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Meticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regeneration. 精心设计的三维打印支架具有微结构和可控肽释放功能,可促进骨再生。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.007
Jin Yang, Kanwal Fatima, Xiaojun Zhou, Chuanglong He

The repair of large load-bearing bone defects requires superior mechanical strength, a feat that a single hydrogel scaffold cannot achieve. The objective is to seamlessly integrate optimal microarchitecture, mechanical robustness, vascularisation, and osteoinductive biological responses to effectively address these critical load-bearing bone defects. To confront this challenge, three-dimensional (3D) printing technology was employed to prepare a polycaprolactone (PCL)-based integrated scaffold. Within the voids of 3D printed PCL scaffold, a methacrylate gelatin (GelMA)/methacrylated silk fibroin (SFMA) composite hydrogel incorporated with parathyroid hormone (PTH) peptide-loaded mesoporous silica nanoparticles (PTH@MSNs) was embedded, evolving into a porous PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL) scaffold. The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation. Compression testing unveiled an impressive strength of 17.81 ± 0.83 MPa for the composite scaffold. Additionally, in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium, revealing the superior cell migration and tube network formation. The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold. Furthermore, the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination, demonstrating enhanced osteogenic and angiogenic performance. This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering, providing a potential solution for effective bone defect repair.

修复大面积承重骨缺损需要超强的机械强度,这是单一水凝胶支架无法实现的。我们的目标是无缝整合最佳微结构、机械坚固性、血管化和骨诱导生物反应,以有效解决这些关键的承重骨缺损问题。为了应对这一挑战,我们采用三维(3D)打印技术制备了一种基于聚己内酯(PCL)的集成支架。在三维打印 PCL 支架的空隙中,嵌入了甲基丙烯酸酯明胶(GelMA)/甲基丙烯酸丝纤维素(SFMA)复合水凝胶,其中含有甲状旁腺激素(PTH)肽负载介孔二氧化硅纳米颗粒(PTH@MSNs),从而形成了多孔的 PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL)支架。通过细致的化学和物理表征,证实了制造这种具有定制分层结构的功能性支架的可行性。压缩测试显示,复合支架的强度达到了令人印象深刻的 17.81 ± 0.83 兆帕。此外,通过使用人脐静脉内皮细胞进行 Transwell 和管形成试验,对 PM@GS/PCL 支架的体外血管生成潜力进行了评估,结果表明其细胞迁移和管网形成性能优越。使用骨髓间充质干细胞进行的茜素红和碱性磷酸酶染色试验清楚地表明,这种支架具有强大的成骨分化特性。此外,还利用微计算机断层扫描和组织学检查在大鼠股骨缺损模型上研究了这种支架的骨修复潜力,结果表明它具有更强的成骨和血管生成性能。这项研究提出了一种用于骨组织工程的微环境匹配复合支架的制造策略,为有效修复骨缺损提供了一种潜在的解决方案。
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引用次数: 0
Advances in electrode interface materials and modification technologies for brain-computer interfaces. 脑机接口电极界面材料和改性技术的进展。
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.003
Yunke Jiao, Miao Lei, Jianwei Zhu, Ronghang Chang, Xue Qu

Recent advances in neuroelectrode interface materials and modification technologies are reviewed. Brain-computer interface is the new method of human-computer interaction, which not only can realise the exchange of information between the human brain and external devices, but also provides a brand-new means for the diagnosis and treatment of brain-related diseases. The neural electrode interface part of brain-computer interface is an important area for electrical, optical and chemical signal transmission between brain tissue system and external electronic devices, which determines the performance of brain-computer interface. In order to solve the problems of insufficient flexibility, insufficient signal recognition ability and insufficient biocompatibility of traditional rigid electrodes, researchers have carried out extensive studies on the neuroelectrode interface in terms of materials and modification techniques. This paper introduces the biological reactions that occur in neuroelectrodes after implantation into brain tissue and the decisive role of the electrode interface for electrode function. Following this, the latest research progress on neuroelectrode materials and interface materials is reviewed from the aspects of neuroelectrode materials and modification technologies, firstly taking materials as a clue, and then focusing on the preparation process of neuroelectrode coatings and the design scheme of functionalised structures.

