Nature Communications
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2025
·Vol. 16
·期 1
·1-19
·
IF 15.7
Ding Zichuan,Cai Yongrui,Sun Haocheng,Rong Xiao,Ye Sipei,Fan Jiaxuan,Lai Yahao,Liang Zhimin,Huang Chao,Li Peilin,Fu Xiaoxue,Wang Liu,Tang Guosheng,Zhou Zongke,Luo Zeyu
Regenerating natural gradients of the tendon‒bone interface (TBI) is a major challenge in the reconstruction of rotator cuff tear (RCT). In this study, magnetic Janus hydrogel microrobots to match the TBI orientation during RCT reconstruction surgery are developed via a biofriendly gas-shearing microfluidic platform. Through separate loading of Mg 2+ and Zn 2+ , the microrobots facilitate the immediate restoration and long-term maintenance of the natural mineral gradient in the TBI after implantation and alignment through magnetic manipulation. In vitro studies confirm the spatiotemporal cell phenotype modulation effects of the microrobots. In a rat RCT model, microrobots synchronously promote the bone and tendon regeneration, and the restoration of gradient tendon‒bone transition structures in the TBI. Overall, by rebuilding the Mg 2+ /Zn 2+ mineral gradient, cell phenotype gradient and structural gradient of the TBI, magnetic Janus microrobots loaded with dual bioactive ions represent a promising strategy for promoting TBI healing in RCT reconstruction surgery.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2025
·
IF 4.8
Xiping Jiang,Hui Xu,Xinyue Sun,Xuefan Yang,Yuxuan Xia,Wen Xue,Yaohua He
Introduction: The high rate of retear following rotator cuff repair is largely attributed to the absence of a fibrocartilage layer and limited bone regeneration capacity. We aim to evaluate a bioadhesive derived from decellularized porcine annulus fibrosus extracellular matrix, loaded with zeolitic imidazolate framework-8 (ZIF-8), and to promote rotator cuff tendon–bone healing.Methods: Three adhesive formulations were developed: (1) silk fibroin/tannic acid (ST group), (2) ST combined with decellularized porcine annulus fibrosus extracellular matrix (ST/dECM group), and (3) ST/dECM supplemented with ZIF-8 (ST/dECM/ZIF-8 group). Optimal component ratios were determined using lap shear strength testing. The microstructure, Fourier transform infrared (FTIR) spectra, swelling behavior, and degradation properties of the materials were characterized. In vitro studies assessed the adhesives’ effects on cytotoxicity, proliferation, and the chondrogenic and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs). A rat rotator cuff repair model was used to evaluate in vivo anti-inflammatory effects, fibrocartilage and bone regeneration, and biomechanical performance.Results: All adhesive formulations exhibited comparable tissue adhesion strength and biocompatibility. Both the ST/dECM and ST/dECM/ZIF-8 groups enhanced BMSC chondrogenic differentiation compared to the ST group, with the ST/dECM/ZIF-8 group showing superior osteogenic induction. In vivo, the ST/dECM/ZIF-8 hydrogel effectively reduced interfacial inflammation and promoted fibrocartilage and bone regeneration. Biomechanical testing demonstrated significantly higher ultimate load, tensile stress, and stiffness in all adhesive-treated groups compared to untreated controls.Conclusion: The ST/dECM/ZIF-8 bioadhesive hydrogel promotes fibrocartilage and bone regeneration. These findings highlight its potential as a promising biomaterial-based strategy to enhance tendon-to-bone interface healing following rotator cuff repair.
