ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Zijian Li,Hufei Wang,Xiao Liu,Zhengyang Chang,Jianpeng Gao,Junyao Cheng,Licheng Zhang,Xing Wang,Ming Li,Jianheng Liu,Peifu Tang
Achilles tendon injuries present significant clinical challenges due to limited regenerative capacity and frequent adhesion formation. Here, we report a melatonin-loaded Janus fibrous membrane (MLT@JFM) that mimics the native paratenon’s structure and function to promote scarless tendon healing. The biomimetic membrane consists of an inner methacrylated silk fibroin (SFMA) layer that promotes tendon stem cell functions and an outer melatonin-loaded polycaprolactone methacryloyl (PCLMA) layer that prevents adhesion formation. Through photo-cross-linking and structural interlocking, MLT@JFM achieves excellent mechanical properties and stable fixation around injured tendons. In vitro studies demonstrate that MLT@JFM effectively scavenges reactive oxygen species, modulates macrophage polarization, and maintains tendon stem cell phenotype under inflammatory conditions. In a rat Achilles tendon injury model, MLT@JFM significantly enhances functional recovery and biomechanical properties while preventing adhesion formation. Transcriptomic analysis reveals that MLT@JFM promotes scarless healing through synergistic regulation of oxidative-inflammatory cascades and the enhancement of tissue regeneration. This study presents MLT@JFM as a promising therapeutic strategy for tendon repair and provides new insights into biomaterial-mediated tissue regeneration.
研究领域:
生物材料
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组织工程
·
再生医学
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纳米医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Ke Yao,Shang Lv,Xinjie Zhang,Kangning Shen,Yuewei Chen,Zhiyong Ma,Yong He
Multi-scale scaffolds with biomimetic extracellular matrix (ECM) structures are crucial for regenerative repair. Nevertheless, the intricate nature of nanostructures presents challenges when attempting to efficiently manufacture on a larger scale while maintaining bionics at the nanoscale. Here, a multiscale scaffold with hierarchical structures is designed to address these challenges, which can be biomimetic tendons from macro and micro to nanoscale. The multiscale biomimetic tendon (MBT) scaffold consists of a shell and core. The porous shell replicates the structure of a tendon sheath, offers mechanical support, and facilitates ease of sewing. The core scaffold comprises micro-scale wave fibers with a nanohybrid Shish-Kebab structure, designed to mimic the collagen fiber and fibril found in tendons. Additionally, the MBT scaffold demonstrates a strong tensile strength of 6.94 MPa and is shown to enhance the adhesion and proliferation of tendon stem/progenitor cells (TSPCs). Animal experiments have shown that the MBT scaffold can be surgically sutured in the tendon defect area to facilitate mechanical transduction and accelerate the regeneration of tendon tissue. The research combines the precise manufacturing of nano-structures with efficient macro-structure fabrication. It addresses the shortcomings of the disorder nanostructures and offers a fresh approach to creating multi-scale bionic scaffolds.
研究领域:
生物材料学
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组织工程
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再生医学
✓ 已验证
DOI
高影响因子
Applied Materials Today
·
2025
·
IF 6.9
Xinyan Chen,Xiao Yu,Hao Feng,Panpan Shang,Muhammad Shafiq,Zhengchao Yuan,Cheng Li,Zewen Wang,Zhenchao Liu,Yuan Yao,Mohamed EL-Newehy,Meera Moydeen Abdulhameed,Yan Xiong,Yuan Xu,Xiumei Mo
The effectiveness of tendon regeneration is impeded by an excessive inflammatory response as well as uncontrolled proliferation of fibroblasts. Transplantation of tendon substitutes which can balance inflammatory response while constrict aberrant proliferation of fibroblasts is a key to promote functional tendon regeneration. The objective of this study was to design electrospun tetrandrine-loaded polylactic acid/silk fibroin (PLLA/SF) nanofibers and then fabricate them into knitted scaffolds. Briefly PLLA micron yarns were coated with PLLA/SF nanofibers and processed into knitted scaffolds. The incorporation of tetrandrine into fibers resulted in a significant suppression of fibroblast proliferation ( p < 0.05) and promoted macrophage polarization into anti-inflammatory phenotypes, with a CD206/CD68 ratio increase of 2.5-fold compared to the control. Additionally, knitted scaffolds delayed the inflammatory response and enhanced collagen production at the repair site in vivo . Taken together, our approach of simultaneously harnessing structural and biological cues in the form of an antiproliferative and anti-inflammatory therapeutic alongside PLLA/SF-coated nanoyarns afforded knitted scaffolds. The bifunctional regulation of tetrandrine simultaneously addressing inflammation resolution and fibrotic inhibition represents a strategic advance over existing mono-functional drug-loaded scaffolds.
