Tissue Engineering Part A最新文献

{"title":"Amino Acid Uptake Limitations during Human Mesenchymal Stem Cell-Based Chondrogenesis.","authors":"Yi Zhong, Bo Zhang, Rodrigo Somoza, Arnold I Caplan, Jean F Welter, Harihara Baskaran","doi":"10.1089/ten.TEA.2024.0032","DOIUrl":"10.1089/ten.TEA.2024.0032","url":null,"abstract":"<p><p>A mino acids are the essential building blocks for collagen and proteoglycan, which are the main constituents for cartilage extracellular matrix (ECM). Synthesis of ECM proteins requires the uptake of various essential/nonessential amino acids. Analyzing amino acid metabolism during chondrogenesis can help to relate tissue quality to amino acid metabolism under different conditions. In our study, we studied amino acid uptake/secretion using human mesenchymal stem cell (hMSC)-based aggregate chondrogenesis in a serum-free induction medium with a defined chemical formulation. The initial glucose level and medium-change frequency were varied. Our results showed that essential amino acid uptake increased with time during hMSCs chondrogenesis for all initial glucose levels and medium-change frequencies. Essential amino acid uptake rates were initial glucose-level independent. The DNA-normalized glycosaminoglycans and hydroxyproline content of chondrogenic aggregates correlated with cumulative uptake of leucine, valine, and tryptophan regardless of initial glucose levels and medium-change frequencies. Collectively, our results show that amino acid uptake rates during <i>in vitro</i> chondrogenesis were insufficient to produce a tissue with an ECM content similar to that of human neonatal cartilage or adult cartilage. Furthermore, this deficiency was likely related to the downregulation of some key amino acid transporters in the cells. Such deficiency could be partially improved by increasing the amino acid availability in the chondrogenic medium by changing culture conditions.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"1-12"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologic Doses of Transforming Growth Factor-β Improve the Composition of Engineered Articular Cartilage.","authors":"Tianbai Wang, Sedat Dogru, Zhonghao Dai, Sung Yeon Kim, Nicholas A Vickers, Michael B Albro","doi":"10.1089/ten.TEA.2023.0360","DOIUrl":"10.1089/ten.TEA.2023.0360","url":null,"abstract":"<p><p>Conventionally, for cartilage tissue engineering applications, transforming growth factor beta (TGF-β) is administered at doses that are several orders of magnitude higher than those present during native cartilage development. While these doses accelerate extracellular matrix (ECM) biosynthesis, they may also contribute to features detrimental to hyaline cartilage function, including tissue swelling, type I collagen (COL-I) deposition, cellular hypertrophy, and cellular hyperplasia. In contrast, during native cartilage development, chondrocytes are exposed to moderate TGF-β levels, which serve to promote strong biosynthetic enhancements while mitigating risks of pathology associated with TGF-β excesses. Here, we examine the hypothesis that physiologic doses of TGF-β can yield neocartilage with a more hyaline cartilage-like composition and structure relative to conventionally administered supraphysiologic doses. This hypothesis was examined on a model system of reduced-size constructs (∅2 × 2 mm or ∅3 × 2 mm) comprised of bovine chondrocytes encapsulated in agarose, which exhibit mitigated TGF-β spatial gradients allowing for an evaluation of the intrinsic effect of TGF-β doses on tissue development. Reduced-size (∅2 × 2 mm or ∅3 × 2 mm) and conventional-size constructs (∅4-∅6 mm × 2 mm) were subjected to a range of physiologic (0.1, 0.3, 1 ng/mL) and supraphysiologic (3, 10 ng/mL) TGF-β doses. At day 56, the physiologic 0.3 ng/mL dose yielded reduced-size constructs with native cartilage-matched Young's modulus (E_Y) (630 ± 58 kPa) and sulfated glycosaminoglycan (sGAG) content (5.9 ± 0.6%) while significantly increasing the sGAG-to-collagen ratio, leading to significantly reduced tissue swelling relative to constructs exposed to the supraphysiologic 10 ng/mL TGF-β dose. Furthermore, reduced-size constructs exposed to the 0.3 ng/mL dose exhibited a significant reduction in fibrocartilage-associated COL-I and a 77% reduction in the fraction of chondrocytes present in a clustered morphology, relative to the supraphysiologic 10 ng/mL dose (<i>p</i> < 0.001). E_Y was significantly lower for conventional-size constructs exposed to physiologic doses due to TGF-β transport limitations in these larger tissues (<i>p</i> < 0.001). Overall, physiologic TGF-β appears to achieve an important balance of promoting requisite ECM biosynthesis, while mitigating features detrimental to hyaline cartilage function. While reduced-size constructs are not suitable for the repair of clinical-size cartilage lesions, insights from this work can inform TGF-β dosing requirements for emerging scaffold release or nutrient channel delivery platforms capable of achieving uniform delivery of physiologic TGF-β doses to larger constructs required for clinical cartilage repair.