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Biomaterials Advances · 2024 · IF 5.5

Dual cross-linked COL1/HAp bionic gradient scaffolds containing human amniotic mesenchymal stem cells promote rotator cuff tendon–bone interface healing

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.

CAS / MDL: 51-79-6 6902-77-8
研究领域: 再生医学 · 组织工程 · 生物材料 · 干细胞生物学 · 骨科
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AMERICAN JOURNAL OF SPORTS MEDICINE · 2025 · IF 4.5

An Aligned-to-Random PLGA/Col1-PLGA/nHA Bilayer Electrospun Nanofiber Membrane Enhances Tendon-to-Bone Healing in a Murine Model

Baoyun Xu,Yunjiao Wang,Gang He,Xu Tao,Shang Gao,Mei Zhou,Yuzhen Tang,Kang-lai Tang,Lin Guo,Wan Chen

Background:The challenge of achieving effective tendon-to-bone healing remains a significant concern in sports medicine, necessitating further exploration. Biomimetic electrospun nanomaterials present promising avenues for improving this critical healing process.Purpose:To investigate the biological efficacy of a novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer electrospun nanofiber membrane in facilitating tendon-to-bone healing.Study Design:Controlled laboratory study.Methods:The bilayer membrane’s composition, combining PLGA/Col1 for tendon attachment and PLGA/nHA for bone integration, was examined using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical testing. Positioned between the Achilles tendon and bone, its design aimed for harmonious integration with both types of tissue. In vitro, biocompatibility, cell adhesion, and proliferation of the biomaterial were evaluated using live/dead staining and the CCK-8 assay. Collagen secretion and mineralization were measured for 2 cell types. In vivo, tendon-to-bone insertion samples harvested from mice were analyzed: micro–computed tomography assessed bone formation; histological staining evaluated chondrogenesis, tendinogenesis, and the 4-layer structure of the insertion; and biomechanical testing measured insertion strength. Real-time polymerase chain reaction identified genes involved in tendon-to-bone healing, and transcriptome analysis elucidated the underlying cellular and molecular mechanisms.Results:The optimal composition was determined as 10% 3:1 for aligned PLGA/Col1 and 9% 5:1 for PLGA/nHA. Coculture showed minimal cell death, firm cell adherence, and steady proliferation, with PLGA/Col1 enhancing collagen secretion. In vivo, the material promoted bone and cartilage formation and improved tendon-to-bone interface strength. Transcriptome analysis indicated links to TNF and NF-κB pathways and to genes IL-1β, ADAM8, and EGR2.Conclusion:The novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer nanofiber membrane outperformed other materials in both in vitro and in vivo evaluations, significantly enhancing tendon-to-bone healing. It notably improved cartilage and bone formation, tendon maturation, and biomechanical strength at the surgical interface. These effects may be associated with the TNF and NF-κB pathways and with the genes IL-1β, ADAM8, and EGR2.Clinical Relevance:This study introduces a biomimetic nanofiber membrane enhancing tendon-to-bone healing, which is crucial for sports medicine. Its efficacy in improving healing outcomes, including bone and cartilage formation and biomechanical strength, could significantly lower failure rates in surgical procedures such as rotator cuff repair and anterior cruciate ligament reconstruction. This advancement offers promising implications for patient recovery and the effectiveness of surgical interventions in tendon-to-bone injuries.

研究领域: 运动医学 · 组织工程 · 生物材料科学 · 骨科 · 生物医学工程
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JOURNAL OF MATERIALS RESEARCH · 2021 ·Vol. 36 ·期 9 ·1866-1882 · IF 3.089

Silicon nitride as a potential candidate for dental implants: Osteogenic activities and antibacterial properties

Wu Jin,Liu Yajing,Zhang Hao,Wu Yizhen,Chu Zhuangzhuang,Wu Qirong,Lu Mengmeng,Tang Chunbo

Abstract In this study, we presented that human bone mesenchymal stem cells (hBMSCs) showed superior adhesion and proliferation behaviors on polished silicon nitride (Si 3 N 4 ). Also, compared to Ti and ZrO 2 , Si 3 N 4 enhanced the osteogenic activities of hBMSCs indicated by increases in alizarin red S (ARS) staining, Ca 2+ concentration, and mRNA expression of RUNX2, OPN, OCN, and COL1. Furthermore, colony formation assays demonstrated significantly better antibacterial activities against oral pathogens Porphyromonas gingivalis (Pg), Staphylococcus aureus (SA), and Escherichia coli ( E. coli ) on Si 3 N 4 surface than Ti and ZrO 2 . Live/dead bacterial staining showed a large amount of dead Pg on Si 3 N 4 surfaces. The fact that Si 3 N 4 demonstrated advantages in osteogenic and antibacterial activities over Ti and ZrO 2 might be a reason for its potential use as non-metallic dental implant materials. However, more detailed studies with resolution techniques and preclinical studies are needed to confirm the Si 3 N 4 ’s osteogenic and antibacterial properties. Trial registration number PJ2019-066-001; date of registration: Jun 2019. Graphic abstract

CAS / MDL: 123-03-5
研究领域: 牙科学 · 生物材料 · 细胞生物学 · 微生物学
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Biomaterials Science · 2024 · IF 5.8

Fast bone regeneration using injectable fully biomimetic organoids with biomineralized and organic microenvironments

Runquan Zheng,Ning Zhang,Songbo Mao,Jiawei Li,Xuesong Yan,Guichun Zhang,Yongxian Zhang,Xianhu Yue

Bone defects and congenital bone deficiencies are common clinical conditions. However, conventional non-degradable artificial materials often lead to serious complications, such as severe infections and material displacement. The emergence of tissue engineering and the organoids concept presents a promising approach for the repair of bone defects, facilitating physiological reconstruction while minimizing complications. Nevertheless, previous studies have not developed injectable organoids that incorporates fully mineralized and organic microenvironments to achieve rapid osteogenesis and convenient application in bone regeneration. Therefore, it is imperative to devise an effective strategy to address these challenges. This study first prepared injectable GL scaffolds with varying concentrations and identified the optimal GL concentration for osteogenesis through systematic evaluation of osteogenic efficiency. Subsequently, inorganic salts of native bone (NBIS) and extracellular matrix from the periosteum (pECM) were integrated into the optimal GL scaffold to create an injectable scaffold featuring biomimetic mineralized and organic microenvironments. This scaffold was further utilized for in vitro analysis of osteogenic mechanisms and injected subcutaneously into rabbits for only four weeks to assess its osteogenic efficacy in vivo. The results indicated that the incorporation of NBIS and pECM significantly enhanced osteogenic efficacy by actively regulating ossification and ECM-receptor interaction signaling pathways, as well as upregulating RUNX2, ALP, COL1, and LAMA. This study introduces a promising injectable strategy for rapid osteogenesis using fully mineralized and organic biomimetic organoids.

研究领域: 组织工程 · 骨再生 · 生物材料 · 医学生物技术
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