Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo Study
Osteoarthritis is a prevalent musculoskeletal disorder in the elderly, which leads to high rates of morbidity. Mesenchymal stem cells (MSCs) are a promising approach to promote tissue regeneration in the absence of effective long-term treatments. Small molecules are relatively inexpensive and can se...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Bioengineering |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2306-5354/10/7/847 |
| _version_ | 1797590217496985600 |
|---|---|
| author | Chih-Hsiang Fang Yi-Wen Lin Chung-Kai Sun Jui-Sheng Sun |
| author_facet | Chih-Hsiang Fang Yi-Wen Lin Chung-Kai Sun Jui-Sheng Sun |
| author_sort | Chih-Hsiang Fang |
| collection | DOAJ |
| description | Osteoarthritis is a prevalent musculoskeletal disorder in the elderly, which leads to high rates of morbidity. Mesenchymal stem cells (MSCs) are a promising approach to promote tissue regeneration in the absence of effective long-term treatments. Small molecules are relatively inexpensive and can selectively alter stem cell behavior during their differentiation, making them an attractive option for clinical applications. In this study, we developed an extracellular matrix (ECM)-based biphasic scaffold (BPS) loaded with two small-molecule drugs, kartogenin (KGN) and metformin (MET). This cell-free biomimetic biphasic scaffold consists of a bone (gelatin/hydroxyapatite scaffold embedded with metformin [GHSM]) and cartilage (nano-gelatin fiber embedded with kartogenin [NGFK]) layer designed to stimulate osteochondral regeneration. Extracellular matrix (ECM)-based biomimetic scaffolds can promote native cell recruitment, infiltration, and differentiation even in the absence of additional growth factors. The biphasic scaffold (BPS) showed excellent biocompatibility in vitro, with mesenchymal stem cells (MSCs) adhering, proliferating, and differentiated on the biomimetic biphasic scaffolds (GHSM and NGFK layers). The biphasic scaffolds upregulated both osteogenic and chondrogenic gene expression, sulfated glycosaminoglycan (sGAG), osteo- and chondrogenic biomarker, and relative mRNA gene expression. In an in vivo rat model, histo-morphological staining showed effective regeneration of osteochondral defects. This novel BPS has the potential to enhance both subchondral bone repair and cartilage regeneration, demonstrating excellent effects on cell homing and the recruitment of endogenous stem cells. |
| first_indexed | 2024-03-11T01:17:25Z |
| format | Article |
| id | doaj.art-3ddcbc5f038c43efa3d18dc08b5c799d |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-11T01:17:25Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-3ddcbc5f038c43efa3d18dc08b5c799d2023-11-18T18:22:11ZengMDPI AGBioengineering2306-53542023-07-0110784710.3390/bioengineering10070847Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo StudyChih-Hsiang Fang0Yi-Wen Lin1Chung-Kai Sun2Jui-Sheng Sun3Trauma and Emergency Center, China Medical University Hospital, No. 2, Xueshi Road, North Dist., Taichung City 40447, TaiwanInstitute of Biomedical Engineering, College of Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, TaiwanInstitute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei 11221, TaiwanDepartment of Orthopedic Surgery, En Chu Kong Hospital, No. 399, Fuxing Road, New Taipei City 23741, TaiwanOsteoarthritis is a prevalent musculoskeletal disorder in the elderly, which leads to high rates of morbidity. Mesenchymal stem cells (MSCs) are a promising approach to promote tissue regeneration in the absence of effective long-term treatments. Small molecules are relatively inexpensive and can selectively alter stem cell behavior during their differentiation, making them an attractive option for clinical applications. In this study, we developed an extracellular matrix (ECM)-based biphasic scaffold (BPS) loaded with two small-molecule drugs, kartogenin (KGN) and metformin (MET). This cell-free biomimetic biphasic scaffold consists of a bone (gelatin/hydroxyapatite scaffold embedded with metformin [GHSM]) and cartilage (nano-gelatin fiber embedded with kartogenin [NGFK]) layer designed to stimulate osteochondral regeneration. Extracellular matrix (ECM)-based biomimetic scaffolds can promote native cell recruitment, infiltration, and differentiation even in the absence of additional growth factors. The biphasic scaffold (BPS) showed excellent biocompatibility in vitro, with mesenchymal stem cells (MSCs) adhering, proliferating, and differentiated on the biomimetic biphasic scaffolds (GHSM and NGFK layers). The biphasic scaffolds upregulated both osteogenic and chondrogenic gene expression, sulfated glycosaminoglycan (sGAG), osteo- and chondrogenic biomarker, and relative mRNA gene expression. In an in vivo rat model, histo-morphological staining showed effective regeneration of osteochondral defects. This novel BPS has the potential to enhance both subchondral bone repair and cartilage regeneration, demonstrating excellent effects on cell homing and the recruitment of endogenous stem cells.https://www.mdpi.com/2306-5354/10/7/847metforminkartogenincartilagebonetissue engineering |
| spellingShingle | Chih-Hsiang Fang Yi-Wen Lin Chung-Kai Sun Jui-Sheng Sun Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo Study Bioengineering metformin kartogenin cartilage bone tissue engineering |
| title | Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo Study |
| title_full | Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo Study |
| title_fullStr | Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo Study |
| title_full_unstemmed | Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo Study |
| title_short | Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo Study |
| title_sort | small molecule loaded biomimetic biphasic scaffold for osteochondral regeneration an in vitro and in vivo study |
| topic | metformin kartogenin cartilage bone tissue engineering |
| url | https://www.mdpi.com/2306-5354/10/7/847 |
| work_keys_str_mv | AT chihhsiangfang smallmoleculeloadedbiomimeticbiphasicscaffoldforosteochondralregenerationaninvitroandinvivostudy AT yiwenlin smallmoleculeloadedbiomimeticbiphasicscaffoldforosteochondralregenerationaninvitroandinvivostudy AT chungkaisun smallmoleculeloadedbiomimeticbiphasicscaffoldforosteochondralregenerationaninvitroandinvivostudy AT juishengsun smallmoleculeloadedbiomimeticbiphasicscaffoldforosteochondralregenerationaninvitroandinvivostudy |