Tissue Engineering Part A最新文献

{"title":"Factors Affecting the Evaluation of Collagen Deposition and Fibrosis <i>In Vitro</i>.","authors":"Parinaz Fathi, Vanathi Sundaresan, Andrea Lucia Alfonso, Anagha Rama Varma, Kaitlyn Sadtler","doi":"10.1089/ten.TEA.2023.0284","DOIUrl":"10.1089/ten.TEA.2023.0284","url":null,"abstract":"<p><p>Immune responses to biomedical implants, wound healing, and diseased tissues often involve collagen deposition by fibroblasts and other stromal cells. Dysregulated collagen deposition can lead to complications, such as biomaterial fibrosis, cardiac fibrosis, desmoplasia, liver fibrosis, and pulmonary fibrosis, which can ultimately result in losses of organ function or failure of biomedical implants. Current <i>in vitro</i> methods to induce collagen deposition include growing the cells under macromolecular crowding conditions or on fibronectin-coated surfaces. However, the majority of these methods have been demonstrated with a single cell line, and the combined impacts of culture conditions and postculture processing on collagen deposition have not been explored in detail. In this work, the effects of macromolecular crowding versus fibronectin coating, fixation with methanol versus fixation with paraformaldehyde, and use of plastic substrates versus glass substrates were evaluated using the WI-38 human lung fibroblast cell line. Fibronectin coating was found to provide enhanced collagen deposition under macromolecular crowding conditions, while a higher plating density led to improved collagen I deposition compared with macromolecular crowding. Collagen deposition was found to be more apparent on plastic substrates than on glass substrates. The effects of primary cells versus cell lines, and mouse cells versus human cells, were evaluated using WI-38 cells, primary human lung fibroblasts, primary human dermal fibroblasts, primary mouse lung fibroblasts, primary mouse dermal fibroblasts, and the L929 mouse fibroblast cell line. Cell lines exhibited enhanced collagen I deposition compared with primary cells. Furthermore, collagen deposition was quantified with picrosirius red staining, and plate-based drug screening through picrosirius red staining of decellularized extracellular matrices was demonstrated. The results of this study provide detailed conditions under which collagen deposition can be induced <i>in vitro</i> in multiple cell types, with applications including material development, development of potential antifibrotic therapies, and mechanistic investigation of disease pathways. Impact Statement This study demonstrated the effects of cell type, biological conditions, fixative, culture substrate, and staining method on <i>in vitro</i> collagen deposition and visualization. Further the utility of plate-based picrosirius red staining of decellularized extracellular matrices for drug screening through collagen quantification was demonstrated. These results should provide clarity and a path forward for researchers who aim to conduct <i>in vitro</i> experiments on collagen deposition.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"367-380"},"PeriodicalIF":3.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Priming Enhances Chondrogenic Potential of Expanded Chondrocytes.","authors":"Adrienne K Scott, Katie M Gallagher, Stephanie E Schneider, Abhijit Kurse, Corey P Neu","doi":"10.1089/ten.TEA.2023.0170","DOIUrl":"10.1089/ten.TEA.2023.0170","url":null,"abstract":"<p><p>Expansion of chondrocytes presents a major obstacle in the cartilage regeneration procedure, such as matrix-induced autologous chondrocyte implantation. Dedifferentiation of chondrocytes during the expansion process leads to the emergence of a fibrotic (chondrofibrotic) phenotype that decreases the chondrogenic potential of the implanted cells. We aim to (1) determine the extent that chromatin architecture of H3K27me3 and H3K9me3 remodels during dedifferentiation and persists after the transfer to a three-dimensional (3D) culture; and (2) to prevent this persistent remodeling to enhance the chondrogenic potential of expanded bovine chondrocytes, used as a model system. Chromatin architecture remodeling of H3K27me3 and H3K9me3 was observed at 0 population doublings, 8 population doublings, and 16 population doublings (PD16) in a two-dimensional (2D) culture and after encapsulation of the expanded chondrocytes in a 3D hydrogel culture. Chondrocytes were treated with inhibitors of epigenetic modifiers (epigenetic priming) for PD16 and then encapsulated in 3D