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Chitosan-based injectable porous microcarriers with enhanced adipogenic differentiation and angiogenesis for subcutaneous adipose tissue regeneration 基于壳聚糖的可注射多孔微载体对皮下脂肪组织再生具有促进脂肪分化和血管生成的作用。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-03 DOI: 10.1016/j.bioadv.2025.214174
Yan Gan , Haotian Han , Ying Zhang , Ziwei Zhou , Xiang Shen , Jianjun Fang , Lei Cui , Zhihua Zhou
Chitosan is a promising biomaterial for tissue engineering, but its functionality is limited by a lack of bioactive sites. This study develops chitosan/amniotic membrane microcarriers to enhance vascularization and tissue regeneration for subcutaneous adipose tissue. The incorporation of decellularized amniotic membrane enhances the bioactivities of chitosan in promoting cell differentiation and angiogenesis. Optimized preparation yielded porous microcarriers with a particle size of 261.2 ± 28 μm and an average pore size of 19.0 ± 4 μm. In vitro degradation analysis showed accelerated degradation with higher amniotic membrane content. Cytocompatibility and adipogenic capacity assessments indicated that the microcarriers supported cell adhesion and proliferation over 7 days, with amniotic membrane facilitating adipogenic differentiation of adipose-derived stem cells. When injected subcutaneously into nude mice, these microcarriers formed neoplastic adipose tissues, which were harvested 8 weeks later. Fluorescence staining, oil-red O staining and CD31 labeling demonstrated that amniotic membrane incorporation significantly enhanced in vivo adipose tissue formation and angiogenesis.
壳聚糖是一种很有前途的组织工程生物材料,但由于缺乏生物活性位点,其功能受到限制。研究壳聚糖/羊膜微载体对皮下脂肪组织血管化和组织再生的促进作用。脱细胞羊膜的掺入增强了壳聚糖促进细胞分化和血管生成的生物活性。优化后制备的微载体粒径为261.2±28 μm,平均孔径为19.0±4 μm。体外降解分析表明,羊膜含量越高,降解速度越快。细胞相容性和成脂能力评估表明,微载体在7天内支持细胞粘附和增殖,羊膜促进脂肪源性干细胞的成脂分化。将这些微载体皮下注射到裸鼠体内,形成肿瘤脂肪组织,8周后采集。荧光染色、油红O染色和CD31标记显示,羊膜掺入显著增强了体内脂肪组织的形成和血管生成。
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引用次数: 0
Abdominal PP meshes coated with functional core-sheath biodegradable nanofibers with anticoagulant and antibacterial properties 具有抗凝血和抗菌性能的功能性芯鞘可生物降解纳米纤维包覆的腹部PP网。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-03 DOI: 10.1016/j.bioadv.2024.214163
Malo Dufay , Maude Jimenez , Mathilde Casetta , Feng Chai , Nicolas Blanchemain , Mickael Maton , Frédéric Cazaux , Séverine Bellayer , Stéphanie Degoutin
Abdominal hernia repair is a common surgical procedure, involving in most cases the use of textile meshes providing a mechanical barrier to consolidate the damaged surrounding tissues and prevent the resurgence of the hernia. However, in more than half cases postoperative complications such as adhesions and infections occur at the surface of the mesh, leading to chronic pain for the patient and requiring the removal of the implant. One of the most promising strategies to reduce the risk of postoperative adhesions and infections is to add a physical barrier between the mesh and the abdominal walls. In this study, we propose a strategy to develop functional hernia meshes possessing anticoagulant and antibacterial activities depending on the side of the implant. Two bioactive polymers were synthetized: a polysulfonate (poly(2-acrylamido-2-methylpropane sulfonic acid), PAMPS) one for anticoagulant activity and a polymer bearing ternary amines (poly((2-tert-butylamino) ethyl methacrylate), PTBAEMA) for antibacterial activity. These polymers were used to produce core-sheath nanofibers thanks to coaxial electrospinning with poly(ɛ-caprolactone) (PCL) as core and the bioactive polymer as sheath. The electrospinning parameters were optimized in order to obtain defect-free nanofibrous coatings onto the mesh with improved stability in water. The core-sheath structure was investigated as well as the presence of the functional groups at the surface. The in vitro cytocompatibility, anticoagulant activity and antibacterial activity were evaluated and highlighted the high potential of these coatings for the simultaneous prevention of postoperative adhesions and infections.
