ACS Applied Materials & Interfaces
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2024
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IF 8.3
Lujie Zong,Qing Wang,Houyi Sun,Qian Wu,Yaozeng Xu,Huilin Yang,Shujun Lv,Liang Zhang,Dechun Geng
Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration. Unfortunately, currently available clinical drugs are mainly analgesics and cannot alleviate the development of OA. Kartogenin (KGN) has been found to promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes for the treatment of cartilage damage in early OA. However, KGN, as a small hydrophobic molecule, is rapidly cleared from the synovial fluid after intra-articular injection. This study synthesized a KGN-loaded nanocarrier based on PLGA/polydopamine core/shell structure to treat OA. The fluorescence signal of KGN@PLGA/PDA-PEG-E7 nanoparticles lasted for 4 weeks, ensuring long-term sustained release of KGN from a single intra-articular injection. In addition, the polyphenolic structure of PDA enables it to effectively scavenge reactive oxygen species, and the BMSC-targeting peptide E7 (EPLQLKM) endows KGN@PLGA/PDA-PEG-E7 NPs with an effective affinity for BMSCs. As a result, the KGN@PLGA/PDA-PEG-E7 nanoparticles could effectively induce cartilage in vitro and protect the cartilage and subchondral bone in a rat ACLT model. This therapeutic strategy could also be extended to the delivery of other drugs, targeting other tissues to treat joint diseases.
研究领域:
生物医学工程
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药剂学
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骨科
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2016
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IF 3.42
Qian Li,Dongming Xing,Lie Ma,Changyou Gao
As the most promising stem cell, bone marrow-derived mesenchymal stem cells (BMSCs) has attracted many attentions and applied widely in regenerative medicine. A biodegradable polyester with tunable affinity to BMSCs plays critical role in determining the properties of the BMSCs-based constructs. In this study, maleimide functionalized biodegradable polyester (P(MTMC-LA)) was synthesized through ring-opening copolymerization between l -lactide (LA) and furan-maleimide functionalized trimethylene carbonate (FMTMC) and a subsequent retro Diels-Alder reaction. P(MTMC-LA) was modified by different amounts of BMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry to investigate the effect on BMSCs. The E7 peptide modified P(MTMC-LA) was casted into films on glass slides and BMSCs were seeded onto the films. In vitro study showed that E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation compared to unmodified P(MTMC-LA) film. Besides, the adhesion and proliferation were enhanced by the increasing peptide grafting ratio. These results indicated that the novel biodegradable polyester can serve as a biomaterial with great potential application in tissue engineering and regenerative medicine.
研究领域:
生物材料学
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再生医学
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组织工程
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DOI
PubMed
高影响因子
BMC BIOTECHNOLOGY
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2025
·Vol. 25
·期 1
·1-20
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IF 3.4
Long Shengyu,Wang Wentong,Chen Yongcheng,Wang Zhihua,Duan Hao,Yuan Ping,Xu Yunrong,Li Denghui,Zhang Wan,Wang Weizhou,He Fei
Background The repair of bone defects remains a significant clinical challenge. Although magnesium (Mg)-based biomimetic scaffolds are widely utilized for bone defect repair, the release of Mg²⁺ ions often leads to an alkaline microenvironment, thereby adversely affecting bone regeneration. Regenerative medicine strategies that leverage the recruitment of endogenous bone marrow mesenchymal stem cells (BMSCs) offer a novel approach to treating bone defects.Methods In this study, we employed poly(L-lactic acid) (PLLA) and polyethylene glycol (PEG) as shell materials and nanomagnesium oxide (nMgO) combined with gelatin (G) as core materials to fabricate coaxial fibre membranes with a “core‒shell” structure via coaxial electrospinning technology. Additionally, we grafted the BMSC-affinitive peptide E7 (EPLQLKM) onto the fibres to achieve specific recruitment of endogenous BMSCs.Results Morphological and structural analyses confirmed the successful formation of the “core‒shell” structure of the fibre membranes. Grafting E7 peptides enhanced the hydrophilicity and mechanical properties of the fibre membranes and maintained pH stability in vitro. In vitro experiments demonstrated that the functionalized fibre membranes significantly promoted BMSC proliferation, migration, and osteogenic differentiation. When implanted into a rat cranial defect model, we observed the formation of new bone tissue and the repair of the bone defect.Conclusion sE7 peptide-functionalized coaxial fibre membranes effectively facilitated bone defect repair by promoting the recruitment and osteogenic differentiation of BMSCs, demonstrating substantial potential for tissue engineering applications.
