Journal of Tissue Engineering and Regenerative Medicine最新文献

{"title":"Decellularisation and Characterisation of Porcine Pleura as Bioscaffolds in Tissue Engineering","authors":"Thirapurasundari Vikranth,&nbsp;Tina Dale,&nbsp;Nicholas R. Forsyth","doi":"10.1155/2024/9940673","DOIUrl":"https://doi.org/10.1155/2024/9940673","url":null,"abstract":"<div>\u0000 <p>Persistent air leaks caused by thoracic surgery, physical trauma, or spontaneous pneumothoraces are a cause of patient morbidity with need for extended chest tube durations and surgical interventions. Current treatment measures involve mechanical closure of air leaks in the compromised pleura. Organ and membrane decellularisation offers a broad range of biomimetic scaffolds of allogeneic and xenogeneic origins, exhibiting innate tissue-specific characteristics. We explored a physicochemical method for decellularising porcine pleural membranes (PPM) as potential tissue-engineered surrogates for lung tissue repair. Decellularised PPM (dPPM) was characterised with histology, quantitative assays, mechanical testing, and sterility evaluation. Cytotoxicity and recellularisation assays assessed biocompatibility of decellularised PPM (dPPM). Haematoxylin and Eosin (H&amp;E) staining showed an evident reduction in stained nuclei in the dPPM, confirmed with nuclear staining and analysis ( ^∗∗∗∗<i>p</i> &lt; 0.0001). Sulphated glycosaminoglycans (sGAG) and collagen histology demonstrated minimal disruption to the gross structural assembly of core extracellular matrix (ECM) in dPPM. Confocal imaging demonstrated realignment of ECM fibres in dPPM against native control. Quantitative analysis defined a significant change in the angular distribution ( ^∗∗∗∗<i>p</i> &lt; 0.0001) and coherence ( ^∗∗∗<i>p</i> &lt; 0.001) of fibre orientations in dPPM versus native ECM. DNA quantification indicated ≥85% reduction in native nuclear dsDNA in dPPM ( ^∗∗<i>p</i> &lt; 0.01). Collagen and sGAG quantification indicated reductions of both ( ^∗∗<i>p</i> &lt; 0.01). dPPM displayed increased membrane thickness ( ^∗∗∗<i>p</i> &lt; 0.001). However, Young’s modulus (459.67 ± 10.36 kPa) and ultimate tensile strength (4036.22 ± 155.1 kPa) of dPPM were comparable with those of native controls at (465.82 ± 10.51 kPa) and (3912.9 ± 247.42 kPa), respectively. <i>In vitro</i> cytotoxicity and scaffold biocompatibility assays demonstrated robust human mesothelial cell line (MeT-5A) attachment and viability. DNA quantification in reseeded dPPM with MeT-5A cells exhibited significant increase in DNA content at day 7 ( ^∗∗<i>p</i> &lt; 0.01) and day 15 ( ^∗∗∗∗<i>p</i> &lt; 0.0001) against unseeded dPPM. Here, we define a decellularisation protocol for porcine pleura that represents a step forward in their potential tissue engineering applications as bioscaffolds.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/9940673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the Regenerative Potential of Fetal Mesenchymal Stem Cells and Endothelial Colony-Forming Cells in the Biofabrication of Tissue-Engineered Vascular Grafts (TEVGs)","authors":"Angus Weekes,&nbsp;Joanna M. Wasielewska,&nbsp;Nigel Pinto,&nbsp;Jason Jenkins,&nbsp;Jatin Patel,&nbsp;Zhiyong Li,&nbsp;Travis J. Klein,&nbsp;Christoph Meinert","doi":"10.1155/2024/8707377","DOIUrl":"https://doi.org/10.1155/2024/8707377","url":null,"abstract":"<div>\u0000 <p>Tissue engineering is a promising approach for the production of small-diameter vascular grafts; however, there are limited data directly comparing the suitability of applicable cell types for vessel biofabrication. Here, we investigated the potential of adult smooth muscle cells (SMCs), placental mesenchymal stem cells (MSCs), placental endothelial colony-forming cells (ECFCs), and a combination of MSCs and ECFCs on highly porous biocompatible poly(<i>ɛ</i>-caprolactone) (PCL) scaffolds produced via melt electrowriting (MEW) for the biofabrication of tissue-engineered vascular grafts (TEVGs). Cellular attachment, proliferation, and deposition of essential extracellular matrix (ECM) components were analysed <i>in vitro</i> over four weeks. TEVGs cultured with MSCs accumulated the highest levels of collagenous components within a dense ECM, while SMCs and the coculture were more sparsely populated, ascertained via histological and immunofluorescence imaging, and