腹疝修补是一种常见的外科手术,在大多数情况下,使用纺织网提供机械屏障来巩固受损的周围组织,防止疝复发。然而,在超过一半的病例中,术后并发症如粘连和感染发生在补片表面,导致患者慢性疼痛并需要移除植入物。减少术后粘连和感染风险的最有希望的策略之一是在补片和腹壁之间添加物理屏障。在这项研究中,我们提出了一种开发具有抗凝血和抗菌活性的功能性疝补片的策略,这取决于植入物的侧面。合成了两种具有生物活性的聚合物:具有抗凝血活性的聚磺酸(聚(2-丙烯酰胺-2-甲基丙烷磺酸),PAMPS)和具有抗菌活性的三元胺(聚(2-叔丁基氨基)甲基丙烯酸乙酯,PTBAEMA)聚合物。以聚己内酯(PCL)为芯,生物活性聚合物为鞘,采用同轴静电纺丝技术制备了芯-鞘纳米纤维。通过对静电纺丝工艺参数的优化,得到了无缺陷的纳米纤维涂层,并提高了涂层在水中的稳定性。研究了核鞘结构以及表面官能团的存在。体外细胞相容性、抗凝血活性和抗菌活性进行了评估,并强调了这些涂层在同时预防术后粘连和感染方面的巨大潜力。
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引用次数: 0
E-jet printed polycaprolactone with strontium-substituted mesoporous bioactive glass nanoparticles for bone tissue engineering 以锶取代介孔生物活性玻璃纳米颗粒为材料的e -喷射打印聚己内酯骨组织工程研究。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-02 DOI: 10.1016/j.bioadv.2024.214173
Chee Hoe Kong , Chris Steffi , Yanli Cai , Wilson Wang
Osteoporosis, characterized by reduced bone mineral density and increased fracture risk, poses a significant health challenge, particularly for aging populations. Systemic treatments often lead to adverse side effects, emphasizing the need for localized solutions. This study introduces a 3D-printed polycaprolactone (PCL) scaffold embedded with strontium-substituted mesoporous bioactive glass nanoparticles (Sr-MBGNPs) and icariin (ICN) for the targeted regeneration of osteoporotic bone. The scaffold was characterized using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), ion release studies, and cellular assays, which confirmed its dual functionality in both enhancing osteoblast proliferation and differentiation and inhibiting osteoclastogenesis. The optimized Sr-MBGNP concentration ensured sustained ion release, superior hydrophilicity, and bioactivity without compromising scaffold integrity. Additionally, e-jet printing provided high precision and uniform pore sizes conducive to cellular activity. This novel scaffold platform demonstrates a promising localized treatment strategy, reducing systemic side effects while improving fixation stability. The innovative integration of Sr-MBGNPs and ICN highlights its potential to revolutionize osteoporosis therapy by promoting bone regeneration and mitigating bone resorption.
骨质疏松症以骨密度降低和骨折风险增加为特征,对健康构成重大挑战,特别是对老龄人口。全身治疗往往导致不良的副作用,强调需要局部解决。本研究介绍了一种3d打印聚己内酯(PCL)支架,内含锶取代的介孔生物活性玻璃纳米颗粒(Sr-MBGNPs)和淫羊藿苷(ICN),用于骨质疏松性骨的靶向再生。利用扫描电镜(SEM)、能谱(EDS)、离子释放研究和细胞分析对该支架进行了表征,证实了其促进成骨细胞增殖和分化以及抑制破骨细胞发生的双重功能。优化后的Sr-MBGNP浓度确保了离子的持续释放、优异的亲水性和生物活性,同时不影响支架的完整性。此外,电子喷射打印提供了高精度和均匀的孔径有利于细胞活性。这种新型支架平台展示了一种有前途的局部治疗策略,减少了全身副作用,同时提高了固定稳定性。Sr-MBGNPs和ICN的创新整合突出了其通过促进骨再生和减轻骨吸收来彻底改变骨质疏松症治疗的潜力。
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引用次数: 0
Biodegradable copper-containing mesoporous microspheres loaded with ginsenoside Rb1 for infarcted heart repair 可生物降解的含铜介孔微球装载人参皂苷Rb1用于心肌梗死修复。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-02 DOI: 10.1016/j.bioadv.2024.214172
Dongmin Chen , Xiaosheng Sheng , Huili Li , Qishu Jin , Ruqi Wang , Yuanzheng Qiu , Lefeng Su , Jinfeng Xu , Jiang Chang , Yumei Que , Chen Yang
The current unavailability of efficient myocardial repair therapies constitutes a significant bottleneck in the clinical management of myocardial infarction (MI). Ginsenoside Rb1 (GRb1) has emerged as a compound with potential benefits in safeguarding myocardial cells and facilitating the regeneration of myocardial tissue. However, its efficacy in treating MI-related ischemic conditions is hampered by its low bioavailability and inadequate angiogenic properties. In this study, the therapeutic potential of GRb1 is enhanced by a mesoporous basic copper carbonate (BCC) microsphere due to its excellent drug delivery capability and steady