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An induced pluripotent stem cell-based approach for hair follicle development and regeneration 基于诱导多能干细胞的毛囊发育和再生方法
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.07.005
Poornima Sivamani , Ramya Lakshmi Rajendran , Prakash Gangadaran , Byeong-Cheol Ahn

Because hair loss is a common concern for many individuals, potential regenerative therapies of hair follicles have been extensively researched. Induced pluripotent stem cells (iPSCs) are a promising avenue for hair follicle regeneration. This review explores current iPSC-based approaches and highlights their potential applications and challenges in hair restoration. The principles of iPSC technology, iPSC differentiation into hair follicle precursor cells, and potential clinical implications for hair follicle regeneration are also discussed. This overview of iPSCs and their applications aims to contribute to our understanding of their role in hair restoration and potential future therapeutic applications.

由于脱发是许多人共同关心的问题,人们对毛囊再生疗法的潜力进行了广泛研究。诱导多能干细胞(iPSC)是毛囊再生的一个很有前景的途径。这篇综述探讨了目前基于 iPSC 的方法,并重点介绍了它们在毛发修复中的潜在应用和挑战。文中还讨论了 iPSC 技术的原理、iPSC 向毛囊前体细胞的分化以及对毛囊再生的潜在临床意义。这篇关于 iPSC 及其应用的综述旨在帮助我们了解 iPSC 在毛发修复中的作用以及未来潜在的治疗应用。
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引用次数: 0
Evaluation of decellularized caprine small intestine submucosa encapsulated with nano-formulations of cerium oxide and curcumin in the management of burn wound 评估用氧化铈和姜黄素纳米制剂包裹的脱细胞黄羊小肠黏膜在烧伤创面治疗中的效果
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.08.002
Juan Li, Hao Li, Kaikai Wang, Haiyan Chou

The management of burn injuries presents a significant challenge in clinical settings, yet an optimal solution remains elusive. Therefore, this study aimed to develop a topical therapeutic formulation to address the complex issues hindering burn wound healing. Emphasizing the sustained presence of bioactive principles, we synthesized a bioactive gel derived from decellularized caprine small intestine submucosa (D-CIS) and encapsulated it with nano-formulations of cerium oxide and curcumin to create a burn wound dressing material with enhanced properties. The choice of encapsulated components was guided by their antimicrobial, antioxidant, and immune-modulating characteristics, along with their inherent ability to gradually release bioactive substances. The encapsulated (cerium oxide and curcumin) D-CIS bioactive gel demonstrated a range of properties, including antimicrobial, antioxidant, and anti-inflammatory effects, along with sustained release kinetics of bioactive molecules. These combined effects facilitated accelerated burn wound healing by mitigating oxidative stress, reducing inflammation, and promoting cell recruitment for epithelial and vascular regeneration. This study contributes to the development of a novel bioactive gel incorporating cerium oxide and curcumin, offering a promising approach to enhance burn wound healing.

烧伤的处理是临床环境中的一项重大挑战,但最佳解决方案仍未出现。因此,本研究旨在开发一种局部治疗配方,以解决阻碍烧伤伤口愈合的复杂问题。我们强调生物活性原理的持续存在,从脱细胞毛细小肠粘膜下层(D-CIS)中合成了一种生物活性凝胶,并将其与氧化铈和姜黄素的纳米配方封装在一起,制成了一种性能更强的烧伤创面敷料材料。封装成分的选择取决于其抗菌、抗氧化和免疫调节特性,以及逐渐释放生物活性物质的固有能力。封装的(氧化铈和姜黄素)D-CIS 生物活性凝胶显示出一系列特性,包括抗菌、抗氧化和抗炎作用,以及生物活性分子的持续释放动力学。这些综合效应通过减轻氧化应激、减少炎症和促进细胞募集以促进上皮和血管再生,加快了烧伤创面的愈合。这项研究有助于开发一种融合了氧化铈和姜黄素的新型生物活性凝胶,为促进烧伤伤口愈合提供了一种前景广阔的方法。
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引用次数: 0
Dendrobium officinale polysaccharide promotes angiogenesis as well as follicle regeneration and hair growth through activation of the WNT signaling pathway 铁皮石斛多糖通过激活 WNT 信号通路促进血管生成以及毛囊再生和毛发生长
IF 4.3 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.04.014
Yujin Zhang , Qing Tang , Bijun Zeng , Fengjiao Wang , Meijunzi Luo , Pan Huang , Ling Chen , Haizhen Wang

Introduction

Hair loss is one of the common clinical conditions in modern society. Although it is not a serious disease that threatens human life, it brings great mental stress and psychological burden to patients. This study investigated the role of dendrobium officinale polysaccharide (DOP) in hair follicle regeneration and hair growth and its related mechanisms.