hydrogels. Chromatin architecture of chondrocytes and gene expression were evaluated before and after encapsulation. We observed a change in chromatin architecture of epigenetic modifications H3K27me3 and H3K9me3 during chondrocyte dedifferentiation. Although inhibiting enzymes that modify H3K27me3 and H3K9me3 did not alter the dedifferentiation process in 2D culture, applying these treatments during the 2D expansion did increase the expression of select chondrogenic genes and protein deposition of type II collagen when transferred to a 3D environment. Overall, we found that epigenetic priming of expanded bovine chondrocytes alters the cell fate when chondrocytes are later encapsulated into a 3D environment, providing a potential method to enhance the success of cartilage regeneration procedures.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"415-425"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699002","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":"Artificial Trachea from Microtissue Engineering and Three-Dimensional Printing for Tracheal Personalized Repair.","authors":"Chao Qi, Lu Cheng, Chuanqi Huang","doi":"10.1089/ten.TEA.2023.0171","DOIUrl":"10.1089/ten.TEA.2023.0171","url":null,"abstract":"<p><p>Millions of people suffer from tracheal defect worldwide each year, while autograft and allograft cannot meet existing treatment needs. Tissue-engineered trachea substitutes represent a promising treatment for tracheal defect, while lack of precisely personalized treatment abilities. Therefore, development of an artificial trachea that can be used for personalized transplantation is highly desired. In this study, we report the design and fabrication of an artificial trachea based on sericin microsphere (SM) by microtissue engineering technology and three-dimensional (3D) printing for personalized repair of tracheal defect. The SM possessed natural cell adhesion and promoting cell proliferation ability. Then, the microtissue was fabricated by coincubation of SM with chondrocytes and tracheal epithelial cells. This microtissue displayed good cytocompatibility and could support seed cell adhesion and proliferation. After that, this microtissue was individually assembled to form an artificial trachea by 3D printing. Notably, artificial trachea had an encouraging complete cartilaginous and epithelial structure after transplantation. Furthermore, the artificial trachea molecularly resembled native trachea as evidenced by similar expression of trachea-critical genes. Altogether, the work demonstrates the effectiveness of microtissue engineering and 3D printing for individual construction of artificial trachea, providing a promising approach for personalized treatment of tracheal defect.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"393-403"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543588","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":"Repairing Volumetric Muscle Loss with Commercially Available Hydrogels in an Ovine Model.","authors":"Eileen Y Su, Christopher S Kennedy, Emmanuel E Vega-Soto, Brooke D Pallas, Samantha N Lukpat, Derek H Hwang, David W Bosek, Celeste E Forester, Claudia Loebel, Lisa M Larkin","doi":"10.1089/ten.TEA.2023.0240","DOIUrl":"10.1089/ten.TEA.2023.0240","url":null,"abstract":"<p><p>Volumetric muscle loss (VML) is the loss of skeletal muscle that exceeds the muscle's self-repair mechanism and leads to permanent functional deficits. In a previous study, we demonstrated the ability of our scaffold-free, multiphasic, tissue-engineered skeletal muscle units (SMUs) to restore muscle mass and force production. However, it was observed that the full recovery of muscle structure was inhibited due to increased fibrosis in the repair site. As such, novel biomaterials such as hydrogels (HGs) may have significant potential for decreasing the acute inflammation and subsequent fibrosis, as well as enhancing skeletal muscle regeneration following VML injury and repair. The goal of the current study was to assess the biocompatibility of commercially available poly(ethylene glycol), methacrylated gelatin, and hyaluronic acid (HA) HGs in combination with our SMUs to treat VML in a clinically relevant large animal model. An acute 30% VML injury created in the sheep peroneus tertius (PT) muscle was repaired with or without HGs and assessed for acute inflammation (incision swelling) and white blood cell counts in blood for 7 days. At the 7-day time point, HA was selected as the HG to use for the combined HG/SMU repair, as it exhibited