angiogenic degradation products (copper ions, Cu2+). The cell experiments revealed that GRb1 and Cu2+ could generate synergistic impacts on anti-cardiomyocyte apoptosis and endothelial cell angiogenesis, while a mouse model of MI illustrated that GRb1 loaded BCC (BCC@GRb1) could significantly enhance cardiac function, diminish the area of infarction and myocardial hypertrophy, reduce cardiomyocyte apoptosis, and augment vascularization within myocardial tissue. This investigation is pioneering in demonstrating the beneficial outcomes of combining drugs with bioactive carriers in myocardial regeneration and introduces a novel, precisely engineered drug delivery system as a potential therapeutic strategy for ischemic heart disease.
目前缺乏有效的心肌修复疗法是心肌梗死(MI)临床治疗的一个重要瓶颈。人参皂苷Rb1 (GRb1)是一种具有保护心肌细胞和促进心肌组织再生的潜在益处的化合物。然而,其治疗心肌梗死相关的缺血性疾病的有效性受到其低生物利用度和不充分的血管生成特性的阻碍。在本研究中,由于介孔碱式碳酸铜(BCC)微球具有优异的药物递送能力和稳定的血管生成降解产物(铜离子,Cu2+),因此增强了GRb1的治疗潜力。细胞实验显示,GRb1和Cu2+对抗心肌细胞凋亡和内皮细胞血管生成具有协同作用,而小鼠心肌梗死模型显示,GRb1负载BCC (BCC@GRb1)可显著增强心功能,缩小梗死面积和心肌肥厚,减少心肌细胞凋亡,增强心肌组织内血管化。这项研究开创性地证明了将药物与生物活性载体结合在心肌再生中的有益结果,并引入了一种新的、精确设计的药物输送系统,作为缺血性心脏病的潜在治疗策略。
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引用次数: 0
Biofunctionalisation of porous additively manufactured magnesium-based alloys for Orthopaedic applications: A review 多孔增材制造镁基合金在骨科应用中的生物功能化研究进展。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-02 DOI: 10.1016/j.bioadv.2024.214170
Tina Sadat Hashemi , Satish Jaiswal , Helen O. McCarthy , Tanya J. Levingstone , Nicholas J. Dunne
Magnesium (Mg) alloys have gained significant attention as a desirable choice of biodegradable implant for use in bone repair applications, largely owing to their unique material properties. More recently, Mg and Mg-based alloys have been used as load-bearing metallic scaffolds for bone tissue engineering applications, offering promising opportunities in the field. The mechanical properties and relative density of Mg-based alloys closely approximate those of natural human bone tissue, thereby mitigating the risk of stress-shielding effects. Furthermore, the inherent biodegradability of Mg-based alloys eliminates the necessity for a second surgical procedure for the removal of the implant, a frequent requirement with conventional non-degradable implants. However, a notable challenge remains in managing the high corrosion rate of Mg and Mg-based alloys within physiological environments to ensure that they meet the necessary functional requirements. Consequently, a comprehensive analysis and understanding of the corrosion behaviour of Mg and Mg-based alloys, coupled with optimisation of their surface properties, assume pivotal significance to ensure successful clinical application. The personalized 3D printing of Mg and Mg-based alloy implants represents a paradigm shift, offering a plethora of advantages, foremost among them being the enhancement of the bone healing process facilitated by the degradable porous structure conducive to bone ingrowth. Also, the emergence of surface functionalisation techniques for Mg-based implants amalgamates the mechanical and degradation properties inherent to metals with the enhanced biofunctionality offered by these coatings. This synergy presents a highly promising avenue for using Mg-based implants as temporary orthopaedic and dental solutions. This comprehensive review provides a detailed analysis of recent advancements encompassing alloying elements, additive manufacturing processes, lattice structures and biofunctionalised coatings to tailor the corrosion resistance, mechanical properties and biocompatibility of Mg-based orthopaedic implants.