研究领域:
生物医学工程
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-17
·
IF 10.2
Ren Xunshan,Zhuang Huangming,Zhang Yuelong,Zhou Panghu
Background Tendon injuries have a high incidence and limited treatment options. Stem cell transplantation is essential for several medical conditions like tendon injuries. However, high local concentrations of reactive oxygen species (ROS) inhibit the activity of transplanted stem cells and hinder tendon repair. Cerium oxide nanoparticles (CeONPs) have emerged as antioxidant agents with reproducible reducibility. Results In this study, we synthesized polyethylene glycol-packed CeONPs (PEG-CeONPs), which were loaded into the human umbilical cord mesenchymal stem cells (hUCMSCs) to counteract oxidative damage. H 2 O 2 treatment was performed to evaluate the ROS scavenging ability of PEG-CeONPs in hUCMSCs. A rat model of patellar tendon defect was established to assess the effect of PEG-CeONPs-carrying hUCMSCs in vivo. The results showed that PEG-CeONPs exhibited excellent antioxidant activity both inside and outside the hUCMSCs. PEG-CeONPs protect hUCMSCs from senescence and apoptosis under excessive oxidative stress. Transplantation of hUCMSCs loaded with PEG-CeONPs reduced ROS levels in the tendon injury area and facilitated tendon healing. Mechanistically, NFκB activator tumor necrosis factor α and MAPK activator dehydrocrenatine, reversed the therapeutic effect of PEG-CeONPs in hUCMSCs, indicating that PEG-CeONPs act by inhibiting the NFκB and MAPK signaling pathways. Conclusions The carriage of the metal antioxidant oxidase PEG-CeONPs maintained the ability of hUCMSCs in the injured area, reduced the ROS levels in the microenvironment, and facilitated tendon regeneration. The data presented herein provide a novel therapeutic strategy for tendon healing and new insights into the use of stem cells for disease treatment. Graphical Abstract
研究领域:
生物医学工程
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干细胞生物学
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组织工程
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Jianping Zhao,Di Zhang,Qiumei Lan,Gang Zhong,Yisi Liu,Nathaniel Holwell,Xiang Wang,Jinzhi Meng,Jun Yao,Brian G. Amsden,Yin Yu,Fei Chen
Current engineered synthetic scaffolds fail to functionally repair and regenerate ruptured native tendon tissues, partly because they cannot satisfy both the unique biological and biomechanical properties of these tissues. Ideal scaffolds for tendon repair and regeneration need to provide porous topographic structures and biological cues necessary for the efficient infiltration and tenogenic differentiation of embedded stem cells. To obtain crimped and porous scaffolds, highly aligned poly(l-lactide) fibers were prepared by electrospinning followed by postprocessing. Through a mild and controlled hydrogen gas foaming technique, we successfully transformed the crimped fibrous mats into three-dimensional porous scaffolds without sacrificing the crimped microstructure. Porcine derived decellularized tendon matrix was then grafted onto this porous scaffold through fiber surface modification and carbodiimide chemistry. These biofunctionalized, crimped, and porous scaffolds supported the proliferation, migration, and tenogenic induction of tendon derived stem/progenitor cells, while enabling adhesion to native tendons. Together, our data suggest that these biofunctionalized scaffolds can be exploited as promising engineered scaffolds for the treatment of acute tendon rupture.
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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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
Biomaterials Science
·
2021
·Vol. 10
·期 3
·753-769
·
IF 6.843
Zhiwei Yin,Lu Sun,Liyang Shi,Hemin Nie,Jianwu Dai,Can Zhang
Poor tendon repair remains a clinical problem due to the difficulties in replicating the complex multiscale hierarchical structure of native tendons. In this work, a bioinspired fibrous scaffold with bimodal micro-nanofibers and a teno-inductive aligned topography was developed to replicate microscale collagen fibers and nanoscale collagen fibrils that compose native tendons. The results showed indicated that the combination of micro- and nanofibers enhanced the mechanical properties. Furthermore, their biological performance was assessed using tendon stem/progenitor cells (TSPCs). Micro-nanofibers induced a higher cell aspect ratio and enhanced the tenogenic differentiation of TSPCs compared to micro- and nanocontrols. Interestingly, it was observed that scaffold nanotopography and microstructures promoted tenogenesis via activating the TGF-β/Smad2/3-mediated signaling pathway. The in situ implantation study confirmed that micro-nanofibrous scaffolds promoted the structural and mechanical properties of the regenerated Achilles tendon. Overall, our study shows that the bimodal micro-nanofibrous scaffold developed here presents a promising potential to improve the outcomes of tendon tissue engineering.