Methods

After in vitro culture of mouse antennal hair follicles and mouse dermal papilla cells (DPCs), and mouse vascular endothelial cells (MVECs), the effects of DOP upon hair follicles and cells were evaluated using multiple methods. DOP effects were evaluated by measuring tentacle growth, HE staining, immunofluorescence, Western blot, CCK-8, ALP staining, tube formation, scratch test, and Transwell. LDH levels, WNT signaling proteins, and therapeutic mechanisms were also analyzed.

Results

DOP promoted tentacle hair follicle and DPCs growth in mice and the angiogenic, migratory and invasive capacities of MVECs. Meanwhile, DOP was also capable of enhancing angiogenesis and proliferation-related protein expression. Mechanistically, DOP activated the WNT signaling and promoted the expression level of β-catenin, a pivotal protein of the pathway, and the pathway target proteins Cyclin D1, C-Myc, and LDH activity. The promotional effects of DOP on the biological functions of DPCs and MVECs could be effectively reversed by the WNT signaling pathway inhibitor IWR-1.

Conclusion

DOP advances hair follicle and hair growth via the activation of the WNT signaling. This finding provides a mechanistic reference and theoretical basis for the clinical use of DOP in treating hair loss.

导言脱发是现代社会常见的临床病症之一。虽然它不是威胁人类生命的严重疾病,但却给患者带来了巨大的精神压力和心理负担。方法体外培养小鼠触角毛囊、小鼠真皮乳头细胞(DPCs)和小鼠血管内皮细胞(MVECs)后,采用多种方法评价 DOP 对毛囊和细胞的作用。通过测量触角生长、HE 染色、免疫荧光、Western 印迹、CCK-8、ALP 染色、管形成、划痕试验和 Transwell 来评估 DOP 的影响。结果 DOP 能促进小鼠触手毛囊和 DPCs 的生长,以及 MVECs 的血管生成、迁移和侵袭能力。同时,DOP 还能增强血管生成和增殖相关蛋白的表达。从机理上讲,DOP能激活WNT信号转导,促进该通路的关键蛋白β-catenin的表达水平,以及该通路靶蛋白Cyclin D1、C-Myc和LDH的活性。DOP对DPCs和MVECs生物功能的促进作用可被WNT信号通路抑制剂IWR-1有效逆转。这一发现为临床使用 DOP 治疗脱发提供了机理参考和理论依据。
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引用次数: 0
Evaluation of the effect of co-transplantation of collagen-hydroxyapatite bio-scaffold containing nanolycopene and human endometrial mesenchymal stem cell derived exosomes to regenerate bone in rat critical size calvarial defect 含纳米多烯烃的胶原-羟基磷灰石生物支架与人子宫内膜间充质干细胞衍生的外泌体共同移植对大鼠临界尺寸腓骨缺损骨再生效果的评估
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.02.006
Masoumeh Einabadi , Azadeh Izadyari Aghmiuni , Laleh Foroutani , Arman Ai , Mojdeh Salehi Namini , Ali Farzin , Amir Nahanmoghadam , Sadegh Shirian , Hossein Kargar Jahromi , Jafar Ai