a reduced inflammation response compared to the other HGs. Six weeks after implantation, all groups were assessed for gross and histological structural recovery. The results showed that the groups repaired with an SMU (SMU-Only and SMU+HA) restored muscle mass to greater degree than the groups with only HG and that the SMU groups had PT muscle masses that were statistically indistinguishable from its uninjured contralateral PT muscle. Furthermore, the HA HG, SMU-Only, and SMU+HA groups displayed notable efficacy in diminishing pro-inflammatory markers and showed an increased number of regenerating muscle fibers in the repair site. Taken together, the data demonstrates the efficacy of HA HG in decreasing acute inflammation and fibrotic response. The combination of HA and our SMUs also holds promise to decrease acute inflammation and fibrosis and increase muscle regeneration, advancing this combination therapy toward clinically relevant interventions for VML injuries in humans.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"440-453"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814086","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":"Self-Assembly of Tooth Root Organoid from Postnatal Human Dental Stem Cells.","authors":"Tia C Calabrese, Kristi Rothermund, Claire M Gabe, Elia Beniash, Lance A Davidson, Fatima N Syed-Picard","doi":"10.1089/ten.TEA.2023.0219","DOIUrl":"10.1089/ten.TEA.2023.0219","url":null,"abstract":"<p><p>Challenges remain in simultaneously regenerating the multiple diverse tissues of the tooth root in a spatially organized manner. Previously, our research group has established that scaffold-free tissue engineering approaches enable dental pulp stem/progenitor cells (DPSCs) and periodontal ligament (PDL) stem/progenitor cells (PDLSCs) to self-assemble into dentin-pulp and PDL-cementum organoids, respectively. In this study, we leveraged the innate self-organizing capacity of DPSCs and PDLSCs to now engineer organoids that resemble the full tooth root. Scaffold-free engineered tissues were generated using a heterogeneous mixture of human DPSCs and PDLSCs. Within 2 days of construct formation, PDLSCs and DPSCs became spatially restricted to the periphery and center of the constructs, respectively, emulating their anatomical positions in the tooth root. Histological and microcomputed tomography analyses showed that organoids exhibited a striated mineral pattern with a central unmineralized core, surrounded by a mineralized tissue structure, enclosed within a second peripheral unmineralized tissue, similar to the natural tooth root. Interestingly, DPSCs gave rise to the central unmineralized tissue and the inner portion of the mineralized tissue, and PDLSCs generated the outer portion of the mineralized tissue and the peripheral soft tissue. Quantitative image analysis of immunofluorescent staining revealed increased dentin sialophosphoprotein expression in the region of mineralized tissue associated with DPSCs and increased cementum protein-1 expression in the portion formed by PDLSCs, demonstrating that tooth root organoids comprise two biochemically distinct mineralized tissues characteristic of dentin-like and cementum-like structures, respectively. In addition, PDL-associated protein-1 expression was localized to the peripheral soft tissue, suggesting the formation of a rudimentary PDL-like structure. This study demonstrates that DPSCs and PDLSCs have an inherent ability to orchestrate the formation of a full tooth root-like structure. These organoids present a biomimetic model system to study cellular dynamics driving dental tissue repair or could be utilized therapeutically as biological dental implants.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"404-414"},"PeriodicalIF":3.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138833218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Hybrid Scaffold Induces Chondrogenic Differentiation and Enhances <i>In Vivo</i> Cartilage Regeneration.","authors":"Jiaming Zhao, Zexing Yan, Yufei Ding, Yike Dai, Ziyang Feng, Zhiyao Li, Lifeng Ma, Naicheng Diao, Ai Guo, Heyong Yin","doi":"10.1089/ten.TEA.2023.0344","DOIUrl":"10.1089/ten.TEA.2023.0344","url":null,"abstract":"<p><p>Extensively researched tissue engineering strategies involve incorporating cells into suitable biomaterials, offering promising alternatives to boost tissue repair. In this study, a hybrid scaffold, Gel-DCM, which integrates a photoreactive gelatin-hyaluronic acid hydrogel (Gel) with an oriented porous