研究领域:
生物材料
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组织工程
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骨科手术
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再生医学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-17
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IF 10.435
Liao Haoran,Yu Han-Ping,Song Wei,Zhang Guangcheng,Lu Bingqiang,Zhu Ying-Jie,Yu Weilin,He Yaohua
Background Rotator cuff tear (RCT) is a common problem of the musculoskeletal system. With the advantage of promoting bone formation, calcium phosphate materials have been widely used to augment tendon-bone healing. However, only enhancing bone regeneration may be not enough for improving tendon–bone healing. Angiogenesis is another fundamental factor required for tendon–bone healing. Therefore, it’s necessary to develop a convenient and reliable method to promote osteogenesis and angiogenesis simultaneously, thereby effectively promoting tendon–bone healing. Methods The amorphous calcium phosphate (ACP) nanoparticles with dual biological activities of osteogenesis and angiogenesis were prepared by a simple low-temperature aqueous solution method using adenosine triphosphate (ATP) as an organic phosphorus source. The activities of osteogenesis and angiogenesis and the effect on the tendon–bone healing of ACP nanoparticles were tested in vitro and in a rat model of acute RCT. Results The ACP nanoparticles with a diameter of tens of nanometers were rich in bioactive adenosine. In vitro, we confirmed that ACP nanoparticles could enhance osteogenesis and angiogenesis. In vivo, radiological and histological evaluations demonstrated that ACP nanoparticles could enhance bone and blood vessels formation at the tendon–bone junction. Biomechanical testing showed that ACP nanoparticles improved the biomechanical strength of the tendon–bone junction and ultimately promoted tendon–bone healing of rotator cuff. Conclusions We successfully confirmed that ACP nanoparticles could promote tendon–bone healing. ACP nanoparticles are a promising biological nanomaterial in augmenting tendon–bone healing. Graphic abstract
研究领域:
生物材料
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骨科
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纳米技术
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 42
·6564-6575
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IF 5.047
Wei Song,Zhijie Ma,Chongyang Wang,Haiyan Li,Yaohua He
Reconstructing the native structure of the tendon-to-bone insertion site (enthesis) in rotator cuff repair has always been a great challenge for orthopedic surgeons. Difficulty arises mainly due to the limited enthesis regenerative capability and severe inflammatory cell infiltration, which result in fibrovascular scar formation instead of native cartilage-like enthesis. Therefore, tissue engineering scaffolds with pro-chondrogenic and immunomodulatory capabilities may offer a new strategy for native enthesis regeneration. In this study, melatonin-loaded aligned polycaprolactone (PCL) electrospun fibrous membranes were fabricated. The sustained release of melatonin from this membrane significantly promoted the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) in a long-term chondroid pellet model. After the membranes were implanted in a rat acute rotator cuff tear model, melatonin-loaded PCL membranes inhibited macrophage infiltration in the tendon-to-bone interface at the early healing phase, increasing chondroid zone formation, promoting collagen maturation, decreasing fibrovascular tissue formation and eventually improving the biomechanical strength of the regenerated enthesis. Taken together, melatonin-loaded PCL membranes possess great clinical application potential for tendon-to-bone healing.
研究领域:
骨科
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组织工程
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生物材料
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干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Lang Bai,Qian Han,Zijie Meng,Baojun Chen,Xiaoli Qu,Meiguang Xu,Yanwen Su,Zhennan Qiu,Yuan Xue,Jiankang He,Jing Zhang,Zhanhai Yin
Substantial challenges remain in constructing the native tendon-to-bone interface for rotator cuff healing owing to the enthesis tissues' highly organized structural and compositional gradients. Herein, we propose to bioprint living tissue constructs with layer-specific growth factors (GFs) to promote enthesis regeneration by guiding the zonal differentiation of the loaded stem cells in situ . The sustained release of tenogenic, chondrogenic, and osteogenic GFs was achieved via microsphere-based delivery carriers embedded in the bioprinted constructs. Compared to the basal construct without GFs, the layer-specific tissue analogs realized region-specific differentiation of stem cells in vitro . More importantly, bioprinted living tissue constructs with layer-specific GFs rapidly enhanced the enthesis regeneration in a rabbit rotator cuff tear model in terms of biomechanical restoration, collagen deposition, and alignment, showing gradient interface of fibrocartilage structures with aligned collagen fibrils and an ultimate load failure of 154.3 ± 9.5 N resembling those of native enthesis tissues in 12 weeks. This exploration provides a feasible strategy to engineer living tissue constructions with region-specific differentiation potentials for the functional repair of gradient enthesis tissues. Statement of significance Previous studies that employed acellular layer-specific scaffolds or stem cells for the reconstruction of the rotator cuff faced challenges due to their insufficient capability to rebuild the anisotropic compositional and structural gradients of native enthesis tissues. This manuscript proposed a living tissue construct with layer-specific, GFs-loaded µS, which can direct in situ and region-specific differentiation of the embedded stem cells to tenogenic, chondrogenic, and osteogenic lineages for functional regeneration of the enthesis tissues. This bioprinted living tissue construct with the unique capability to reduce fibrovascular scar tissue formation and simultaneously facilitate enthesis tissue remodeling might provide a promising strategy to repair complex and gradient tissues in the future.