This study aimed to evaluate the effect of nanoparticles based on the PLGA and biomolecule of lycopene (i.e. NLcp) and exosomes loaded on hydroxyapatite/collagen-based scaffolds (HA/Coll), on human endometrial MSCs (hEnMSCs) differentiation into osteoblast cells. To this end, after synthesizing NLcp and isolating hEnMSC-derived exosomes, and studying their characterizations, HA/Coll scaffold with/without NLcp and exosome was fabricated. In following, the rat skull-defect model was created on 54 male Sprague–Dawley rats (12 weeks old) which were classified into 6 groups [control group (4 healthy rats), negative control group: bone defect without grafting (10 rats), and experimental groups including bone defect grafted with HA/Coll scaffold (10 rats), HA/Coll/NLcp scaffold (10 rats), HA/Coll scaffold + exosome (10 rats), and HA/Coll-NLcp scaffold + exosome (10 rats)]. Finally, the grafted membrane along with its surrounding tissues was removed at 90 days after surgery, to assess the amount of defect repair by Hematoxylin and eosin staining. Moreover, immunohistochemical and X-ray Micro-Computed Tomography (Micro-CT) analyses were performed to assess osteocalcin and mean bone volume fraction (BVF). Based on the results, although, the existence of the exosome in the scaffold network can significantly increase mean BVF compared to HA/Coll scaffold and HA/Coll-NLcp scaffold (2.25-fold and 1.5-fold, respectively). However, the combination of NLcp and exosome indicated more effect on mean BVF; so that the HA/Coll-NLcp scaffold + exosome led to a 15.95 % increase in mean BVF than the HA/Coll scaffold + exosome. Hence, synthesized NLcp in this study can act as a suitable bioactive to stimulate the osteogenic, promotion of cell proliferation and its differentiation when used in the polymer scaffold structure or loaded into polymeric carriers containing the exosome.

本研究旨在评估负载在羟基磷灰石/胶原基支架(HA/Coll)上的基于PLGA和番茄红素生物大分子的纳米颗粒(即NLcp)和外泌体对人子宫内膜间充质干细胞(hEnMSCs)分化成成骨细胞的影响。为此,在合成 NLcp 和分离 hEnMSC 衍生的外泌体并研究其特性后,制备了含有/不含有 NLcp 和外泌体的 HA/Coll 支架。随后,以 54 只雄性 Sprague-Dawley 大鼠(12 周大)为对象建立了大鼠颅骨缺损模型,并将其分为 6 组[对照组(4 只健康大鼠)、阴性对照组(10 只健康大鼠)、未植骨的骨缺损组(10 只健康大鼠)]:实验组包括骨缺损移植 HA/Coll 支架(10 只大鼠)、HA/Coll/NLcp 支架(10 只大鼠)、HA/Coll 支架 + 外泌体(10 只大鼠)和 HA/Coll-NLcp 支架 + 外泌体(10 只大鼠)]。最后,在术后 90 天取出移植膜及其周围组织,用苏木精和伊红染色法评估缺损修复的程度。此外,还进行了免疫组化和 X 射线显微计算机断层扫描(Micro-CT)分析,以评估骨钙素和平均骨体积分数(BVF)。结果表明,虽然与 HA/Coll 支架和 HA/Coll-NLcp 支架相比(分别为 2.25 倍和 1.5 倍),外泌体在支架网络中的存在能显著提高平均骨体积分数。然而,NLcp 和外泌体的组合对平均血流变异系数的影响更大;因此,HA/Coll-NLcp 支架+外泌体比 HA/Coll 支架+外泌体使平均血流变异系数增加了 15.95%。因此,本研究中合成的 NLcp 在聚合物支架结构中使用或装入含有外泌体的聚合物载体中时,可作为一种合适的生物活性物质来刺激成骨、促进细胞增殖及其分化。
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引用次数: 0
Enhancement of tracheal cartilage regeneration by local controlled release of stromal cell-derived factor 1α with gelatin hydrogels and systemic administration of high-mobility group box 1 peptide 通过明胶水凝胶局部控释基质细胞衍生因子 1α 和全身给药高迁移率基团框 1 肽促进气管软骨再生
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.06.017
Kumiko (Ogi) Suzuki , Tatsuya Okamoto , Katsuto Tamai , Yasuhiko Tabata , Etsuro Hatano

Introduction

This present study evaluated the effect of combination therapy with stromal cell-derived factor 1α (SDF-1α) and high-mobility group box 1 (HMGB1) peptide on the regeneration of tracheal injury in a rat model.