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"56-68"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polycaprolactone/β-Tricalcium Phosphate Composite Scaffolds with Advanced Pore Geometries Promote Human Mesenchymal Stromal Cells' Osteogenic Differentiation.","authors":"Sophia Dalfino, Elena Olaret, Marco Piazzoni, Paolo Savadori, Izabela Stancu, Gianluca Tartaglia, Claudia Dolci, Lorenzo Moroni","doi":"10.1089/ten.TEA.2024.0030","DOIUrl":"10.1089/ten.TEA.2024.0030","url":null,"abstract":"<p><p>Critical-sized mandibular bone defects, arising from, for example, resections after tumor surgeries, are currently treated with autogenous bone grafts. This treatment is considered very invasive and is associated with limitations such as morbidity and graft resorption. Tissue engineering approaches propose to use 3D scaffolds that combine structural features, biomaterial properties, cells, and biomolecules to create biomimetic constructs. However, mimicking the complex anatomy and composition of the mandible poses a challenge in scaffold design. In our study, we evaluated the dual effect of complex pore geometry and material composition on the osteogenic potential of 3D printed scaffolds. The scaffolds were made of polycaprolactone (PCL) alone (TCP0), or with a high concentration of β-tricalcium phosphate (β-TCP) up to 40% <i>w/w</i> (TCP40), with two complex pore geometries, namely a star- (S) and a diamond-like (D) shape. Scanning electron microscopy and microcomputed tomography images confirmed high fidelity during the printing process. The D-scaffolds displayed higher compressive moduli than the corresponding S-scaffolds. TCP40 scaffolds in simulated body fluid showed deposition of minerals on the surface after 28 days. Subsequently, we assessed the differentiation of seeded bone marrow-derived human mesenchymal stromal cells (hMSCs) over 28 days. The early expression of <i>RUNX2</i> in the cell nuclei confirmed the commitment toward an osteogenic phenotype. Moreover, alkaline phosphatase (ALP) activity and collagen deposition displayed an increasing trend in the D-scaffolds. Collagen type I was mainly present in the deposited extracellular matrix (ECM), confirming deposition of bone matrix. Finally, Alizarin Red staining showed successful mineralization on all the TCP40 samples, with higher values for the S-shaped scaffolds. Taken together, our study demonstrated that the complex pore architectures of scaffolds comprised TCP40 stimulated osteogenic differentiation and mineralization of hMSCs <i>in vitro</i>. Future research will aim to validate these findings <i>in vivo</i>.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"13-28"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGFβ-1 and Healing of Bone Defects in Large Animal and Rabbit Models: A Systematic Review.","authors":"Sara Trbojevic, Juan M Taboas, Alejandro J Almarza","doi":"10.1089/ten.tea.2024.0226","DOIUrl":"10.1089/ten.tea.2024.0226","url":null,"abstract":"<p><p>Long bone and craniofacial bone fractures amount to an overwhelming expenditure for patients and health care systems each year. Overall, 5-10% of all bone fractures result in some form of delayed or nonunion fractures. Nonunions occur from insufficient mechanical stabilization or a compromised wound environment lacking in vasculature and progenitor cells. The current standard for treating these critical-sized fractures and defects is the use of autologous bone grafts. However, advancements in tissue engineering have cultivated a shift in scientific efforts toward harnessing the body's own regenerative resources. As such, research on fracture healing has shifted as well. Transforming growth factor-beta 1 (TGFβ-1) has been studied in fracture healing for over 25 years, though many of these studies have been <i>in vitro</i> or in small animal models. The few studies in large animals have disagreement due to the heterogeneity within the experimental design. Because TGFβ-1 plays such a crucial role in the bone healing process, this systematic review investigates the application of TGFβ-1 in various carrier vehicles for repairing bone injuries in large animal and rabbit models. A systematic search was conducted in PubMed, Embase, and Web of Science (from database