综述了神经电极接口材料和改性技术的最新进展。脑机接口是人机交互的新方法,它不仅能实现人脑与外部设备之间的信息交换,还为脑相关疾病的诊断和治疗提供了一种全新的手段。脑机接口中的神经电极接口部分是脑组织系统与外部电子设备之间电、光、化学信号传输的重要区域,决定着脑机接口的性能。为了解决传统刚性电极柔韧性不足、信号识别能力不强、生物相容性不高等问题,研究人员从材料和改性技术两方面对神经电极接口进行了大量研究。本文介绍了神经电极植入脑组织后发生的生物反应,以及电极界面对电极功能的决定性作用。随后,从神经电极材料和改性技术两方面综述了神经电极材料和界面材料的最新研究进展,首先以材料为线索,然后重点介绍了神经电极涂层的制备工艺和功能化结构的设计方案。
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引用次数: 0
Comments on Innovative design of minimal invasive biodegradable poly(glycerol-dodecanoate) nucleus pulposus scaffold with function regeneration. 关于具有功能再生功能的微创生物可降解聚(甘油-十二酸酯)髓核支架的创新设计的评论。
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.010
Hao Zhou, Aimin Wu
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引用次数: 0
Harvest of functional mesenchymal stem cells derived from in vivo osteo-organoids. 收获来自体内骨组织的功能性间充质干细胞。
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.006
Shunshu Deng, Fuwei Zhu, Kai Dai, Jing Wang, Changsheng Liu

Bone marrow-derived mesenchymal stem cells (BM-MSCs) play a crucial role in stem cell therapy and are extensively used in regenerative medicine research. However, current methods for harvesting BM-MSCs present challenges, including a low yield of primary cells, long time of in vitro expansion, and diminished differentiation capability after passaging. Meanwhile mesenchymal stem cells (MSCs) recovered from cell banks also face issues like toxic effects of cryopreservation media. In this study, we provide a detailed protocol for the isolation and evaluation of MSCs derived from in vivo osteo-organoids, presenting an alternative to autologous MSCs. We used recombinant human bone morphogenetic protein 2-loaded gelatin sponge scaffolds to construct in vivo osteo-organoids, which were stable sources of MSCs with large quantity, high purity, and strong stemness. Compared with protocols using bone marrow, our protocol can obtain large numbers of high-purity MSCs in a shorter time (6 days vs. 12 days for obtaining passage 1 MSCs) while maintaining higher stemness. Notably, we found that the in vivo osteo-organoid-derived MSCs exhibited stronger anti-replicative senescence capacity during passage and amplification, compared to BM-MSCs. The use of osteo-organoid-derived MSCs addresses the conflict between the limitations of autologous cells and the risks associated with allogeneic sources in stem cell transplantation. Consequently, our protocol emerges as a superior alternative for both stem cell research and tissue engineering.

骨髓间充质干细胞(BM-MSCs)在干细胞治疗中发挥着重要作用,并被广泛用于再生医学研究。然而,目前收获骨髓间充质干细胞的方法面临挑战,包括原代细胞产量低、体外扩增时间长、传代后分化能力减弱等。同时,从细胞库中回收的间充质干细胞(MSCs)还面临着冷冻保存介质的毒性作用等问题。在这项研究中,我们提供了一种从体内骨组织中分离和评估间充质干细胞的详细方案,为自体间充质干细胞提供了一种替代方法。我们使用重组人骨形态发生蛋白 2 负载明胶海绵支架构建体内骨组织,这是一种稳定的间充质干细胞来源,具有数量多、纯度高、干性强等特点。与使用骨髓的方案相比,我们的方案能在更短的时间内获得大量高纯度的间充质干细胞(6 天比 12 天获得 1 期间充质干细胞),同时保持更高的干性。值得注意的是,我们发现,与骨髓间充质干细胞相比,体内骨组织来源的间充质干细胞在通过和扩增过程中表现出更强的抗复制衰老能力。骨组织来源间充质干细胞的使用解决了干细胞移植中自体细胞的局限性和异体来源相关风险之间的矛盾。因此,我们的方案成为干细胞研究和组织工程的最佳选择。
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引用次数: 0
Converging technologies in biomaterial translational research. 生物材料转化研究中的融合技术。
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.001
Long Bai, Jiacan Su
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引用次数: 0
Recent advances of medical polyhydroxyalkanoates in musculoskeletal system. 肌肉骨骼系统中医用聚羟基烷酸酯的最新进展。
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.004
Chen-Hui Mi, Xin-Ya Qi, Yan-Wen Ding, Jing Zhou, Jin-Wei Dao, Dai-Xu Wei