Methods

To improve this effect, SDF-1α was incorporated into a gelatin hydrogel, which was then applied to the damaged tracheal cartilage of rats for local release. Furthermore, HMGB1 peptide was repeatedly administered intravenously. Regeneration of damaged tracheal cartilage was evaluated in terms of cell recruitment.

Results

Mesenchymal stem cells (MSC) with C-X-C motif chemokine receptor 4 (CXCR4) were mobilized more into the injured area, and consequently the fastest tracheal cartilage regeneration was observed in the combination therapy group eight weeks after injury.

Conclusions

The present study demonstrated that combination therapy with gelatin hydrogel incorporating SDF-1α and HMGB1 peptide injected intravenously can enhance the recruitment of CXCR4-positive MSC, promoting the regeneration of damaged tracheal cartilage.

引言 本研究评估了基质细胞衍生因子 1α(SDF-1α)和高迁移率基团框 1(HMGB1)肽联合疗法对大鼠气管损伤再生的影响。方法 为了提高疗效,将 SDF-1α 加入明胶水凝胶中,然后将其涂在大鼠受损的气管软骨上进行局部释放。此外,还反复静脉注射 HMGB1 肽。结果具有 C-X-C motif趋化因子受体 4(CXCR4)的间充质干细胞(MSC)被更多地动员到损伤区域,因此在损伤八周后,联合疗法组的气管软骨再生速度最快。结论 本研究表明,静脉注射含有SDF-1α和HMGB1肽的明胶水凝胶联合疗法可增强CXCR4阳性间充质干细胞的募集,促进受损气管软骨的再生。
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引用次数: 0
Effect of leukocyte and platelet-rich plasma on osseointegration after implant placement in mouse maxilla 白细胞和富血小板血浆对小鼠上颌骨植入种植体后骨结合的影响
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.08.019
Mauricio Zapata-Sifuentes , Angela Quispe-Salcedo , Taisuke Watanabe , Tomoyuki Kawase , Hayato Ohshima

Introduction

Osseointegration, the direct contact between an implant and bone, can be achieved by direct and/or indirect osteogenesis. Platelet-rich plasma accelerates tissue regeneration, wound healing, and osseointegration. This study aimed to analyze the effects of leukocyte and platelet-rich plasma (L-PRP) on direct and indirect osteogenesis after implant placement in a mouse maxilla.

Methods

Blood was collected from the tail vein of 4–8-week-old male ICR mice and L-PRP was obtained after double-spin cycle centrifugation. After the right upper first molars of 4-week-old ICR mice were extracted while under deep anesthesia, the alveolar sockets were prepared with a drill, and titanium implants blasted with hydroxyapatite/β-tricalcium phosphate were placed into the cavity filled with 1.5 μL of L-PRP. Samples were collected from the animals 3–28 days after implantation, and immunohistochemistry for osteopontin, Ki67 (cell proliferation marker), cathepsin-K (osteoclast marker), and osteonectin (osteoblast marker) was performed.

Results

Cell proliferation was significantly higher in the L-PRP group than in the control group on postoperative days 3 and 5. The activities of osteoclast-lineage cells and osteoblasts increased significantly on day 5 in the L-PRP group, indicating that L-PRP evoked an active cellular response. Indirect osteogenesis was significantly higher on days 7, 14, and 28, and the osseointegration rate was significantly higher on day 28 in the L-PRP group compared with the control group.

Conclusions

L-PRP enhances osseointegration by promoting mesenchymal cell proliferation, osteoclastic and osteoblastic activities, and indirect osteogenesis.