construction-October 2024). A total of 244 articles were screened, and 24 studies were included for review. Most large animal long bone studies used coated titanium implants, while most rabbit long bone studies used some form of degradable polymer constructs. TGFβ-1 doses in large animal long bone studies range from 0.005 to 750 µg, doses in large animal calvaria and mandible studies range from 1 to 5000 µg, and doses in rabbit long bone studies range from 0.05 to 120 µg. Nineteen out of 24 articles reviewed indicate successful use of TGFβ-1 for bone regeneration compared with experimental controls. It is clear that dose and controlled release of growth factor play a crucial role in defect closure, but outcome measures and success criteria were inconsistent across studies. More studies with consistent experimental designs are critical for understanding the therapeutic potential of TGFβ-1 in fracture repair, but overall, this review indicates that TGFβ-1 can be used alone or in conjunction with other growth factors to accelerate successful bone repair.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of MicroRNA-100-5p Promotes Osteogenesis Via Lysine(K)-Specific Demethylase 6B.","authors":"Xiaokang Gong, Xi Chen, Zhulong Meng, Jiehe Huang, Shunjie Jia, Weiqian Wu, Lihong Li, Xin Zheng","doi":"10.1089/ten.tea.2024.0273","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0273","url":null,"abstract":"<p><p>Senescence and osteogenic differentiation potential loss limited bone nonunion treatment effects of bone marrow-derived mesenchymal stem cells (BMSCs). MiR-100-5p/Lysine(K)-specific demethylase 6B (KDM6B) can inhibit osteogenesis, but their effects on bone union remain unclear. This study aims to investigate the effects of miR-100-5p/KDM6B on osteogenic differentiation and bone defects. Wild-type or microRNA 100 (miR-100) knockdown mice underwent critical-size defect (CSD) cranial surgery and collagen I/poly-γ-glutamic acid scaffold treatment. The crania was observed using microcomputed tomography, hematoxylin and eosin staining, Masson staining, alkaline phosphatase (ALP) staining, immunohistochemistry, and immunofluorescence. Primary-cultured BMSCs transfected with miR-100-5p mimic/inhibitor and KDM6B cDNA were evaluated for osteogenic differentiation using Alizarin Red staining, ALP activity detection, and Western blot analysis. Genetic transcription levels were detected using quantitative reverse transcription polymerase chain reaction. This study found that miR-100 depletion promotes defect healing in mouse calvaria, increases the proportion of new bone and osteoblasts in calvaria, and activates the expression of KDM6B and osteocalcin (OCN) proteins, promoting the transcription of bone morphogenetic protein-2, Runt-related transcription factor 2 (Runx2), OCN, and KDM6B, while methylation of lysine 27 on histone H3 (H3K27me3) decreased. Furthermore, miR-100-5p mimics suppressed osteogenic differentiation by inhibiting KDM6B with increased H3K27me3, ALP, Runx2, OCN, and osteopontin protein expression, while miR-100-5p inhibitors have opposite effects. Moreover, KDM6B can reverse miR-100-5p mimic effects. Notably, scaffolds carrying miR-100-5p mimics/inhibitors transfected BMSCs were placed in CSD mice and found that miR-100-5p inhibitors have a better effect on CSD healing and increase new bone without inflammatory cell infiltration. This study proved that miR-100-5p depletion promotes bone union and osteogenic differentiation of BMSCs via KDM6B/H3K27me3.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association with Cationized Gelatin Nanospheres Enhances Mitochondria Uptake and Membrane Potential.","authors":"Wenxuan Yang, Satoshi Abe, Mitsuru Ando, Yasuhiko Tabata","doi":"10.1089/ten.tea.2024.0265","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0265","url":null,"abstract":"<p><p>The objective of this study is to investigate the influence of exogenous mitochondria (Mt) internalization on the Mt membrane potential of cells. Cationized gelatin nanospheres (cGNS) were prepared to mix Mt at different ratios to prepare Mt associated with cGNS (Mt-cGNS). The Mt internalization depended on the Mt/cGNS mixing ratio to achieve the maximum at the ratio of 3/1. Rho 0 cells of a Mt function-deficient line were prepared to evaluate the enhancement of Mt membrane potential of rho 0 cells after the internalization of Mt-cGNS. When evaluated by using tetramethylrhodamine methyl ester reagent, the mitochondrial membrane potential of rho 0 cells after incubation with Mt-cGNS enhanced compared with that incubated with Mt only and maintained at a significantly higher level even for 6 days. The Mt-cGNS were internalized into rho 0 cells by an actin-dependent pathway, followed by fused with endogenous Mt. It is concluded that association with the cGNS enabled Mt to enhance the cellular internalization, followed by the fusion with endogenous Mt to maintain an enhanced Mt membrane potential.