镁合金由于其独特的材料特性,作为一种生物可降解的骨修复材料,受到了广泛的关注。最近,镁和镁基合金已被用作骨组织工程应用的承重金属支架,在该领域提供了很好的机会。镁基合金的力学性能和相对密度与天然人体骨组织非常接近,从而降低了应力屏蔽效应的风险。此外,镁基合金固有的生物可降解性消除了第二次手术移除植入物的必要性,而传统的不可降解植入物通常需要进行第二次手术。然而,一个值得注意的挑战仍然是如何在生理环境中控制镁和镁基合金的高腐蚀速率,以确保它们满足必要的功能要求。因此,全面分析和了解镁和镁基合金的腐蚀行为,并优化其表面性能,对确保成功的临床应用具有关键意义。Mg和Mg基合金植入物的个性化3D打印代表了一种范式转变,提供了大量的优势,其中最重要的是可降解的多孔结构促进了骨愈合过程,有利于骨向内生长。此外,镁基植入物表面功能化技术的出现将金属固有的机械和降解特性与这些涂层提供的增强的生物功能相结合。这种协同作用为使用镁基种植体作为临时矫形和牙科解决方案提供了一个非常有前途的途径。这篇全面的综述详细分析了合金元素、增材制造工艺、晶格结构和生物功能涂层的最新进展,以定制镁基骨科植入物的耐腐蚀性、机械性能和生物相容性。
{"title":"Biofunctionalisation of porous additively manufactured magnesium-based alloys for Orthopaedic applications: A review","authors":"Tina Sadat Hashemi ,&nbsp;Satish Jaiswal ,&nbsp;Helen O. McCarthy ,&nbsp;Tanya J. Levingstone ,&nbsp;Nicholas J. Dunne","doi":"10.1016/j.bioadv.2024.214170","DOIUrl":"10.1016/j.bioadv.2024.214170","url":null,"abstract":"<div><div>Magnesium (Mg) alloys have gained significant attention as a desirable choice of biodegradable implant for use in bone repair applications, largely owing to their unique material properties. More recently, Mg and Mg-based alloys have been used as load-bearing metallic scaffolds for bone tissue engineering applications, offering promising opportunities in the field. The mechanical properties and relative density of Mg-based alloys closely approximate those of natural human bone tissue, thereby mitigating the risk of stress-shielding effects. Furthermore, the inherent biodegradability of Mg-based alloys eliminates the necessity for a second surgical procedure for the removal of the implant, a frequent requirement with conventional non-degradable implants. However, a notable challenge remains in managing the high corrosion rate of Mg and Mg-based alloys within physiological environments to ensure that they meet the necessary functional requirements. Consequently, a comprehensive analysis and understanding of the corrosion behaviour of Mg and Mg-based alloys, coupled with optimisation of their surface properties, assume pivotal significance to ensure successful clinical application. The personalized 3D printing of Mg and Mg-based alloy implants represents a paradigm shift, offering a plethora of advantages, foremost among them being the enhancement of the bone healing process facilitated by the degradable porous structure conducive to bone ingrowth. Also, the emergence of surface functionalisation techniques for Mg-based implants amalgamates the mechanical and degradation properties inherent to metals with the enhanced biofunctionality offered by these coatings. This synergy presents a highly promising avenue for using Mg-based implants as temporary orthopaedic and dental solutions. This comprehensive review provides a detailed analysis of recent advancements encompassing alloying elements, additive manufacturing processes, lattice structures and biofunctionalised coatings to tailor the corrosion resistance, mechanical properties and biocompatibility of Mg-based orthopaedic implants.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"169 ","pages":"Article 214170"},"PeriodicalIF":5.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bone regeneration in sheep model induced by strontium-containing mesoporous bioactive glasses 含锶介孔生物活性玻璃诱导羊骨再生模型的研究。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-12-30 DOI: 10.1016/j.bioadv.2024.214168
Javier Jiménez-Holguín , Daniel Lozano , Melchor Saiz-Pardo , David de Pablo , Luis Ortega , Silvia Enciso , Blanca Fernández-Tomé , Idoia Díaz-Güemes , Francisco Miguel Sánchez-Margallo , María Teresa Portolés , Daniel Arcos