导言骨结合是种植体与骨的直接接触,可通过直接和/或间接成骨来实现。富血小板血浆可加速组织再生、伤口愈合和骨结合。本研究旨在分析在小鼠上颌骨植入种植体后,白细胞和富血小板血浆(L-PRP)对直接和间接成骨的影响。方法从 4-8 周大的雄性 ICR 小鼠尾静脉采集血液,经双旋循环离心后获得 L-PRP。在深麻醉状态下拔除 4 周大 ICR 小鼠的右上第一磨牙后,用钻头准备牙槽窝,然后将喷砂过羟基磷灰石/β-磷酸三钙的钛种植体植入充满 1.5 μL L-PRP 的空腔中。结果术后第 3 天和第 5 天,L-PRP 组的细胞增殖明显高于对照组。L-PRP组破骨细胞和成骨细胞的活性在术后第5天明显增加,表明L-PRP诱发了活跃的细胞反应。与对照组相比,L-PRP 组第 7、14 和 28 天的间接成骨率明显更高,第 28 天的骨结合率也明显更高。
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引用次数: 0
Calcium oscillations and mitochondrial enzymes in stem cells 干细胞中的钙振荡和线粒体酶
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.09.002
Mio Fukuoka , Woojin Kang , Sae Horiike , Mitsutoshi Yamada , Kenji Miyado

Calcium oscillations are rhythmic fluctuations of the intracellular concentration of calcium ions (Ca2+). As Ca2+ evokes various cellular processes, its intracellular concentration is tightly regulated. Ca2+ oscillations control biological events, including neuronal differentiation and proliferation of mesenchymal stem cells. The frequency and pattern of Ca2+ oscillations depend on cell type. Researchers have studied Ca2+ oscillations to better understand how cells communicate and regulate physiological processes. Dysregulation of Ca2+ oscillations causes health problems, such as neurodegenerative disorders. This review discusses the potential functions of Ca2+ oscillations in stem cells.

钙振荡是细胞内钙离子(Ca2+)浓度的节律性波动。由于 Ca2+ 会诱发各种细胞过程,因此其细胞内浓度受到严格调控。Ca2+ 振荡控制着包括神经元分化和间充质干细胞增殖在内的生物事件。Ca2+ 振荡的频率和模式取决于细胞类型。研究人员对 Ca2+ 振荡进行了研究,以更好地了解细胞如何交流和调节生理过程。Ca2+振荡失调会导致健康问题,如神经退行性疾病。本综述讨论干细胞中Ca2+振荡的潜在功能。
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引用次数: 0
In situ forming Hydrogel with adding ZnO Nano-particle for effectively methicillin-resistant Staphylococcus aureus infected frostbite injury 添加氧化锌纳米粒子的原位成型水凝胶可有效治疗耐甲氧西林金黄色葡萄球菌感染的冻伤
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.10.008
Xun Xu , Jun Wang , Tian-Ci Sun , Qing Li , Ren-De Ning
Hydrogel has emerged as a promising wound dressing material, and in situ forming hydrogel has emerged as a promising wound dressing recently. But most in situ forming hydrogel are normally unstable. Herein, we report an in-situ forming hydrogel synthesized from poly(Nisopropylacrylamide166-co-n-butyl acrylate9)-poly(ethyleneglycol)-poly(N-isopropylacrylamide166-co-n-butyl acrylate9) copolymer (P(NIPAM166-co-nBA9)-PEG-P(NIPAM166-conBA9), denoted as PEP) and zinc oxide nano-particle(ZnO nano-particle) in response to skin temperature. This thermoresponsive hydrogel exhibits sol-gel reversibility at high temperatures, which is closed to the temperature of human skin. To investigate its healing effects, we used the Hydrogel dressing® in an SD rat model. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus(MRSA) of this PEP-ZnO hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected frostbitten skin Injury.

Materials and methods

Thirty rats were randomly divided into two groups. The treatment group received hydrogel and transparent film dressing 30 min to 1 h post-burn, while the control group received only cotton dressing. The wound area was measured, and the wound closure rate was calculated on days 3, 7, and 14 post-surgery. Tissue samples were collected from each rat on these days and stored at −80 °C for histological analysis using H&E, Masson and immunohistochemical staining. This analysis assessed factors such as granulation tissue length, re-epithelialization, re-angiogenesis, collagen deposition, inflammatory cell infiltration, and collagen production. Clinical and histological assessments at 14 days showed more rapid healing in the hydrogel dressing group compared to the control group.