研究领域:
组织工程
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生物医学工程
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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
ACS Applied Materials & Interfaces
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2023
·
IF 9.5
Cancan Du,Ruiqi Wu,Wenqiang Yan,Jingchao Fang,Wenli Dai,Yiqun Wang,Jin Cheng,Xiaoqing Hu,Yingfang Ao,Xiaolong Liang,Zhenlong Liu
Rotator cuff tear (RCT) is a prevalent shoulder injury that poses challenges for achieving continuous and functional regeneration of the tendon-to-bone interface (TBI). In this study, we controlled the delivery of growth factors (GFs) from liposomal nanohybrid cerasomes by ultrasound and implanted three-dimensional printed polycaprolactone (PCL) scaffolds modified with polydopamine loaded with bone marrow mesenchymal stem cells (BMSCs) to repair tears of the infraspinatus tendon in a lapine model. Direct suturing (control, CTL) was used as a control. The PCL/BMSC/cerasome (PBC) devices are sutured with the enthesis of the infraspinatus tendon. The cerasomes and PCL scaffolds are highly stable with excellent biocompatibility. The roles of GFs BMP2, TGFβ1, and FGF2 in tissue-specific differentiation are validated. Compared with the CTL group, the PBC group had significantly greater proteoglycan deposition (P = 0.0218), collagen volume fraction (P = 0.0078), and proportions of collagen I (P = 0.0085) and collagen III (P = 0.0048). Biotin-labeled in situ hybridization revealed a high rate of survival for transplanted BMSCs. Collagen type co-staining at the TBI is consistent with multiple collagen regeneration. Our studies demonstrate the validity of biomimetic scaffolds of TBI with BMSC-seeded PCL scaffolds and GF-loaded cerasomes to enhance the treatment outcomes for RCTs.
研究领域:
生物医学工程
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组织工程
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干细胞研究
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骨科手术
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
·
2024
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IF 5.5
Xiaomei Dai,Meijuan Yuan,Yuxia Yang,Mengbo Dang,Jian Yang,Junli Shi,Dianwei Liu,Mingjun Li,Hang Yao,Wenyong Fei
The tendon-bone interface heals through scar tissue, while the lack of a natural interface gradient structure and collagen fibre alignment leads to the occurrence of retearing. Therefore, the promotion of tendon healing has become the focus of regenerative medicine. The purpose of this study was to develop a gradient COL1/ hydroxyapatite (HAp) biomaterial loaded with human amniotic mesenchymal stem cells (hAMSCs). The performance of common cross-linking agents, Genipin, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), and dual cross-linked materials were compared to select the best cross-linking mechanism to optimize the biological and mechanical properties of the scaffold. The optimal COL1/HAp-loaded with hAMSCs were implanted into the tendon-bone rotator cuff interfaces in rats and the effect on the tendon-bone healing was assessed by micro-CT, histological analysis, and biomechanical properties. The results showed that Genipin and EDC/NHS dual cross-linked COL1/HAp had good biological activity and mechanical properties and promoted the proliferation and differentiation of hAMSCs. Animal experiments showed that the group using a scaffold loaded with hAMSCs had excellent continuity and orientation of collagen fibers, increased fibrocartilage and bone formation, and significantly higher biomechanical functions than the control group at the interface at 12 weeks post operation. This study demonstrated that dual cross-linked gradient COL1/HAp-loaded hAMSCs could promote interface healing, thereby providing a feasible strategy for tendon-bone interface regeneration.
