid-facial soft tissue augmentation, while providing new insights for other applications in regenerative medicine. Graphical abstract |
| format | Article |
| id | doaj-art-36928429d33a46d1b1ca2138aed3cea6 |
| institution | DOAJ |
| issn | 2097-1419 2731-6998 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Collagen and Leather |
| spelling | doaj-art-36928429d33a46d1b1ca2138aed3cea62025-08-20T03:16:41ZengSpringerOpenCollagen and Leather2097-14192731-69982025-06-017111610.1186/s42825-025-00196-8Development and mechanistic investigation of recombinant type III humanized collagen gel for mid-facial soft tissue repairQian Wang0Qifei An1Yuanzhou Wang2Jingbo Yang3Xiujuan Zhang4Shibo Jiang5Min Chen6Lu Lu7Yun Zhu8Key Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/Chinese Academy of Medical Science), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan UniversityShanxi Key Laboratory of Functional Proteins, School of Basic Medicine Sciences, Shanxi Medical UniversityKey Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/Chinese Academy of Medical Science), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan UniversityImperial College LondonCenter for Translational Medicine, Thomas Jefferson UniversityKey Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/Chinese Academy of Medical Science), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan UniversityShanxi Key Laboratory of Functional Proteins, School of Basic Medicine Sciences, Shanxi Medical UniversityKey Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/Chinese Academy of Medical Science), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan UniversityKey Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesAbstract Mid-facial depression is a key sign of facial aging, primarily caused by the loss of collagen leading to depletion of the extracellular matrix (ECM). However, the existing fillers for soft tissue augmentation have shown certain limitations in repairing mid-facial depression. Therefore, we herein report the development of a novel recombinant humanized type III collagen gel (C3Gel) through rational design and modification of a commercially available recombinant type III humanized collagen lyophilized fiber product. Both biological activity and tissue repair mechanisms of C3Gel were systematically evaluated in vitro and in vivo. C3Gel formed a dense fibrous structure around cells, significantly improving the ECM environment and providing strong support for cells, thereby promoting cell adhesion, migration, and proliferation. After injection of C3Gel into the dorsal region of rats, we observed a significant increase in the expression of type I collagen and elastin that improved tissue mechanical properties and elasticity. High-throughput RNA sequencing analysis revealed that C3Gel activated the integrin signaling pathway to improve binding between cells and ECM, resulting in the increased expression of downstream genes by activating the PI3K-Akt pathway which promoted the production of ECM components, such as collagen and laminin. At the same time, the expression of matrix metalloproteinases was inhibited to maintain ECM stability. Moreover, C3Gel is not carcinogenic in mice. Therefore, C3Gel demonstrates excellent biocompatibility and significant tissue repair ability, offering a safe, efficient, and long-term stable solution for mid-facial soft tissue augmentation, while providing new insights for other applications in regenerative medicine. Graphical abstracthttps://doi.org/10.1186/s42825-025-00196-8Recombinant type III humanized collagenGelFunctionMechanism of actionStabilization |
| spellingShingle | Qian Wang Qifei An Yuanzhou Wang Jingbo Yang Xiujuan Zhang Shibo Jiang Min Chen Lu Lu Yun Zhu Development and mechanistic investigation of recombinant type III humanized collagen gel for mid-facial soft tissue repair Collagen and Leather Recombinant type III humanized collagen Gel Function Mechanism of action Stabilization |
| title | Development and mechanistic investigation of recombinant type III humanized collagen gel for mid-facial soft tissue repair |
| title_full | Development and mechanistic investigation of recombinant type III humanized collagen gel for mid-facial soft tissue repair |
| title_fullStr | Development and mechanistic investigation of recombinant type III humanized collagen gel for mid-facial soft tissue repair |
| title_full_unstemmed | Development and mechanistic investigation of recombinant type III humanized collagen gel for mid-facial soft tissue repair |
| title_short | Development and mechanistic investigation of recombinant type III humanized collagen gel for mid-facial soft tissue repair |
| title_sort | development and mechanistic investigation of recombinant type iii humanized collagen gel for mid facial soft tissue repair |
| topic | Recombinant type III humanized collagen Gel Function Mechanism of action Stabilization |
| url | https://doi.org/10.1186/s42825-025-00196-8 |
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