Local delivery of therapeutic ions from bioactive mesoporous glasses (MBGs) is postulated as one of the most promising strategies for regenerative therapy of critical bone defects. Among these ions, Sr2+ cation has been widely considered for this purpose as part of the composition of MBGs. MBGs of chemical composition 75SiO2-25-x CaO-5P2O5-xSrO with x = 0, 2.5 and 5 (% mol) were prepared by the evaporation induced self-assembly (EISA) method. Strontium incorporation did not affect the apatite forming ability of Sr-free MBG when these bioceramics are treated with simulated body fluid (SBF). In vitro cell viability showed that proliferation of MC3T3-E1 preosteoblast is not affected by the presence of Sr2+ cations, whereas ALP activity and gene expression of Runx2, ALP and VEGF is increased as a function of Sr content. Besides, cell proliferation and VEGF expression of HUVEC cells were also increased with the Sr2+ content. In this work, we present for the first time the effects of Sr containing MBGs on bone regeneration in a large animal model (sheep), after implantation in a cavitary defect. The histomorphometrical analysis and immunohistochemistry indicate that the incorporation of Sr2+ ion greatly enhances the osteoregenerating potential of MBGs. In this sense, the measured ossification areas were 7 % and 20 % for MBG and Sr-MBG, respectively. Besides, the thickness of the newly formed trabeculae was 15 μm and 30 μm for MBG and Sr-MBG, respectively. This enhancement of Sr2+ mediated bone formation would be justified by the transient osteoclastogenesis inhibition and the osteogenesis-angiogenesis increase due to the endothelial cell proliferation and increased vascular endothelial growth factor expression.
生物活性介孔玻璃(MBGs)局部递送治疗离子被认为是最具前景的骨缺损再生治疗策略之一。在这些离子中,Sr2+阳离子被广泛认为是MBGs组成的一部分。采用蒸发诱导自组装(EISA)法制备了化学成分为75SiO2-25-x CaO-5P2O5-xSrO的MBGs,分别为x = 0、2.5和5 (% mol)。当这些生物陶瓷用模拟体液(SBF)处理时,锶掺入不影响无锶MBG的磷灰石形成能力。体外细胞活力实验表明,Sr2+的存在不影响MC3T3-E1成骨前细胞的增殖,而ALP活性和Runx2、ALP和VEGF的基因表达随Sr含量的增加而增加。此外,随着Sr2+含量的增加,HUVEC细胞的增殖和VEGF的表达也增加。在这项工作中,我们首次在大型动物模型(羊)中展示了含Sr的MBGs在骨缺损植入后对骨再生的影响。组织形态学分析和免疫组织化学分析表明,Sr2+离子的掺入大大增强了MBGs的成骨潜能。从这个意义上说,MBG和Sr-MBG测量的骨化面积分别为7%和20%。MBG和Sr-MBG新形成的小梁厚度分别为15 μm和30 μm。Sr2+介导的骨形成的增强可以通过短暂的破骨细胞生成抑制和内皮细胞增殖和血管内皮生长因子表达增加导致的骨生成-血管生成增加来证明。
{"title":"Bone regeneration in sheep model induced by strontium-containing mesoporous bioactive glasses","authors":"Javier Jiménez-Holguín ,&nbsp;Daniel Lozano ,&nbsp;Melchor Saiz-Pardo ,&nbsp;David de Pablo ,&nbsp;Luis Ortega ,&nbsp;Silvia Enciso ,&nbsp;Blanca Fernández-Tomé ,&nbsp;Idoia Díaz-Güemes ,&nbsp;Francisco Miguel Sánchez-Margallo ,&nbsp;María Teresa Portolés ,&nbsp;Daniel Arcos","doi":"10.1016/j.bioadv.2024.214168","DOIUrl":"10.1016/j.bioadv.2024.214168","url":null,"abstract":"<div><div>Local delivery of therapeutic ions from bioactive mesoporous glasses (MBGs) is postulated as one of the most promising strategies for regenerative therapy of critical bone defects. Among these ions, Sr<sup>2+</sup> cation has been widely considered for this purpose as part of the composition of MBGs. MBGs of chemical composition 75SiO<sub>2</sub>-25-x CaO-5P<sub>2</sub>O<sub>5</sub>-xSrO with x = 0, 2.5 and 5 (% mol) were prepared by the evaporation induced self-assembly (EISA) method. Strontium incorporation did not affect the apatite forming ability of Sr-free MBG when these bioceramics are treated with simulated body fluid (SBF). <em>In vitro</em> cell viability showed that proliferation of MC3T3-E1 preosteoblast is not affected by the presence of Sr<sup>2+</sup> cations, whereas ALP activity and gene expression of Runx2, ALP and VEGF is increased as a function of Sr content. Besides, cell proliferation and VEGF expression of HUVEC cells were also increased with the Sr<sup>2+</sup> content. In this work, we present for the first time the effects of Sr containing MBGs on bone regeneration in a large animal model (sheep), after implantation in a cavitary defect. The histomorphometrical analysis and immunohistochemistry indicate that the incorporation of Sr<sup>2+</sup> ion greatly enhances the osteoregenerating potential of MBGs. In this sense, the measured ossification areas were 7 % and 20 % for MBG and Sr-MBG, respectively. Besides, the thickness of the newly formed trabeculae was 15 μm and 30 μm for MBG and Sr-MBG, respectively. This enhancement of Sr<sup>2+</sup> mediated bone formation would be justified by the transient osteoclastogenesis inhibition and the osteogenesis-angiogenesis increase due to the endothelial cell proliferation and increased vascular endothelial growth factor expression.