Infection and rejection in musculoskeletal trauma often pose challenges for natural healing, prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution. Polyhydroxyalkanoates (PHAs) are a large family of biopolyesters synthesised in microorganism, demonstrating excellent biocompatibility and controllable biodegradability for tissue remodelling and drug delivery. With different monomer-combination and polymer-types, multi-mechanical properties of PHAs making them have great application prospects in medical devices with stretching, compression, twist in long time, especially in musculoskeletal tissue engineering. This review systematically summarises the applications of PHAs in multiple tissues repair and drug release, encompassing areas such as bone, cartilage, joint, skin, tendons, ligament, cardiovascular tissue, and nervous tissue. It also discusses challenges encountered in their application, including high production costs, potential cytotoxicity, and uncontrollable particle size distribution. In conclusion, PHAs offer a compelling avenue for musculoskeletal system applications, striking a balance between biocompatibility and mechanical performance. However, addressing challenges in their production and application requires further research to unleash their full potential in tackling the complexities of musculoskeletal regeneration.

肌肉骨骼创伤中的感染和排异反应常常给自然愈合带来挑战,这促使人们探索生物仿生器官和组织移植作为一种常见的替代解决方案。聚羟基烷酸酯(PHA)是在微生物中合成的一大类生物聚酯,具有良好的生物相容性和可控的生物降解性,可用于组织重塑和药物输送。由于单体组合和聚合物类型不同,PHAs 具有多种机械特性,因此在长时间拉伸、压缩和扭曲的医疗设备中具有广阔的应用前景,尤其是在肌肉骨骼组织工程中。本综述系统总结了 PHAs 在多种组织修复和药物释放方面的应用,包括骨、软骨、关节、皮肤、肌腱、韧带、心血管组织和神经组织等领域。报告还讨论了在应用过程中遇到的挑战,包括生产成本高、潜在的细胞毒性和不可控的粒度分布。总之,PHA 为肌肉骨骼系统的应用提供了一个引人注目的途径,在生物相容性和机械性能之间取得了平衡。然而,要解决生产和应用中的难题,还需要进一步的研究,以充分发挥 PHAs 的潜力,解决肌肉骨骼再生的复杂问题。
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引用次数: 0
Early immunomodulation by magnesium ion: catalyst for superior osteogenesis. 镁离子的早期免疫调节作用:优质成骨的催化剂
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.009
Bo Li
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引用次数: 0
Organoid extracellular vesicle-based therapeutic strategies for bone therapy. 基于细胞外囊泡的有机体骨治疗策略。
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.002
Han Liu, Jiacan Su

With the rapid development of population ageing, bone-related diseases seriously affecting the life of the elderly. Over the past few years, organoids, cell clusters with specific functions and structures that are self-induced from stem cells after three-dimensional culture in vitro, have been widely used for bone therapy. Moreover, organoid extracellular vesicles (OEVs) have emerging as promising cell-free nanocarriers due to their vigoroso physiological effects, significant biological functions, stable loading capacity, and great biocompatibility. In this review, we first provide a comprehensive overview of biogenesis, internalisation, isolation, and characterisation of OEVs. We then comprehensively highlight the differences between OEVs and traditional EVs. Subsequently, we present the applications of natural OEVs in disease treatment. We also summarise the engineering modifications of OEVs, including engineering parental cells and engineering OEVs after isolation. Moreover, we provide an outlook on the potential of natural and engineered OEVs in bone-related diseases. Finally, we critically discuss the advantages and challenges of OEVs in the treatment of bone diseases. We believe that a comprehensive discussion of OEVs will provide more innovative and efficient solutions for complex bone diseases.