研究领域:
再生医学
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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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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2016
·Vol. 4
·期 45
·7259-7269
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IF 4.872
Yaying Sun,Fei Han,Peng Zhang,Yunlong Zhi,Jianjun Yang,Xiaohan Yao,Hui Wang,Chao Lin,Xuejun Wen,Jiwu Chen,Peng Zhao
Massive rotator cuff tears (MRCTs) are difficult to repair because of the retraction and poor mobility of torn tendons. In the current study, co-electrospun dual nano-scaffolds of poly(lactic-co-glycolic acid)/collagen I-polycaprolactone/nanohydroxyapatite (PLGA/Col-PCL/nHA) were fabricated and used to bridge MRCTs of infraspinatus tendons in a rabbit model. PLGA–PCL served as a control. The PLGA or the PLGA/Col sides of the dual scaffolds connected the tendon stumps. The PCL or PCL/nHA side was inserted into the bone tunnel at the insertion of the infraspinatus tendon. Fibroblasts showed higher viability and collagen secretion when seeded on a PLGA/Col scaffold compared to a PLGA scaffold. Osteoblasts seeded on a PCL/nHA scaffold grew better with higher mineralization than on a PCL scaffold. Histologically, collagen regenerated along PLGA scaffolds, but showed poor ingrowth to scaffolds compared with the PLGA/Col group. Newly formed bone was observed on the PCL scaffold, but was less than that on the PCL/nHA scaffold. At 6 weeks post repair, the regenerated tendon in both groups had similar maximum load to failure and ultimate stress but significantly lower stiffness in the PLGA–PCL group and a higher cross-sectional area in the PLGA/Col-PCL/nHA group compared with normal values. At 12 weeks, the maximum failure load, ultimate stress and cross-sectional areas of the regenerated tendon in the PLGA/Col-PCL/nHA group were significantly higher than in the PLGA–PCL and normal groups. The biomechanical properties of the PLGA–PCL group were similar to normal except for a larger cross-sectional area. Our data showed that the co-electrospun dual nano-scaffolds are promising in bridging MRCTs. Doping with Col and nHA further strengthens tissue regeneration.
研究领域:
生物医学工程
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组织工程
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2024
·
IF 6.1
Zhonglian Wu,Jian Yang,Hui Chong,Xiaomei Dai,Haidi Sun,Junli Shi,Meijuan Yuan,Dianwei Liu,Mengbo Dang,Hang Yao,Wen-Yong Fei
Rotator cuff tear repair poses significant challenges due to the complex gradient interface structure. In the face of disease-related disruptions in the tendon-bone interface (TBI), the strategy of constructing a biomimetic scaffold is a promising avenue. A novel 3D-printed rotator cuff scaffold loaded adipose stem cells (ADSCs), bone morphogenetic protein-2 (BMP-2), and collagen type I (COL I). The efficiency of the slow-release BMP-2 design depended on the dopamine-hyaluronic acid (HAD) and BMP-2 reaction. The cumulative release of BMP-2 was 44.97% ± 5.45% at 4 weeks. The 3D-printed bilayer scaffold, incorporating COL I and BMP-2, effectively promoted the differentiation of ADSCs into osteogenic, tenogenic, and chondrogenic lineages in vitro. The combination of 3D-printed bioactive scaffolds and ADSCs demonstrated a superior repair effect on rotator cuff injuries in vivo. Therefore, these findings indicated that the 3D-printed biomimetic scaffold loaded with ADSCs and BMP-2 holds potential as a promising graft for TBI healing.
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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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Extreme Manufacturing
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2024
·Vol. 6
·期 5
·055003
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IF 16.1
Lang Bai,Meiguang Xu,Zijie Meng,Zhennan Qiu,Jintao Xiu,Baojun Chen,Qian Han,Qiaonan Liu,Pei He,Nuanyang Wen,Jiankang He,Jing Zhang,Zhanhai Yin
The rotator cuff tear has emerged as a significant global health concern. However, existing therapies fail to fully restore the intricate bone-to-tendon gradients, resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues. Herein, a tri-layered core–shell microfibrous scaffold with layer-specific growth factors (GFs) release is developed using coaxial electrohydrodynamic (EHD) printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair. Stromal cell-derived factor-1 (SDF-1) is loaded in the shell, while basic fibroblast GF, transforming GF-beta, and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner. Correspondingly, the tri-layered microfibrous scaffolds have a core–shell fiber size of (25.7 ± 5.1) μm, with a pore size sequentially increasing from (81.5 ± 4.6) μm to (173.3 ± 6.9) μm, and to (388.9 ± 6.9 μm) for the tenogenic, chondrogenic, and osteogenic instructive layers. A rapid release of embedded GFs is observed within the first 2 d, followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks. The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte, chondrocyte, and osteocyte phenotypes in vitro. When implanted in vivo, the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients. Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.