研究领域:
生物医学工程
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组织工程
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干细胞生物学
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材料科学与医学应用
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骨科再生医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Wu Shuo,Wang Zongliang,Wang Yu,Guo Min,Zhou Mengyang,Wang Liqiang,Ma Jie,Zhang Peibiao
Mesenchymal stem cells (MSCs) have considerable value in regenerative medicine because of their unique properties such as pluripotency, self-renewal ability, and low immunogenicity. Isolation and purification are prerequisites for various biomedical applications of MSCs, and traditional sorting methods are often expensive, complicated, and difficult to apply on a large scale. In addition to purification, the requirement for expansion of cells also limits the further application of MSCs. The purpose of this study was to develop a unique magnetic sorting microsphere to obtain relatively pure and high-yield MSCs in an economical and effective way, that can also be used for the expansion of MSCs. Poly (ethylene glycol) (PEG)-based anti-adhesive treatment of the prepared oleic acid grafted Fe3O4-poly (lactic-co-glycolic acid) magnetic microspheres was performed, and then E7 peptide was covalently grafted onto the treated microspheres. Upon a series of characterization, the magnetic microspheres were of uniform size, and cells were unable to adhere to the PEG-treated surface. E7 grafting significantly improved cell adhesion and proliferation. The results obtained from separate culture of various cell types as well as static or dynamic co-culture showed that selective adhesion of MSCs was observed on the magnetic sorting microspheres. Furthermore, the cells expanded on the microspheres maintained their phenotype and typical differentiation potentials. The magnetic properties of the microspheres enabled sampling, distribution, and transfer of cells without the usage of trypsin digestion. And it facilitated the separation of cells and microspheres for harvesting of MSCs after digestion. These findings have promising prospects for MSC research and clinical applications.
研究领域:
再生医学
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干细胞生物学
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生物医学工程
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
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2025
·Vol. 16
·期 1
·1-16
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IF 7.3
Chen Guangzi,Xu Tao,Gao Ran,Liu Wenbin,Li Weigang,Zeng Delu,Li Jian,Fang Xuan,Sheng Gaohong,Zhao Hongqi,Liu Chaoxu
Background Periosteum plays an important role in bone defect repair due to its rich vascular network and cells. However, natural periosteum is difficult to meet clinical requirements due to its low availability. Therefore, it is necessary to develop a tissue engineering strategy of biomimetic periosteum for bone defect repair. Methods Poly-ε-caprolactone/chitosan/Whitlockite electrospun bionic membrane (PCL/CS/WH) was prepared using electrospinning technology, then it was conjugated with an E7 peptide as PCL/CS/WH/E7 bionic membrane. The physical properties of the membranes were evaluated by TEM, FTIR and tensile strength testing. In vitro, LIVE/DEAD staining and Cell Counting Kit-8 assay of bone marrow mesenchymal stem cells (BMSCs) and Endothelial progenitor cells (EPCs) are used to assess the biocompatibility of bionic membranes. Matrigel was applied to evaluate the ability of the different composite nanofibers samples to promote angiogenesis. Mineralized nodule and collagen formation in the BMSCs was detected by alizarin red staining and sirius red staining respectively. The expression of osteogenesis related genes and angiogenesis associated genes were detected using quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, the ability of PCL/CS/WH/E7 membrane to promote bone regeneration and angiogenesis was assessed by Micro-CT and associated staining. Result The addition of chitosan (CS) and E7 peptide (E7) enhanced the hydrophilicity and cytocompatibility of pure PCL membranes. Additionally, CS, E7 and Mg 2+ released from Whitlockite (WH) had a synergistic effect to promote angiogenesis and osteogenic differentiation. Three weeks after implantation, the membrane successfully bridged the bone defect and significantly promoted the formation of new bone and blood vessels. Conclusion The PCL/CS/WH/E7 membrane to achieve efficient repair of bone tissue and enriches clinical solutions for the treatment of critical bone defects.