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"169 ","pages":"Article 214168"},"PeriodicalIF":5.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Magnetic field-oriented conductive decellularized extracellular matrix hydrogel synergizes with electrical stimulation to promote spinal cord injury repair and electrophysiological function restoration 磁场定向导电脱细胞细胞外基质水凝胶与电刺激协同促进脊髓损伤修复和电生理功能恢复。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-12-30 DOI: 10.1016/j.bioadv.2024.214169
Ruijia Yan , Shu Chen , Bixue Wang, Changsheng Liu, Xi Chen
Spinal cord injury (SCI) results in electrophysiological and behavioral dysfunction. Electrical stimulation (ES) is considered to be an effective treatment for mild SCI; however, ES is not applicable to severe SCI due to the disruption of electrical conduction caused by tissue defects. Therefore, the use of conductive materials to fill the defects and restore electrical conduction in the spinal cord is a promising therapeutic strategy. In this study, we used ultrasound to composite conductive reduced graphene oxide (rGO) and magnetic Fe3O4 nanoparticles and encapsulated them into gelatin methacryloyl (GelMA) along with decellularized extracellular matrix (dECM) to form a conductive composite hydrogel, rGO/Fe3O4/dECM@GelMA. The rGO/Fe3O4 complexes were able to orientate themselves in the hydrogel with a magnetic field, conferring an orientated electrical conduction function to the hydrogel. The implantation of this composite hydrogel re-established the electrical conduction in the damaged spinal cord and synergized with ES to promote the regeneration of neurons and myelinated axons at the injury site, resulting in the restoration of electrophysiological function of the spinal cord and motor function of the hind limbs of mice. Our study combines a conductive tissue-engineered scaffold with ES therapy to improve the efficacy of ES in severe spinal cord injuries and promote the restoration of spinal cord function.
脊髓损伤导致电生理和行为功能障碍。电刺激(ES)被认为是治疗轻度脊髓损伤的有效方法;然而,由于组织缺陷导致的电传导中断,ES不适用于严重的SCI。因此,利用导电材料填充缺损,恢复脊髓的电传导是一种很有前景的治疗策略。在这项研究中,我们使用超声波将导电还原氧化石墨烯(rGO)和磁性Fe3O4纳米颗粒复合,并将其与脱细胞细胞外基质(dECM)一起包裹在明胶甲基丙烯酰(GelMA)中,形成导电复合水凝胶rGO/Fe3O4/dECM@GelMA。rGO/Fe3O4配合物能够在磁场作用下在水凝胶中定向,赋予水凝胶定向导电功能。该复合水凝胶的植入重建了受损脊髓的电传导,并与ES协同促进损伤部位神经元和髓鞘轴突的再生,使小鼠脊髓电生理功能和后肢运动功能得到恢复。我们的研究将导电组织工程支架与ES治疗相结合,以提高ES治疗严重脊髓损伤的疗效,促进脊髓功能的恢复。
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引用次数: 0
A mini-invasive injectable hydrogel for temporomandibular joint osteoarthritis: Its pleiotropic effects and multiple pathways in cartilage regeneration 一种用于颞下颌关节骨性关节炎的微创注射水凝胶:其软骨再生的多效性和多途径。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-12-29 DOI: 10.1016/j.bioadv.2024.214162
Xiao Xu , Jiao Sun
There are two bottlenecks in the treatment of TMJOA (temporomandibular joint osteoarthritis): ① lacking of easy-to-use repairing materials for damaged condylar cartilage; ② local inflammation interfering with in situ regeneration. In response to them, we constructed a biomimetic tilapia type I gelatin/hyaluronic acid (TGI/HA) hydrogel in this paper. It was endowed with the capability to immunoregulate mircoenvironment and concurrently induce regeneration in multiple ways. It not only reduced excretion of ECM-degrading enzymes and inflammatory factors, therefore reversing local inflammation, but also created microenvironment conducive to reparation by acting upon macrophages and T cells. In in vivo experiments, the TGI/HA hydrogel effectively restored the damaged cartilage on rat condyle, suggesting it had potential in clinical application.