decellularized cartilage matrix (DCM), was designed to facilitate chondrogenic differentiation and cartilage repair. The Gel-DCM exhibited excellent biocompatibility <i>in vitro</i>, promoting favorable survival and growth of human adipose-derived stem cells (hADSCs) and articular chondrocytes (hACs). Gene expression analysis indicated that the hACs expanded within the Gel-DCM exhibited enhanced chondrogenic phenotype. In addition, Gel-DCM promoted chondrogenesis of hADSCs without the supplementation of exogenous growth factors. Following this, <i>in vivo</i> experiments were conducted where empty Gel-DCM or Gel-DCM loaded with hACs/hADSCs were used and implanted to repair osteochondral defects in a rat model. In the control group, no implants were delivered to the injury site. Interestingly, macroscopic, histological, and microcomputed tomography scanning results revealed superior cartilage restoration and subchondral bone reconstruction in the empty Gel-DCM group compared with the control group. Moreover, both hACs-loaded and hADSCs-loaded Gel-DCM implants exhibited superior repair of hyaline cartilage and successful reconstruction of subchondral bone, whereas defects in the control groups were predominantly filled with fibrous tissue. These observations suggest that the Gel-DCM can provide an appropriate three-dimensional chondrogenic microenvironment, and its combination with reparative cell sources, ACs or ADSCs, holds great potential for facilitating cartilage regeneration.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337849","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":"Continuous Low-Intensity Ultrasound Improves Cartilage Repair in Rabbit Model of Subchondral Injury.","authors":"Anuradha Subramanian, Sarayu Bhogoju, Oraine Snaith, April D Miller, Heather Newell, Denzhi Wang, Gene Siegal, Katelin Oborny, Jesse Baumann-Berg, Hendrik Viljoen","doi":"10.1089/ten.TEA.2023.0246","DOIUrl":"10.1089/ten.TEA.2023.0246","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Subchondral drilling (SD), a bone marrow stimulation technique, is used to repair cartilage lesions that lack regenerative potential. Cartilage repair outcomes upon SD are typically fibrocartilaginous in nature with inferior functionality. The lack of cues to foster the chondrogenic differentiation of egressed mesenchymal stromal cells upon SD can be attributed for the poor outcomes. Continuous low-intensity ultrasound (cLIUS) at 3.8 MHz is proposed as a treatment modality for improving cartilage repair outcomes upon marrow stimulation. Bilateral defects were created by SD on the femoral medial condyle of female New Zealand white rabbits (&lt;i&gt;n&lt;/i&gt; = 12), and the left joint received cLIUS treatment (3.8 MHz, 3.5 Vpp, 8 min/application/day) and the contralateral right joint served as the control. On day 7 postsurgery, synovial fluid was aspirated, and the cytokine levels were assessed by Quantibody™ assay. Rabbits were euthanized at 8 weeks and outcomes were assessed macroscopically and histologically. Defect areas in the right joints exhibited boundaries, incomplete fill, irregular cartilage surfaces, loss of glycosaminoglycan (GAG), and absence of chondrocytes. In contrast, the repaired defect area in the joints that received cLIUS showed complete fill, positive staining for GAG with rounded chondrocyte morphology, COL2A1 staining, and columnar organization. Synovial fluid collected from cLIUS-treated left knee joints had lower levels of IL1, TNFα, and IFNγ when compared to untreated right knee joints, alluding to the potential of cLIUS to mitigate early inflammation. Further at 8 weeks, left knee joints (&lt;i&gt;n&lt;/i&gt; = 12) consistently scored higher on the O'Driscoll scale, with a higher percent hyaline cartilage score. No adverse impact on bone or change in the joint space was noted. Upon a single exposure of cLIUS to TNFα-treated cells, nuclear localization of pNFκB and SOX9 was visualized by double immunofluorescence and the expression of markers associated with the NFκB pathway was assayed by quantitative real-time polymerase chain reaction. cLIUS extends its chondroprotective effects by titrating pNFκB levels, preventing its nuclear translocation, while maintaining the expression of SOX9, the collagen II transcription factor. Our combined results demonstrate that healing of chondral defects treated with marrow stimulation by SD can be accelerated by employing cLIUS regimen that possesses chondroinductive and chondroprotective properties. Impact statement Repair of cartilage represents an unsolved biomedical burden. &lt;i&gt;In vitro&lt;/i&gt;, continuous low-intensity ultrasound (cLIUS) has been demonstrated to possess chondroinductive and chondroprotective potential. To our best knowledge, the use of cLIUS to improve cartilage repair outcomes upon marrow stimulation, &lt;i&gt;in vivo&lt;/i&gt;, has not been reported and our work reported here fills that gap. Our results demonstrated enhanced cartilage repair outcomes under cLIUS (3.8 MHz) in a rabbit model of s","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"357-366"},"PeriodicalIF":3.