研究领域:
组织工程
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生物材料科学
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再生医学
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骨科
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2020
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IF 8.724
Wei Zhang,Chen Ling,Aini Zhang,Haoyang Liu,Yujie Jiang,Xiaolong Li,Renwang Sheng,Qingqiang Yao,Jialin Chen
Endogenous repair of osteochondral defect is usually limited by the insufficient number of cells in the early stage and incomplete cell differentiation in the later stage. The development of drug delivery systems for sequential release of pro-migratory and pro-chondrogenic molecules to induce endogenous bone marrow-derived mesenchymal stem cells (BMSCs) recruitment and chondrogenic differentiation is highly desirable for in situ osteochondral regeneration. In this study, a novel, all-silk-derived sequential delivery system was fabricated by incorporating the tunable drug-loaded silk fibroin (SF) nanospheres into a SF porous matrix. The loading efficiency and release kinetics of biomolecules depended on the initial SF/polyvinyl alcohol (PVA) concentrations (0.2%, 1% and 5%) of the nanospheres, as well as the hydrophobicity of the loaded molecules, resulting in controllable and programmed delivery profiles. Our findings indicated that the 5% nanosphere-incorporated matrix showed a rapid release of E7 peptide during the first 120 h, whereas the 0.2% nanosphere-incorporated matrix provided a slow and sustained release of Kartogenin (KGN) longer than 30 days. During in vitro culture of BMSCs, this functional SF matrix incorporated with E7/KGN nanospheres showed good biocompatibility, as well as enhanced BMSCs migration and chondrogenic differentiation through the release of E7 and KGN . Furthermore, when implanted into rabbit osteochondral defect, the SF nanosphere matrix with sequential E7/KGN release promoted the regeneration of both cartilage and subchondral bone. This work not only provided a novel all-silk-derived drug delivery system for sequential release of molecules, but also a functional tissue-engineered scaffold for osteochondral regeneration.
研究领域:
生物材料
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组织工程
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药物递送系统
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yuanming Xiao,Yangyang Qu,Xuankai Hu,Jinmin Zhao,Sheng Xu,Li Zheng,Xiaonan Liang
Effective membranes that have the osteogneic potential and the ability to recruit osteoblast precursor cells challenged guided bone regeneration (GBR). Herein, we engineered multifunctional nanofiber membranes by using eletrospun poly(ε-caprolactone) (PCL) and silk fibroin (SF), incorporated with octacalcium phosphate (OCP) and BMSCs-affine peptide (E7) to form the PCL/SF/OCP/E7 (PSOE) nanofiber, wherein the E7 peptide enhances the enrichment of BMSCs, and OCP as osteogenesis promoter. The composite membranes enhance the recruitment and biomineralization processes essential for bone regeneration. Notably, the dual functionality of BMSC recruitment and osteoinduction provides a “recruitment-osteoinduction” strategy that significantly improves bone repair. In vitro analyses confirmed that the PSOE nanofibers have superior hydrophilicity and biocompatibility, and significantly upregulated the expression of osteogenic genes in mesenchymal stem cells, thereby facilitating osteogenic differentiation. In vivo studies using a rat tibial defect model revealed that PSOE nanofibers promoted bone repair within 8 weeks, as validated by micro-CT and histological evaluations. This study highlights the PSOE nanofiber's potential as a promising synthetic periosteum substitute for effective bone regeneration.