颞下颌关节骨性关节炎(TMJOA)的治疗存在两个瓶颈:①缺乏易于使用的髁突软骨损伤修复材料;②局部炎症干扰原位再生。为此,我们构建了一种仿生罗非鱼I型明胶/透明质酸(TGI/HA)水凝胶。它具有免疫调节微环境和多种方式诱导再生的能力。它不仅减少ecm降解酶和炎症因子的排泄,从而逆转局部炎症,而且通过作用于巨噬细胞和T细胞创造有利于修复的微环境。在体内实验中,TGI/HA水凝胶能有效修复大鼠髁上受损软骨,具有临床应用潜力。
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引用次数: 0
Effect of molecular weight of tyramine-modified hyaluronan on polarization state of THP-1 and peripheral blood mononuclear cells-derived macrophages 酪胺修饰透明质酸分子量对THP-1和外周血单核细胞源性巨噬细胞极化状态的影响。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-12-29 DOI: 10.1016/j.bioadv.2024.214166
Jacek K. Wychowaniec , Ezgi Irem Bektas , Andrea J. Vernengo , Marcia Muerner , Marielle Airoldi , Paul Sean Tipay , Jiranuwat Sapudom , Jeremy Teo , David Eglin , Matteo D'Este
The immunomodulatory properties of hyaluronan and its derivatives are key to their use in medicine and tissue engineering. In this work we evaluated the capability of soluble tyramine-modified hyaluronan (THA) synthesized from hyaluronan of two molecular weights (low Mw = 280 kDa and high Mw = 1640 kDa) for polarization of THP-1 and peripheral blood mononuclear cells (PBMCs)-derived macrophages (MΦs). We demonstrate the polarization effects of the supplemented THA by flow cytometry and bead-based multiplex immunoassay for the THP-1 derived MΦs and by semi-automated image analysis from confocal microscopy, immunofluorescent staining utilizing CD68 and CD206 surface markers, RT-qPCR gene expression analysis, as well as using the enzyme-linked immunosorbent assay (ELISA) for PBMCs-derived MΦs. Our data indicate that supplementation with LMW THA drives changes in THP-1 derived MΦs towards a pro-inflammatory M1-like phenotype, whereas supplementation with the HMW THA leads to a more mixed profile with some features of both M1 and M2 phenotypes, suggesting either a heterogeneous population or a transitional state. For cells directly sourced from human patients, PMBCs-derived MΦs, results exhibit a higher degree of variability, pointing out a differential regulation of factors including IL-10 and CD206 between the two cell sources. While human primary cells add to the clinical relevance, donor diversity introduces wider variability in the dataset, preventing drawing strong conclusions. Nevertheless, the MΦs profiles observed in THP-1 derived cells for treatments with LMW and HMW THA are generally consistent with what might be expected for the treatment with non-modified hyaluronans of respective molecular weights, confirming the known association holds true for the chemically tyramine-modified hyaluronan. We stipulate that these responses will provide basis for more accurate in vivo representation and translational immunomodulatory guidance for the use of THA-based biomaterials to a wider biomaterials and tissue engineering communities.