Conclusion

Our results indicate that the design of our hydrogel for cooling injury wounds effectively improves healing and mitigates the damage from low temperatures.
水凝胶已成为一种前景广阔的伤口敷料材料,而原位成型水凝胶最近也成为一种前景广阔的伤口敷料。但大多数原位成型水凝胶通常都不稳定。在此,我们报告了一种由聚(Nisopropylacrylamide166-co-n-butylacrylate9)-聚(乙二醇)-聚(Nisopropylacrylamide166-co-n-butylacrylate9)共聚物(P(NIPAM166-co-nBA9)-PEG-P(NIPAM166-conBA9)合成的原位成型水凝胶、简称 PEP)和氧化锌纳米粒子(ZnO 纳米粒子)对皮肤温度的反应。这种热致伸缩性水凝胶在高温下表现出溶胶-凝胶可逆性,接近人体皮肤的温度。为了研究其愈合效果,我们在 SD 大鼠模型中使用了 Hydrogel dressing®。这种 PEP-ZnO 水凝胶伤口敷料的生物相容性和对耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌能力在体外和体内都得到了证实,它能透明地促进受 MRSA 感染的冻伤皮肤伤口的愈合。治疗组在烧伤后 30 分钟至 1 小时内使用水凝胶和透明薄膜敷料,对照组仅使用棉布敷料。在术后第 3、7 和 14 天测量伤口面积并计算伤口闭合率。在这些天收集每只大鼠的组织样本,并保存在 -80 °C,使用 H&E、Masson 和免疫组化染色法进行组织学分析。该分析评估了肉芽组织长度、再上皮化、再血管生成、胶原沉积、炎症细胞浸润和胶原生成等因素。14 天的临床和组织学评估显示,与对照组相比,水凝胶敷料组的伤口愈合更快。
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引用次数: 0
Design and development of pH-responsive levofloxacin-loaded metal-organic framework for the promising treatment of pediatric abdominal wound repair 设计和开发 pH 值响应型左氧氟沙星负载金属有机框架,有望用于治疗小儿腹部伤口修复
IF 4.3 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.05.003
Guoyan Wang , Hongwei Li , Xinhua Shao , Shuisheng Teng , Qiong Wu

With over 9 million fatalities per year expected by 2030, infectious diseases will remain a significant burden on the world economy and cause high mortality rates. An excellent method to increase the bioactivity of levofloxacin (LEV) in pediatric abdominal wound repair is the finding of a stimuli-based drug delivery system (DDS). We designed and developed an LEV incorporated with zeolite imidazole framework-8 (ZIF-8) as a promising nanocarrier for wound healing applications. The spectral analysis and morphological analysis confirm the formation of our newly fabricated composites. Mouse embryonic fibroblast NIH3T3 cells, the cytotoxicity, cytocompatibility, and cell proliferation characteristics of LEV@ZIF-8 were evaluated in vitro. LEV@ZIF-8 composite considerably improved the biocompatibility against NIH3T3 cells after 72-h of exposure, according to in vitro experiments. Under acidic circumstances, the pH-responsive drug release studies exhibit superior LEV release, and in physiological circumstances, there is no unintended drug release. The LEV@ZIF-8 composite-treated cells demonstrate the most remarkable cell growth and migration method in a very short time, according to the results of the wound scratch experiment. The composite exposure concentration depended on inhibition against various microorganisms in the antibacterial activity testing. According to the study, LEV@ZIF-8 are appropriate and effective DDS for stimuli-based pediatric abdominal wound repair.

预计到 2030 年,每年死亡人数将超过 900 万,传染病仍将是世界经济的沉重负担,并导致高死亡率。在小儿腹部伤口修复中,提高左氧氟沙星(LEV)生物活性的一个绝佳方法是找到一种基于刺激的给药系统(DDS)。我们设计并开发了一种与沸石咪唑框架-8(ZIF-8)结合的左氧氟沙星,作为一种很有前景的纳米载体用于伤口愈合应用。光谱分析和形态分析证实了我们新制造的复合材料的形成。在小鼠胚胎成纤维细胞 NIH3T3 中,对 LEV@ZIF-8 的细胞毒性、细胞相容性和细胞增殖特性进行了体外评估。体外实验结果表明,LEV@ZIF-8 复合材料与 NIH3T3 细胞接触 72 小时后,其生物相容性显著提高。在酸性环境下,pH 值响应药物释放研究显示了 LEV 的良好释放性能,而在生理环境下,则没有意外的药物释放。伤口划痕实验结果表明,LEV@ZIF-8 复合材料处理过的细胞在很短的时间内就表现出了最显著的细胞生长和迁移方法。在抗菌活性测试中,复合材料的暴露浓度取决于对各种微生物的抑制作用。研究结果表明,LEV@ZIF-8 是用于刺激性小儿腹部伤口修复的合适而有效的 DDS。
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引用次数: 0
Induction of periodontal ligament-derived mesenchymal stromal cell-like cells from human induced pluripotent stem cells 从人类诱导多能干细胞中诱导牙周韧带间充质基质细胞样细胞
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-01 DOI: 10.1016/j.reth.2024.05.005
Jiacheng Wang, Kazuki Morita, Takanori Iwata