随着人口老龄化的快速发展,骨相关疾病严重影响着老年人的生活。在过去的几年里,由干细胞经过体外三维培养后自我诱导出的具有特定功能和结构的细胞簇--类器官(organoids)已被广泛用于骨治疗。此外,类器官胞外囊泡(OEVs)因其强大的生理效应、显著的生物学功能、稳定的负载能力和良好的生物相容性,已成为一种前景广阔的无细胞纳米载体。在这篇综述中,我们首先全面概述了 OEVs 的生物发生、内化、分离和表征。然后,我们全面强调了 OEV 与传统 EV 的区别。随后,我们介绍了天然 OEV 在疾病治疗中的应用。我们还总结了 OEV 的工程改造,包括亲代细胞工程和分离后的 OEV 工程。此外,我们还展望了天然 OEVs 和工程 OEVs 在骨相关疾病中的应用潜力。最后,我们批判性地讨论了 OEVs 在治疗骨病方面的优势和挑战。我们相信,对 OEVs 的全面探讨将为复杂的骨病提供更多创新、高效的解决方案。
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引用次数: 0
Fabrication of magnesium-doped porous polylactic acid microsphere for bone regeneration. 用于骨再生的掺镁多孔聚乳酸微球的制备。
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.007
Ziwei Tao, Ziyang Yuan, Dong Zhou, Lang Qin, Lan Xiao, Shihao Zhang, Changsheng Liu, Jinzhong Zhao, Yulin Li

Biodegradable polymer microspheres that can be used as drug carriers are of great importance in biomedical applications, however, there are still challenges in controllable preparation of microsphere surface morphology and improvement of bioactivity. In this paper, firstly, poly(L-lactic acid) (PLLA) was synthesised by ring-opening polymerisation under anhydrous anaerobic conditions and further combined with the emulsion method, biodegradable PLLA microspheres (PM) with sizes ranging from 60-100 μm and with good sphericity were prepared. In addition, to further improve the surface morphology of PLLA microspheres and enhance their bioactivity, functionalised porous PLLA microspheres loaded with magnesium oxide (MgO)/magnesium carbonate (MgCO3) (PMg) were also prepared by the emulsion method. The results showed that the loading of MgO/MgCO3 resulted in the formation of a porous structure on the surface of the microspheres (PMg) and the dissolved Mg2+ could be released slowly during the degradation of microspheres. In vitro cellular experiments demonstrated the good biocompatibility of PM and PMg, while the released Mg2+ further enhanced the anti-inflammatory effect and osteogenic activity of PMg. Functionalised PMg not only show promise for controlled preparation of drug carriers, but also have translational potential for bone regeneration.

可用作药物载体的生物降解聚合物微球在生物医学应用中具有重要意义,但在可控制备微球表面形态和提高生物活性方面仍存在挑战。本文首先在无水厌氧条件下采用开环聚合法合成了聚乳酸(PLLA),并进一步结合乳液法制备了可生物降解的聚乳酸微球(PM),其尺寸范围为 60-100 μm,且具有良好的球形度。此外,为了进一步改善聚乳酸微球的表面形态并提高其生物活性,还采用乳液法制备了负载氧化镁(MgO)/碳酸镁(MgCO3)的功能化多孔聚乳酸微球(PMg)。结果表明,MgO/MgCO3 的负载导致微球(PMg)表面形成多孔结构,溶解的 Mg2+ 可在微球降解过程中缓慢释放。体外细胞实验证明了 PM 和 PMg 具有良好的生物相容性,而释放的 Mg2+ 则进一步增强了 PMg 的抗炎效果和成骨活性。功能化 PMg 不仅有望用于药物载体的可控制备,还具有骨再生的转化潜力。
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引用次数: 0
AI accelerated discovery of self-assembling peptides. 人工智能加速了自组装肽的发现。
Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.12336/biomatertransl.2023.04.008
Yejiao Shi, Honggang Hu
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引用次数: 0
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Biomaterials Translational
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