透明质酸及其衍生物的免疫调节特性是其在医学和组织工程中应用的关键。在这项工作中,我们评估了由两种分子量的透明质酸(低Mw = 280 kDa和高Mw = 1640 kDa)合成的可溶性酪胺修饰透明质酸(THA)对THP-1和外周血单核细胞(PBMCs)来源的巨噬细胞极化的能力(MΦs)。我们通过流式细胞术和基于微球的多重免疫分析法对THP-1衍生物MΦs、共聚焦显微镜的半自动图像分析、利用CD68和CD206表面标记物的免疫荧光染色、RT-qPCR基因表达分析以及酶联免疫吸附法(ELISA)对pbmcs衍生物MΦs证明了补充THA的极化效应。我们的数据表明,补充LMW THA会导致THP-1衍生的MΦs向着促炎性M1样表型变化,而补充HMW THA会导致更混合的特征,具有M1和M2表型的一些特征,这表明要么是异质群体,要么是过渡状态。对于直接来源于人类患者的细胞,pmbc衍生的MΦs,结果显示出更高程度的可变性,指出两种细胞来源之间IL-10和CD206等因子的差异调节。虽然人类原代细胞增加了临床相关性,但供体多样性在数据集中引入了更大的可变性,从而无法得出强有力的结论。然而,在THP-1衍生细胞中观察到的MΦs谱图与LMW和HMW THA处理的结果大致一致,这证实了已知的关联对于化学酪胺修饰的透明质酸是正确的。我们认为这些反应将为更准确的体内表征和翻译免疫调节指导提供基础,为更广泛的生物材料和组织工程领域使用基于tha的生物材料提供指导。
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引用次数: 0
Collagen/polyvinyl alcohol scaffolds combined with platelet-rich plasma to enhance anterior cruciate ligament repair 胶原/聚乙烯醇支架联合富血小板血浆增强前交叉韧带修复。
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-12-29 DOI: 10.1016/j.bioadv.2024.214164
Xiaohan Sun , Nanxin Zhang , Longhui Chen , Yuchao Lai , Shasha Yang , Qiang Li , Yunquan Zheng , Li Chen , Xianai Shi , Jianmin Yang
In anterior cruciate ligament (ACL) repair methods, the continuous enzymatic erosion of synovial fluid can impede healing and potentially lead to repair failure, as well as exacerbate articular cartilage wear, resulting in joint degeneration. Inspired by the blood clot during medial collateral ligament healing, we developed a composite scaffold comprising collagen (1 %, w/v) and polyvinyl alcohol (5 %, w/v) combined with platelet-rich plasma (PRP). The composite scaffold provides a protective barrier against synovial erosion for the ruptured ACL, while simultaneously facilitating tissue repair, thereby enhancing the efficacy of ACL repair techniques. The composite scaffold is primarily formed through hydrogen bonding between molecular chains and physical cross-linking of microcrystalline regions using a simple cyclic freeze-thaw method, resulting in improved mechanical properties and an extended degradation period. The maximum tensile fracture load of the composite scaffold reached 5.99 ± 0.30 N. The incorporation of PRP facilitates cell migration, proliferation, and blood vessel growth by enabling slow release of various growth factors. In vivo results demonstrate that this composite scaffold promotes rabbit hindlimb rupture ACL healing by stimulating fibroblast proliferation, collagen deposition, microvascular formation, and proprioceptor generation. Furthermore, it effectively reduces meniscus and cartilage wear while mitigating bone arthritis and joint degenerative diseases. Overall, our proposed composite scaffold holds great promise as a candidate for ACL healing.
在前交叉韧带(ACL)修复方法中,滑液的持续酶侵蚀会阻碍愈合并可能导致修复失败,并加剧关节软骨磨损,导致关节退变。受内侧副韧带愈合过程中的血凝块的启发,我们开发了一种由胶原蛋白(1%,w/v)和聚乙烯醇(5%,w/v)结合富血小板血浆(PRP)组成的复合支架。复合支架为断裂的前交叉韧带提供防止滑膜侵蚀的保护屏障,同时促进组织修复,从而提高前交叉韧带修复技术的疗效。复合支架主要采用简单的循环冻融法,通过分子链之间的氢键和微晶区域的物理交联形成,从而提高了材料的力学性能,延长了降解期。复合支架的最大拉伸断裂载荷达到5.99±0.30 n, PRP的掺入使多种生长因子缓释,促进细胞迁移、增殖和血管生长。体内实验结果表明,该复合支架通过刺激成纤维细胞增殖、胶原沉积、微血管形成和本体受体生成,促进兔后肢断裂前交叉韧带愈合。此外,它有效地减少半月板和软骨磨损,同时减轻骨关节炎和关节退行性疾病。总的来说,我们提出的复合支架作为前交叉韧带愈合的候选材料具有很大的前景。
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Materials Science & Engineering C-Materials for Biological Applications
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