研究领域:
生物材料
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组织工程
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再生医学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Qihong Li,Chen Li,Jun Yan,Chunli Zhang,Yu Jiang,Xiantong Hu,Liwei Han,Li Li,Peng Wang,Lingzhou Zhao,Yantao Zhao
Repairing large bone defects remains a significant clinical challenge. Stem cell is of great importance in bone regeneration, and periosteum is rich in periosteal stem cell, which has a great influence on repairing bone defects. Bioengineered periosteum with excellent biocompatibility and stem cell homing capabilities to promote bone regeneration is of great clinical significance. The E7 peptide (EPLQLKM), which exhibits a specific affinity for mesenchymal stem cells (MSCs), is beneficial for modulating cellular functions. In this study, a unique microporous structured carboxymethyl chitosan/sodium alginate membrane with a proper mass ratio is developed by the addition of Poloxam 407 （P407）, which is then functionalized with the E7 affinitive peptide. This membrane, characterized by its microporous structure and E7 peptide functionalization (CSSA/P/E), not only demonstrated favorable mechanical properties, enhanced hydrophilicity, satisfactory biodegradation profile, and excellent biocompatibility, but also synergistically enhanced MSCs recruitment. It is found to promote the proliferation, spreading, and osteogenic differentiation of MSCs in vitro and to accelerate early periosteal regeneration, bone matrix deposition, and vascularization in vivo, leading to effective regeneration of critical-sized bone defects. Overall, this study presents a robust, cell and growth factor-free strategy for bioengineering periosteum, offering a potential solution for the challenging large size bone defects.
研究领域:
组织工程
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生物材料
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再生医学
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干细胞生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2022
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IF 10.761
Wentao Zhang,Tianze Sun,Jing Zhang,Xiantong Hu,Ming Yang,Liwei Han,Gang Xu,Yantao Zhao,Zhonghai Li
The presence of periosteum can greatly affect the repair of a bone fracture. An artificial periosteum imitates the biological function of natural periosteum, which is capable of protecting and maintaining bone tissue structure and promoting bone repair. In our artificial periosteum, biocompatible methacrylate gelatin was used to provide the mechanical support of the membrane, E7 peptide added bioactivity, and Wharton's jelly provided the biological activity support of the membrane, resulting in a hydrogel membrane (G-E-W) for the chemotactic recruitment of bone marrow mesenchymal stem cells (BMSCs) and promoting cell proliferation and osteogenic differentiation. In an in vitro experiment, the G-E-W membrane recruited BMSCs and promoted cell proliferation and osteogenic differentiation. After 4 weeks and 8 weeks of implantation in a rat skull defect, the group implanted with a G-E-W membrane was superior to the blank control group and single-component membrane group in both quantity and quality of new bone. The artificial G-E-W membrane recruits BMSC chemotaxis and promotes cell proliferation and osteogenic differentiation, thereby effectively improving the repair efficiency of fractures and bone defects.
研究领域:
组织工程
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生物材料
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干细胞生物学
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再生医学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Yize Zhao,Xing Li,Chengkun Zhao,Yujiang Fan,Ganjun Feng,Yong Sun
Endogenous regeneration of the nucleus pulposus (NP) is hindered by inefficient recruitment of stem/progenitor cells, limited control over differentiation, and poor matrix maintenance. Here, we developed a microsphere-based platform (GBKE) that transforms upon mild hydration into a dynamic, self-healing hydrogel, allowing in situ gelation and stable retention within soft tissues. The hydrogel forms a highly porous, interconnected network that facilitates nutrient transport and deep cellular infiltration. The microspheres form an interpenetrating network structure by co-assembling through β-sheet/π-π stacking driven self-assembly, combining gelatin methacrylamide (GelMA) with the self-assembling small molecule BPAA-GFF. The chondrogenic-inducing small molecule kartogenin is bound to the BPAA-GFF nanofiber network through non-covalent interactions such as hydrogen bonds and hydrophobic forces, achieving sustained inducing effect. The MSC affinity peptide E7 is covalently coupled to the surface of the microspheres to achieve targeted cell homing. Thanks to the enhanced effect of the nanofiber network induced by BPAA-GFF, the storage modulus (≈1700 Pa) and critical shear stress (≈35 Pa) of the microgels are significantly higher than those of pure GelMA microgel. In vivo, GBKE microgels significantly improved disc height index and extracellular matrix restoration in rat models, maintaining NP regeneration for at least 8 weeks. In rabbit models, MRI analyses and histological results confirmed durable structural and functional repair for up to 12 weeks. This system enables the programmed regulation of endogenous cell behavior, offering a promising approach for minimally invasive intervertebral disc repair.