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11040182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial Cellulose Electrospun Fiber Mesh Coated with Chitin Nanofibrils for Eardrum Repair.","authors":"Bahareh Azimi, Atefeh Rasti, Alessandra Fusco, Teresa Macchi, Claudio Ricci, Mohammad Amin Hosseinifard, Lorenzo Guazzelli, Giovanna Donnarumma, Roohollah Bagherzadeh, Masoud Latifi, Ipsita Roy, Serena Danti, Andrea Lazzeri","doi":"10.1089/ten.TEA.2023.0242","DOIUrl":"10.1089/ten.TEA.2023.0242","url":null,"abstract":"<p><p>In this study, we develop a bio-based and bioactive nanofibrous patch based on bacterial cellulose (BC) and chitin nanofibrils (CNs) using an ionic liquid as a solvent for BC, aimed at tympanic membrane (TM) repair. Electrospun BC nanofiber meshes were produced via electrospinning, and surface-modified with CNs using electrospray. The rheology of the BC/ionic liquid system was investigated. The obtained CN/BC meshes underwent comprehensive morphological, physicochemical, and mechanical characterization. Cytotoxicity tests were conducted using L929 mouse fibroblasts, revealing a cell viability of 97.8%. <i>In vivo</i> tests on rabbit skin demonstrated that the patches were nonirritating. Furthermore, the CN/BC fiber meshes were tested <i>in vitro</i> using human dermal keratinocytes (HaCaT cells) and human umbilical vein endothelial cells as model cells for TM perforation healing. Both cell types demonstrated successful growth on these scaffolds. The presence of CNs resulted in improved indirect antimicrobial activity of the electrospun fiber meshes. HaCaT cells exhibited an upregulated mRNA expression at 6 and 24 h of key proinflammatory cytokines crucial for the wound healing process, indicating the potential benefits of CNs in the healing response. Overall, this study presents a natural and eco-sustainable fiber mesh with great promise for applications in TM repair, leveraging the synergistic effects of BC and CNs to possibly enhance tissue regeneration and healing. Impact statement Repair of tympanic membrane perforations following chronic otitis media is a main clinical issue in otologic surgery, where the underlying infection obstacles self-healing. To address this challenge, our study proposes a bio-based patch made of nanoscale carbohydrate materials (i.e., bacterial cellulose electrospun fibers and chitin nanofibrils) processed via green solvents. The scaffold is nonirritating <i>in vivo</i>, and cytocompatible with fibroblasts, endothelial cells, and keratinocytes. In epithelial cells, it stimulates the expression of the antimicrobial peptide human beta defensin 2, with a pathway of cytokine expression compatible with the wound healing process. Therefore, it could be applied with unsolved infective pathology.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"340-356"},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157559","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":"Macrophage Mechano-Responsiveness Within Three-Dimensional Tissue Matrix upon Mechanotherapy-Associated Strains.","authors":"Parto Babaniamansour, Diego Jacho, Ashley Teow, Agustin Rabino, Rafael Garcia-Mata, Eda Yildirim-Ayan","doi":"10.1089/ten.TEA.2023.0110","DOIUrl":"10.1089/ten.TEA.2023.0110","url":null,"abstract":"<p><p>Mechano-rehabilitation, also known as mechanotherapy, represents the forefront of noninvasive treatment for musculoskeletal (MSK) tissue disorders, encompassing conditions affecting tendons, cartilage, ligaments, and muscles. Recent emphasis has underscored the significance of macrophage presence in the healing of MSK tissues. However, a considerable gap still exists in comprehending how mechanical strains associated with mechanotherapy impact both the naïve and pro-inflammatory macrophage phenotypes within the three-dimensional (3D) tissue matrix, as well as whether the shift in macrophage phenotype is contingent on the mechanical strains inherent