研究领域:
组织工程
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再生医学
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生物医学材料
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骨科
✓ 已验证
产品关联
DOI
高影响因子
Small
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2024
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IF 13
Xuancheng Zhang,Wei Song,Yang Liu,Kang Han,Yuxu Wu,Eunshinae Cho,Zhaoyi Fang,Lianghua Jiang,Yihe Hu,Xuesong Zhu,Jia Jiang,Xiaoqiao Huangfu,Jinzhong Zhao
The re-tear rate of rotator cuff tears (RCT) after surgical repair is high, especially in aged patients with chronic tears. Senescent tendon stem cells (s-TSCs) generally exist in aged and chronically torn rotator cuff tendons and are closely associated with impaired tendon-to-bone healing results. The present study found a positive feedback cross-talk between s-TSCs and macrophages. The conditioned medium (CM) from s-STCs can promote macrophage polarization mainly toward the M1 phenotype, whose CM reciprocally accelerated further s-TSC senescence. Additional healthy tendon stem-cells derived exosomes (h-TSC-Exos) can break this positive feedback cross-talk by skewing macrophage polarization from the M1 phenotype to the M2 phenotype, attenuating s-TSCs senescence. S-TSC senescence acceleration or attenuation effects induced by M1 or M2 macrophages are associated with the inhibition or activation of the bone morphogenetic protein 4 signaling pathway following RNA sequencing analysis. Using an aged-chronic rotator cuff tear rat model, it is found that h-TSC-Exos can shift the microenvironment in the tendon-to-bone interface from a pro-inflammatory to an anti-inflammatory type at the acute postoperative stage and improve the tendon-to-bone healing results, which are associated with the rejuvenated s-TSCs. Therefore, this study proposed a potential strategy to improve the healing of aged chronic RCT.
CAS / MDL:
研究领域:
骨科
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干细胞生物学
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组织工程
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再生医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Chengzhi Liang,Fanrong Ai,Huajun Pan,Fengyang Cui,Hang Fu,PinKai Wang,Yudan Zhu,Weixiang Xiong,Dewei Qiu,Jun Tao
A rotator cuff tear (RCT) is a common sports injury. Current surgical interventions frequently result in suboptimal healing and fail to regenerate the complex, heterogeneous tendon–bone interface. Piezoelectric materials, which convert ultrasound-derived micromechanical energy into electrical signals, offer a potential means to overcome the limitations of conventional electrical stimulation therapies for musculoskeletal tissue repair. Moreover, active and controlled drug release has become increasingly essential in modern regenerative strategies. We developed a Janus bilayered fibrous scaffold (KZP@PS/PSPM) with dual-phase induction and immunomodulatory capabilities using electrospinning and oxidative polymerization. Under ultrasonic exposure, the underlying PSPM fibrous membrane transduces mechanical energy into electrical signals that stimulate osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). Concurrently, the upper KZP@PS layer converts mechanical energy into electrical signals, activating the electrochemical reduction of polyaniline (PANI) and inducing a stress-responsive release of KZF, which secretes zinc ions (Zn 2 ⁺) and kartogenin (KGN) to promote immunomodulation and chondrogenesis. This process further enhances osteogenic and chondrogenic differentiation through upregulation of the ERK1 and PI3K–Akt signaling pathways. In a rotator cuff injury model, the KZP@PS/PSPM composite scaffold significantly reduced early inflammatory markers and markedly improved tendon-to-bone healing. By synergizing “ultrasound–electricity” with “electricity–drug release,” this Janus bilayer scaffold enables biphasic induction and immunomodulation, offering a novel strategy for addressing the complex challenges of tendon–bone interface regeneration.
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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肌肉骨骼修复
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智能药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）