研究领域:
生物医学工程
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组织工程
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再生医学
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生物材料
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骨科
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 6
·1240-1261
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IF 7
Po Zhang,Jialin Chen,Yuzhi Sun,Zhicheng Cao,Yanan Zhang,Qingyun Mo,Qingqiang Yao,Wei Zhang
Osteochondral defect (OCD) regeneration remains a great challenge. Recently, multilayer scaffold simulating native osteochondral structures have aroused broad interest in osteochondral tissue engineering. Here, we developed a 3D multifunctional bi-layer scaffold composed of a kartogenin (KGN)-loaded GelMA hydrogel (GelMA/KGN) as an upper layer mimicking a cartilage-specific extracellular matrix and a hydroxyapatite (HA)-coated 3D printed polycaprolactone porous scaffold (PCL/HA) as a lower layer simulating subchondral bone. The bi-layer scaffolds were subsequently modified with tannic acid (TA) prime-coating and E7 peptide conjugation (PCL/HA-GelMA/KGN@TA/E7) to regulate endogenous stem cell behaviors and exert antioxidant activity for enhanced osteochondral regeneration. In vitro, the scaffolds could support cell attachment and proliferation, and enhance the chondrogenic and osteogenic differentiation capacity of bone marrow-derived mesenchymal stem cells (BMSCs) in a specific layer. Besides, the incorporation of TA/E7 significantly increased the biological activity of the bi-layer scaffolds including the pro-migratory effect, antioxidant activity, and the maintenance of cell viability against oxidative stress. In vivo, the developed bi-layer scaffolds enhanced the simultaneous regeneration of cartilage and subchondral bone when implanted into a rabbit OCD model through macroscopic, micro-CT, and histological evaluation. Taken together, these investigations demonstrated that the 3D multifunctional bi-layer scaffolds could provide a suitable microenvironment for endogenous stem cells, and promote in situ osteochondral regeneration, showing great potential for the clinical treatment of OCD.
研究领域:
组织工程
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再生医学
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生物材料
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干细胞生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
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IF 9.4
Xiaoyu Zhang,Lang Bai,Jing Zhou,Hua Gao,Qi Chen,Wenguo Cui,Xing Yang,Yuefeng Hao
An effective treatment for the irregular partial-thickness cartilage defect in the early stages of osteoarthritis (OA) is lacking. Cartilage tissue engineering is effective for treating full-thickness cartilage defects with limited area. In this study, we designed an injectable multifunctional poly(lactic-co-glycolic acid) (PLGA) microsphere to repair partial-thickness cartilage defects. The microsphere was grafted with an E7 peptide after loading the microsphere with kartogenin (KGN) and modifying the outer layer through dopamine self-polymerization. The microsphere could adhere to the cartilage defect, recruit synovial mesenchymal stem cells (SMSCs) in situ, and stimulate their differentiation into chondrocytes after injection into the articular cavity. Through in vivo and in vitro experiments, we demonstrated the ability of multifunctional microspheres to adhere to cartilage matrix, recruit SMSCs, and promote their differentiation into cartilage. Following treatment, the cartilage surface of the model group with partial-thickness cartilage defect showed smooth recovery, and the glycosaminoglycan content remained normal; the untreated control group showed significant progression of OA. The microsphere, a framework for cartilage tissue engineering, promoted the expression of SMSCs involved in cartilage repair while adapting to cell migration and growth. Thus, for treating partial-thickness cartilage defects in OA, this innovative carrier system based on stem cell therapy can potentially improve therapeutic outcomes. Statement of significance Mesenchymal stem cells (MSCs) therapy is effective in the repair of cartilage injury. However, because of the particularity of partial-thickness cartilage injury, it is difficult to recruit enough seed cells in situ, and there is a lack of suitable scaffolds for cell migration and growth. Here, we developed polydopamine surface-modified PLGA microspheres (PMS) containing KGN and E7 peptides. The adhesion ability of the microspheres is facilitated by the polydopamine layer wrapped in them; thus, the microspheres can adhere to the injured cartilage and recruit MSCs, thereby promoting their differentiation into chondrocytes and accomplishing cartilage repair. The multifunctional microspheres can be used as a safe and potential method to treat partial-thickness cartilage defects in OA.
研究领域:
生物医学工程
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组织工程
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干细胞疗法
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骨科
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）