Self-assembled hybrid hydrogel microspheres create a bone marrow-mimicking niche for bone regeneration
Bone marrow (BM), a natural niche rich in growth factors and bone marrow mesenchymal stem cells (BMSCs), provides an optimal regenerative microenvironment and is widely used in clinical applications. However, the limited proliferative capacity of BMSCs and the mismatch between bone regeneration and...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2025-12-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25003561 |
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| author | Zhi He Peilun Hu Zifan Li Kaige Mao Jingchuan Zheng Chun-Yi Yang Yuyang Luo Jia Yang Zheng Cao Jingsong Lu Xiaobin Luo Sengpav Tong Zhijun He Kunkoo Kim Yaosai Liu Xiaodan Sun Lingyun Zhao Yongwei Pan Yongping Cao Yu Wang Xiumei Wang |
| author_facet | Zhi He Peilun Hu Zifan Li Kaige Mao Jingchuan Zheng Chun-Yi Yang Yuyang Luo Jia Yang Zheng Cao Jingsong Lu Xiaobin Luo Sengpav Tong Zhijun He Kunkoo Kim Yaosai Liu Xiaodan Sun Lingyun Zhao Yongwei Pan Yongping Cao Yu Wang Xiumei Wang |
| author_sort | Zhi He |
| collection | DOAJ |
| description | Bone marrow (BM), a natural niche rich in growth factors and bone marrow mesenchymal stem cells (BMSCs), provides an optimal regenerative microenvironment and is widely used in clinical applications. However, the limited proliferative capacity of BMSCs and the mismatch between bone regeneration and growth factors release constrain their effectiveness in treating critical bone defects. Drawing inspiration from the regenerative properties of BM, we developed self-assembled hybrid microspheres to replicate its function and address these challenges through a tissue engineering approach. This BM-mimicking niche enriched BMSCs via fast-degrading gelatin methacryloyl (GelMA) microspheres, which were loaded with exogenous BMSCs and conjugated with stem cell homing peptides (SKP) to recruit endogenous BMSCs. SKP further enhanced the stemness of BMSCs, thereby promoting angiogenesis and resolving inflammation. Slow-degrading chitosan methacryloyl (ChitoMA) microspheres facilitated sustained release of angiogenic (KLT) and osteogenic (OGP) peptides, supporting blood vessel maturation and osteogenesis. The early release of BMSCs and SKP, followed by the subsequent release of OGP and KLT, aligned with the dynamic process of bone regeneration. In a rat critical femoral condyle defect model, the BM-mimicking niche formed an in-situ ossification center, significantly enhancing bone regeneration. This study introduces a novel BM-mimicking niche characterized by a BMSC-enriched environment and the sequential release of therapeutic factors, offering a promising strategy for treating critical bone defects. |
| format | Article |
| id | doaj-art-db19fa2e8371427384daa09d75720999 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-db19fa2e8371427384daa09d757209992025-08-20T03:44:14ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-12-015417920010.1016/j.bioactmat.2025.08.003Self-assembled hybrid hydrogel microspheres create a bone marrow-mimicking niche for bone regenerationZhi He0Peilun Hu1Zifan Li2Kaige Mao3Jingchuan Zheng4Chun-Yi Yang5Yuyang Luo6Jia Yang7Zheng Cao8Jingsong Lu9Xiaobin Luo10Sengpav Tong11Zhijun He12Kunkoo Kim13Yaosai Liu14Xiaodan Sun15Lingyun Zhao16Yongwei Pan17Yongping Cao18Yu Wang19Xiumei Wang20State Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaInstitute of Orthopedics, Chinese PLA General Hospital, Beijing, 100036, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China; School of Life Science, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, ChinaSpine Section, Peking University First Hospital, Beijing, 100034, ChinaSpine Section, Peking University First Hospital, Beijing, 100034, China; Corresponding author.State Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Corresponding author.Bone marrow (BM), a natural niche rich in growth factors and bone marrow mesenchymal stem cells (BMSCs), provides an optimal regenerative microenvironment and is widely used in clinical applications. However, the limited proliferative capacity of BMSCs and the mismatch between bone regeneration and growth factors release constrain their effectiveness in treating critical bone defects. Drawing inspiration from the regenerative properties of BM, we developed self-assembled hybrid microspheres to replicate its function and address these challenges through a tissue engineering approach. This BM-mimicking niche enriched BMSCs via fast-degrading gelatin methacryloyl (GelMA) microspheres, which were loaded with exogenous BMSCs and conjugated with stem cell homing peptides (SKP) to recruit endogenous BMSCs. SKP further enhanced the stemness of BMSCs, thereby promoting angiogenesis and resolving inflammation. Slow-degrading chitosan methacryloyl (ChitoMA) microspheres facilitated sustained release of angiogenic (KLT) and osteogenic (OGP) peptides, supporting blood vessel maturation and osteogenesis. The early release of BMSCs and SKP, followed by the subsequent release of OGP and KLT, aligned with the dynamic process of bone regeneration. In a rat critical femoral condyle defect model, the BM-mimicking niche formed an in-situ ossification center, significantly enhancing bone regeneration. This study introduces a novel BM-mimicking niche characterized by a BMSC-enriched environment and the sequential release of therapeutic factors, offering a promising strategy for treating critical bone defects.http://www.sciencedirect.com/science/article/pii/S2452199X25003561Bone marrowBone marrow mesenchymal stem cellsHydrogel microspheresBioactive peptidesBone regeneration |
| spellingShingle | Zhi He Peilun Hu Zifan Li Kaige Mao Jingchuan Zheng Chun-Yi Yang Yuyang Luo Jia Yang Zheng Cao Jingsong Lu Xiaobin Luo Sengpav Tong Zhijun He Kunkoo Kim Yaosai Liu Xiaodan Sun Lingyun Zhao Yongwei Pan Yongping Cao Yu Wang Xiumei Wang Self-assembled hybrid hydrogel microspheres create a bone marrow-mimicking niche for bone regeneration Bioactive Materials Bone marrow Bone marrow mesenchymal stem cells Hydrogel microspheres Bioactive peptides Bone regeneration |
| title | Self-assembled hybrid hydrogel microspheres create a bone marrow-mimicking niche for bone regeneration |
| title_full | Self-assembled hybrid hydrogel microspheres create a bone marrow-mimicking niche for bone regeneration |
| title_fullStr | Self-assembled hybrid hydrogel microspheres create a bone marrow-mimicking niche for bone regeneration |
| title_full_unstemmed | Self-assembled hybrid hydrogel microspheres create a bone marrow-mimicking niche for bone regeneration |
| title_short | Self-assembled hybrid hydrogel microspheres create a bone marrow-mimicking niche for bone regeneration |
| title_sort | self assembled hybrid hydrogel microspheres create a bone marrow mimicking niche for bone regeneration |
| topic | Bone marrow Bone marrow mesenchymal stem cells Hydrogel microspheres Bioactive peptides Bone regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25003561 |
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