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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细胞生物学
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机械工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2019
·
IF 8.013
Tian Tu,Yanbing Shen,Xiansong Wang,Wenjie Zhang,Guangdong Zhou,Yanzhong Zhang,Wenbo Wang,Wei Liu
Proper niche environment is the key factor for mesenchymal stem cells (MSCs) involved tendon-lineage differentiation and regeneration. In the present study, soluble tendon derived extracellular matrix (sTECM) was used to modify aligned electrospun fibers with acid neutralizing effect in order to create an optimal niche environment for tendon regeneration, and its efficacy was evaluated using mouse MSC tenogenic differentiation in vitro and rat Achilles tendon regeneration in vivo . The results showed that sTECM modified ultrafine fibers were more cytocompatible and capable of inducing a predominant tenogenic phenotype of mouse MSCs with the enhanced expression of tendon markers including scleraxis , tenomodulin , collagen III , mohawk homeobox , decorin , fibromodulin and biglycan . By contrast, pure sTECM components led to enhanced multi-lineage differentiation of mouse MSCs including tenogenic lineage. This inductive effect was further enhanced when unilateral mechanical loading was applied in vivo. Moreover, the implantation of sTECM modified scaffold created an ideal niche environment including bioactive sTECM components, topological and mechanical signals, upon in vivo implantation for in situ tendon regeneration. As the results, sTECM modified scaffold in comparison with the non-modified one regenerated higher quality tendon tissue with the features of more mature tissue structure, better tissue organization, cell density and alignment as well as better collagen ultrastructure. Quantitative analysis demonstrated significantly bigger collagen fibril diameter, stronger mechanical property and better tissue grading score and higher expression levels of tenogenic markers when compared to those of control scaffold (p < 0.05). This study demonstrated that sTECM modified pH-neutral ultrafine fibers may represent a novel bioactive scaffold for in situ tendon regeneration, which deserves further investigation in large animals.
研究领域:
组织工程
·
生物材料
·
干细胞生物学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xiao Yu,Chao Li,Jie Cui,Hao Feng,Yangfan Ding,Jiahui Song,Pengfei Cai,Liang Chen,Mohamed EL-Newehy,Meera Moydeen Abdulhameed,Xiumei Mo,Yu Han,Binbin Sun
Achilles tendon sleeve avulsions often involve tissue defects. Standard bone tunnel fixation risks tunnel enlargement, inflammation, and graft failure. Native tendon and bone tissue exhibit inherent bioelectrical properties whose disruption impedes healing. To address these, the study developed electroactive, anti-inflammatory sutures featuring a strong polylactic acid (PLA) micron yarn core and a conductive poly(3,4-ethylenedioxythiophene)/hydroxyethyl cellulose/glycerol/chondroitin sulfate/PLA (PEDOT/HEC/glycerol/CS/PLA) nanofibrous shell. A novel synthesis strategy enabled EDOT polymerization templated by HEC, eliminating the need for poly(styrene sulfonate) (PSS), oxidants, or catalysts and allowing direct electrospinning. In vitro, it can regulate macrophage polarization and enhance tenocytes and bone marrow mesenchymal stem cell (BMSCs) proliferation and differentiation. In a rabbit Achilles tendon avulsion model, the suture enables secure tendon-to-bone fixation via calcaneal bone tunnels. At 12 weeks post-operation, the suture exerts anti-inflammatory effects by modulating CD206/CD86 expression. Electroactive suture significantly enhances tendon regeneration and bone formation within the tunnels, and achieves robust tendon-to-bone integration at the interface, markedly improving fixation stability. In summary, this electroactive, anti-inflammatory suture effectively promotes tendon-bone regeneration for repairing Achilles tendon sleeve avulsions.
研究领域:
生物材料
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组织工程
·
再生医学
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生物医学工程
·
骨科手术
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纳米技术
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高分子科学
·
免疫调节
✓ 已验证
产品关联
DOI
高影响因子
npj Regenerative Medicine
·
2023
·Vol. 8
·期 1
·1-18
·
IF 7.2
Tu Tian,Shi Yuan,Zhou Boya,Wang Xiaoyu,Zhang Wenjie,Zhou Guangdong,Mo Xiumei,Wang Wenbo,Wu Jinglei,Liu Wei
Our previous work demonstrated the tendon-derived extracellular matrix (ECM) extracts as vital niches to specifically direct mesenchymal stem cells towards tenogenic differentiation. This study aims to further define the effective ECM molecules capable of teno-lineage induction on human adipose-derived stem cells (hASCs) and test their function for tendon engineering. By detecting the teno-markers expression levels in hASCs exposed to various substrate coatings, collagen I (COL1) and fibromodulin (FMOD) were identified to be the key molecules as a combination and further employed to the modification of poly(L-lactide- co -ε-caprolactone) electrospun nanoyarns, which showed advantages in inducting seeded hASCs for teno-lineage specific differentiation. Under dynamic mechanical loading, modified scaffold seeded with hASCs formed neo-tendon in vitro at the histological level and formed better tendon tissue in vivo with mature histology and enhanced mechanical properties. Primary mechanistic investigation with RNA sequencing demonstrated that the inductive mechanism of these two molecules for hASCs tenogenic differentiation was directly correlated with positive regulation of peptidase activity, regulation of cell-substrate adhesion and regulation of cytoskeletal organization. These biological processes were potentially affected by LOC101929398/has-miR-197-3p/TENM4 ceRNA regulation axis. In summary, COL1 and FMOD in combination are the major bioactive molecules in tendon ECM for likely directing tenogenic phenotype of hASCs and certainly valuable for hASCs-based tendon engineering.
研究领域:
组织工程
·
干细胞生物学
·
再生医学
·
生物医学工程
·
力学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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