Introduction

Periodontal disease is a common oral infection which affects the tooth-supportive tissues directly. Considering the limitation of present regenerative treatments for severe periodontal cases, cytotherapies have been gradually introduced. Human periodontal ligament-derived mesenchymal stromal cells (hPDLMSCs), while identified as one of the promising cell sources for periodontal regenerative therapy, still hold some problems in the clinical application especially their limited life span. To solve the problems, human induced pluripotent stem cells (hiPSCs) are taken into consideration as a robust supply for hPDLMSCs.

Methods

The induction of hPDLMSCs was performed based on the generation of neural crest-like cells (NCLCs) from hiPSCs. Fibronectin and laminin were tested as coating materials for NCLCs differentiation when following previous protocol, and the characteristics of induced cells were identified by flow cytometry and RT-qPCR for evaluating the induction efficiency. Subsequently, selected dental ectoderm signaling-related cytokines were applied for hPDLMSCs induction for 14 days, and dental mesenchyme-related genes, dental follicle-related genes and hPDL-related genes were tested by RT-qPCR for the evaluation of differentiation.

Results

Compared to the 58% in laminin-coated condition, fibronectin-coated condition had a higher induction efficiency of CD271high cells as 86% after 8-day induction, while the mesenchymal potential of induced NCLCs was similar between two coating materials.

It was shown that the gene expressions of dental mesenchyme, dental follicles and hPDL cells were significantly enhanced with the stimulation of the combination with fibroblast growth factor 8b (FGF8b), FGF2, and bone morphogenetic protein 4 (BMP4).

Conclusion

FN coating was more effective in NCLCs induction, and the FGF8b+FGF2+BMP4 growth factor cocktail was effective in hPDLMSC-like cell generation. These findings underscored the likely regenerative potential of hiPSCs as an applicable and promising curative strategy for periodontal diseases.

导言牙周病是一种常见的口腔感染,直接影响牙齿的支持组织。考虑到目前针对严重牙周病的再生治疗方法的局限性,细胞疗法逐渐被引入。人牙周韧带间充质基质细胞(hPDLMSCs)虽然被认为是牙周再生治疗的理想细胞来源之一,但在临床应用中仍存在一些问题,尤其是其寿命有限。为了解决这些问题,人类诱导多能干细胞(hiPSCs)被认为是 hPDLMSCs 的可靠来源。按照先前的方案,测试了纤连蛋白和层粘连蛋白作为NCLCs分化的包被材料,并通过流式细胞术和RT-qPCR鉴定了诱导细胞的特征,以评估诱导效率。随后,选用与牙外胚层信号相关的细胞因子诱导 hPDLMSCs 14 天,并通过 RT-qPCR 检测牙间质相关基因、牙泡相关基因和 hPDL 相关基因以评估分化情况。结果与层粘连蛋白包被条件下的 58% 相比,纤维粘连蛋白包被条件下的 CD271 高细胞诱导效率更高,8 天后达到 86%,而两种包被材料诱导的 NCLCs 的间充质潜能相似。研究表明,在成纤维细胞生长因子 8b (FGF8b)、FGF2 和骨形态发生蛋白 4 (BMP4) 的联合刺激下,牙间质、牙泡和 hPDL 细胞的基因表达明显增强。这些研究结果表明,hiPSCs 具有再生潜力,是治疗牙周疾病的一种适用且前景广阔的策略。
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Regenerative Therapy
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