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repair of Osteochondral Defect with Acellular Cartilage Matrix and Thermosensitive Hydrogel Scaffold.","authors":"Shengtao Zou, Guochao Xu, Zhenyu Zheng, Tianming Chen, Yixing Huang","doi":"10.1089/ten.tea.2024.0231","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0231","url":null,"abstract":"<p><p>In the present study, acellular cartilage matrix (ACM) was modified with poly-l-lysine/hyaluronic acid (PLL/HA) multilayers via detergent-enzyme chemical digestion and layer-by-layer self-assembly technology. This modified ACM was then loaded with Transforming Growth Factor Beta 3 (TGF-β3) and incorporated into a thermosensitive hydrogel (TH) to create a HA/PLL-ACM/TH composite scaffold with sustained-release function. This study aimed to evaluate the efficacy of this novel composite scaffold in promoting chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and facilitating osteochondral defect repair. <i>In vitro</i>, isolated, and cultured rat BMSCs were inoculated in equal amounts into TH, ACM/TH, and HA/PLL-ACM/TH groups, with or without TGF-β3 supplementation, for 21 days. Western blot (WB) analysis and immunofluorescence staining were employed to assess the expression levels of collagen II, aggrecan, and SOX-9. <i>In vivo</i>, osteochondral defect was created in the Sprague-Dawley rat trochlea using microdrilling. TH, ACM/TH, and HA/PLL-ACM/TH scaffolds, with or without TGF-β3, were implanted into the defect. After 6 weeks, the repairs were evaluated macroscopically, using Micro computed tomography (micro-CT), histological analysis, and immunohistochemistry. The results demonstrated that the HA/PLL-ACM/TH scaffold loaded with TGF-β3 significantly upregulated the expression of collagen II, aggrecan, and SOX-9 compared with the control and other experimental groups. Furthermore, at 6 weeks postsurgery, the HA/PLL-ACM/TH group loaded with TGF-β3 exhibited superior tissue formation on the joint surface, as confirmed by micro-CT and histological evidence, indicating improved osteochondral repair. These findings suggest that the HA/PLL-ACM/TH scaffold loaded with TGF-β3 holds promise as a therapeutic strategy for osteochondral defect and offers a novel approach for utilizing acellular cartilage microfilaments.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Composite Foam of Dermal Matrix-Demineralized Bone Matrix for Enhanced Bone Regeneration.","authors":"Tong Ma, Jingjing Wang, Dangli Ren, Hongtao Sun, Wendell Q Sun","doi":"10.1089/ten.tea.2024.0183","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0183","url":null,"abstract":"<p><p>Allogenic demineralized bone matrix (DBM) is widely used for bone repair and regeneration due to its osteoinductivity and osteoconductivity. The present study utilized acellular dermis microfibers to improve the DBM's clinical handling properties and to enhance bone regeneration. Donated human cadaver skin was de-epidermized and decellularized to be acellular dermal matrix (ADM), which was further processed into microfibers. Donated human bone was micronized and partially demineralized (∼30% calcium removal) for optimal bone regeneration. A flexible ADM/DBM composite foam was fabricated with ADM microfibers and DBM particles. Structural analysis found that the ADM/DBM composite foam had proper porosity with interconnected micropores and rapid wettability, and good stability upon cyclic compressions, whereas cytotoxicity test, <i>in vitro</i> collagenase degradation, and rat subcutaneous implantation showed good biocompatibility and biodegradability. The composite foam, used for <i>in vitro</i> coculture, significantly increased the alkaline phosphatase activity of C2C12 cells and upregulated the expression of osteogenesis-related genes of human umbilical cord mesenchymal stem cells. Using the rat Φ8 mm calvarium defect repair model, the ADM/DBM composite foam demonstrated superior osteogenicity by rapidly inducing new bone formation and achieving complete closure of the bone defects, as compared with the commercially available bone graft for skull repair (SkuHeal). Therefore, the ADM/DBM composite foam holds promise as a superior DBM-based product for repairing critical bone defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Low-Intensity Pulsed Ultrasound on Temporomandibular Joint Arthritis in Juvenile Rats.","authors":"Jacqueline Crossman, Hollis Lai, Marianna