Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice
Poor tendon–bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic...
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13638 |
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| author | Jianting Li Guanfu Wu Changhao Xu Zhining Cai Jiali Ji Ziyi Yu Jing Zhang Jiali Wang |
| author_facet | Jianting Li Guanfu Wu Changhao Xu Zhining Cai Jiali Ji Ziyi Yu Jing Zhang Jiali Wang |
| author_sort | Jianting Li |
| collection | DOAJ |
| description | Poor tendon–bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon–bone integration, which may be ascribed to modulation of angiogenesis–osteogenesis crosstalk coupled by type H vessels. |
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| language | English |
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| publishDate | 2023-09-01 |
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| spelling | doaj.art-f461301139ed4478933d01a235e1ab0c2023-11-19T08:20:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124171363810.3390/ijms241713638Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in MiceJianting Li0Guanfu Wu1Changhao Xu2Zhining Cai3Jiali Ji4Ziyi Yu5Jing Zhang6Jiali Wang7School of Biomedical Engineering, Sun Yat-sen University Shenzhen Campus, Shenzhen 518107, ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, 30 Puzhu South Road, Nanjing 211816, ChinaSchool of Biomedical Engineering, Sun Yat-sen University Shenzhen Campus, Shenzhen 518107, ChinaSchool of Biomedical Engineering, Sun Yat-sen University Shenzhen Campus, Shenzhen 518107, ChinaSchool of Biomedical Engineering, Sun Yat-sen University Shenzhen Campus, Shenzhen 518107, ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, 30 Puzhu South Road, Nanjing 211816, ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, 30 Puzhu South Road, Nanjing 211816, ChinaSchool of Biomedical Engineering, Sun Yat-sen University Shenzhen Campus, Shenzhen 518107, ChinaPoor tendon–bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon–bone integration, which may be ascribed to modulation of angiogenesis–osteogenesis crosstalk coupled by type H vessels.https://www.mdpi.com/1422-0067/24/17/13638type H vesselstendon–bone healingslit3HMP |
| spellingShingle | Jianting Li Guanfu Wu Changhao Xu Zhining Cai Jiali Ji Ziyi Yu Jing Zhang Jiali Wang Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice International Journal of Molecular Sciences type H vessels tendon–bone healing slit3 HMP |
| title | Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice |
| title_full | Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice |
| title_fullStr | Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice |
| title_full_unstemmed | Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice |
| title_short | Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice |
| title_sort | slit guidance ligand 3 slit3 loaded in hydrogel microparticles enhances the tendon bone healing through promotion of type h vessel formation an experimental study in mice |
| topic | type H vessels tendon–bone healing slit3 HMP |
| url | https://www.mdpi.com/1422-0067/24/17/13638 |
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