to mechanotherapy. In this study, we delineated alterations in mechano-adaptation and polarization of both naive and M1 macrophages within 3D matrices, elucidating their response to varying degrees of mechanical strain exposure (3%, 6%, and 12%). To evaluate macrophage mechano-adaptation and mechano-sensitivity within 3D collagen matrices under mechanical loading, we employed structural techniques (scanning electron microscopy, histology), quantitative morphological measures for phenotypic assessment, and genotypic methods such as quantitative real-time polymerase chain reaction. Our data reveal that the response of macrophages to mechanical loading is not only contingent on their specific sub-phenotype but also varies with the amplitude of mechanical strain. Notably, although supra-mechanical loading (12% strain) was requisite to induce a phenotypic shift in naive (M0) macrophages, as little as 3% mechanical strain proved sufficient to prompt phenotypic alterations in pro-inflammatory (M1) macrophages. These findings pave the way for leveraging the macrophage mechanome in customized and targeted applications of mechanical strain within the mechano-therapeutic framework. Considering the prevalence of MSK tissue injuries and their profound societal and economic implications, the development of well-informed and effective clinical mechanotherapy modalities for MSK tissue healing becomes an imperative endeavor. Impact statement Mechanotherapy is a primary noninvasive treatment for musculoskeletal (MSK) tissue injuries, but the effect of mechanical strain on macrophage phenotypes is not fully understood. A recent study found that macrophage response to mechanical loading is both sub-phenotype specific and amplitude-dependent, with even small strains enough to induce phenotypic changes in pro-inflammatory macrophages. These findings could pave the way for using macrophage mechanome in targeted mechanotherapy applications for better MSK tissue healing.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"314-329"},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11040194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influencing Endothelial Cells' Roles in Inflammation and Wound Healing Through Nucleic Acid Delivery.","authors":"Valerie Lallo, Laura G Bracaglia","doi":"10.1089/ten.TEA.2023.0296","DOIUrl":"10.1089/ten.TEA.2023.0296","url":null,"abstract":"<p><p>Tissue engineering and wound-healing interventions are often designed for use in diseased and inflamed environments. In this space, endothelial cells (ECs) are crucial regulators of inflammation and healing, as they are the primary contact for recruitment of immune cells, as well as production of proinflammatory cytokines, which can stimulate or reduce inflammation. Alternatively, proliferation and spreading of ECs result in the formation of new vascular tissue or repair of damaged tissue, both critical for wound healing. Targeting ECs with specific nucleic acids could reduce unwanted inflammation or promote tissue regeneration as needed, which are two large issues involved in many regenerative medicine goals. Polymeric delivery systems are tools that can control the delivery of nucleic acids and prolong their effects. This review describes the use of polymeric vehicles for the delivery of nucleic acids to ECs for tissue engineering. Impact statement Tissue engineering is a rapidly growing field that has the potential to resolve many disease states and improve the quality of life of patients. In some applications, tissue-engineered strategies or constructs are developed to rebuild spaces damaged by disease or degeneration. To rebuild the native tissue, these constructs may need to interact with unwanted immune activity and cells. Various immune cells are often the focus of therapies as they are critical players in the inflammatory response; however, endothelial cells are also an extremely important and promising target in these cases. In addition, controlled delivery of specific-acting molecules, such as nucleic acids, is of growing interest for the regeneration and health of a variety of different tissues. It is important to understand what has been done and the potential of these targets and therapeutics for future investigation and advancements in tissue engineering.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"272-286"},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11040193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139041024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}