Kulka, Nadr Jomha, Patrick Flood, Tarek El-Bialy","doi":"10.1089/ten.TEA.2024.0034","DOIUrl":"10.1089/ten.TEA.2024.0034","url":null,"abstract":"<p><p>Juvenile idiopathic arthritis is an inflammatory disease that can affect the temporomandibular joint (TMJ) and lower jaw growth. Better treatment options are needed, so this study investigated the effect of low-intensity pulsed ultrasound (LIPUS) on TMJ arthritis. Seventy-two 3-week-old male Wistar rats were <i>in vivo</i> microcomputed tomography (micro-CT) scanned and divided into eight groups (<i>n</i> = 9). These groups were Group 1-TMJ arthritis and immediate LIPUS treatment (20 min/day, 4 weeks); Group 2-immediate LIPUS treatment and no TMJ arthritis; Group 3-TMJ arthritis and no LIPUS; Group 4-no TMJ arthritis and no LIPUS; Group 5-TMJ arthritis and LIPUS treatment with a delayed start by 4 weeks; Group 6-Delayed LIPUS and no TMJ arthritis; Group 7-TMJ arthritis and no (delayed) LIPUS; and Group 8-no TMJ arthritis and no (delayed) LIPUS. <i>Ex vivo</i> micro-CT scanning was completed, and samples were prepared for tissue analysis. Synovitis was observed in the TMJ arthritis (collagen-induced arthritis [CIA]) groups, but the severity appeared greater in the groups without LIPUS treatment. Fibrocartilage and hypertrophic cell layer thicknesses in the CIA group without LIPUS treatment were significantly greater (<i>p</i> < 0.05). Proteoglycan staining appeared greater in the LIPUS groups. Immediate LIPUS treatment increased the expression of type II collagen, type X collagen, and transforming growth factor-beta 1 (TGF-β1) immunostaining, and CIA (no LIPUS) increased MMP-13, vascular endothelial growth factor, and interleukin-1 beta (IL-1β) immunostaining. LIPUS treatment prevented growth disturbances observed in the CIA groups (no LIPUS) (<i>p</i> < 0.005). Our results have contributed to the understanding of the uses and limitations of the CIA juvenile rat model and have demonstrated the effects of LIPUS on the TMJ and mandibular growth. This information will help in designing future studies for investigating LIPUS and TMJ arthritis, leading to the development of new treatment options for children with juvenile arthritis in their TMJs.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"740-751"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Shear Stress Modulates Heterogenous Cellular Subpopulations to Induce Vascular Remodeling.","authors":"Katharina S Fischer, Dominic Henn, Eric T Zhao, Dharshan Sivaraj, Ben Litmanovich, William W Hahn, Andrew C Hostler, Sultana M Mojadidi, Javier Gonzalez, Amelia B Knochel, Maria Gracia Mora Pinos, Jared Holley, Hudson Kussie, Maia Granoski, Jonathan P Yasmeh, Ulrich Kneser, Kellen Chen, Geoffrey C Gurtner","doi":"10.1089/ten.TEA.2023.0362","DOIUrl":"10.1089/ten.TEA.2023.0362","url":null,"abstract":"<p><p><b><i>Rationale:</i></b> Elevated shear stress (ESS) induces vascular remodeling in veins exposed to arterial blood flow, which can lead to arteriovenous (AV) fistula failure. The molecular mechanisms driving remodeling have not been comprehensively examined with a single-cell resolution before. <b><i>Objective:</i></b> Using an <i>in vivo</i> animal mode, single-cell RNA sequencing, and histopathology, we precisely manipulate blood flow to comprehensively characterize all cell subpopulations important during vascular remodeling. <b><i>Methods:</i></b> AV loops were created in saphenous vessels of rats using a contralateral saphenous vein interposition graft to promote ESS. Saphenous veins with no elevated shear stress (NSS) were anastomosed as controls. <b><i>Findings:</i></b> ESS promoted transcriptional homogeneity, and NSS promoted considerable heterogeneity. Specifically, ESS endothelial cells (ECs) showed a more homogeneous transcriptional response promoting angiogenesis and upregulating endothelial-to-mesenchymal transition inhibiting genes (<i>Klf2</i>). NSS ECs upregulated antiproliferation genes such as <i>Cav1</i>, <i>Cst3</i>, and <i>Btg1</i>. In macrophages, ESS promoted a large homogeneous subpopulation, creating a mechanically activated, proinflammatory and thus proangiogenic myeloid phenotype, whereas NSS myeloid cells expressed the anti-inflammatory and antiangiogenetic marker <i>Mrc1</i>. <b><i>Conclusion:</i></b> ESS activates unified gene expression profiles to induce adaption of the vessel wall to hemodynamic alterations. Targeted depletion of the identified cellular subpopulations may lead to novel therapies to prevent excessive venous remodeling, intimal hyperplasia, and AV fistula failure.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"752-765"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}