biochemical assessment. Scanning electron microscopy (SEM) enabled visualisation of morphological differences in cell attachment and growth, with MSCs and SMCs infiltrating and covering scaffolds completely within the 28-day culture period. Coverage and matrix deposition by ECFCs was limited. However, ECFCs lined the ECM formed by MSCs in coculture, visualised via immunostaining. Thus, of cells investigated, placental MSCs were identified as the preferred cell source for the fabrication of tissue-engineered constructs, exhibiting extensive population of porous polymer scaffolds and production of ECM components; with the inclusion of ECFCs for luminal endothelialisation, an encouraging outcome warranting further consideration in future studies. In combination, these findings represent a substantial step toward the development of the next generation of small-diameter vascular grafts in the management of cardiovascular disease.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8707377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin Condensation Delays Senescence in Human Mesenchymal Stem Cells by Safeguarding Nuclear Damages during In Vitro Expansion","authors":"Rohit Joshi,&nbsp;Tejas Suryawanshi,&nbsp;Sourav Mukherjee,&nbsp;Shobha Shukla,&nbsp;Abhijit Majumder","doi":"10.1155/2024/1543849","DOIUrl":"10.1155/2024/1543849","url":null,"abstract":"<div>\u0000 <p>Human mesenchymal stem cells (hMSCs) are multipotent cells that differentiate into adipocytes, chondrocytes, and osteoblasts. Owing to their differentiation potential, hMSCs are among the cells most frequently used for therapeutic applications in tissue engineering and regenerative medicine. However, the number of cells obtained through isolation alone is insufficient for hMSC-based therapies and basic research, which necessitates <i>in vitro</i> expansion. Conventionally, this is often performed on rigid surfaces such as tissue culture plates (TCPs). However, during <i>in vitro</i> expansion, hMSCs lose their proliferative ability and multilineage differentiation potential, rendering them unsuitable for clinical use. Although multiple approaches have been attempted to maintain hMSC stemness during prolonged expansion, finding a suitable culture system remains an unmet need. Recently, a few research groups have shown that hMSCs maintain their stemness over long passages when cultured on soft substrates. In addition, it has been shown that hMSCs cultured on soft substrates have more condensed chromatin and lower levels of histone acetylation compared to those cultured on stiff substrates. Furthermore, it has also been shown that condensing/decondensing chromatin by deacetylation/acetylation can delay replicative senescence in hMSCs during long-term expansion on TCPs. However, the mechanism by which chromatin condensation/decondensation influences nuclear morphology and DNA damage, which are strongly related to the onset of senescence, remains unknown. To answer this question, we cultured hMSCs for long duration in the presence of epigenetic modifiers, histone acetyltransferase inhibitor (HATi), which promotes chromatin condensation by preventing histone acetylation, and histone deacetylase inhibitor (HDACi), which promotes chromatin decondensation, and investigated their effects on various nuclear markers related to senescence. We found that consistent acetylation causes severe nuclear abnormalities, whereas chromatin condensation by deacetylation helps to safeguard the nucleus from damage caused by <i>in vitro</i> expansion.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/1543849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140992901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Cell-Derived Exosomes Inhibit Osteoblast Apoptosis and Steroid-Induced Necrosis of Femoral Head Progression by Activating the PI3K/Akt/Bcl-2 Pathway","authors":"Jie Sun,&nbsp;Chen Yao,&nbsp;Wanxin Luo,&nbsp;Xingyu Ge,&nbsp;Wenjie Zheng,&nbsp;Chi Sun,&nbsp;Yafeng Zhang","doi":"10.1155/2024/3870988","DOIUrl":"10.1155/2024/3870988","url":null,"abstract":"<div>\u0000 <p>The aim of the study was to investigate the therapeutic potential of exosomes secreted by endothelial cells (EC-exos) on steroid-induced osteonecrosis of femoral head (SNFH). First, we successfully obtained EC-exos through differential centrifugation. Then, the effects of EC-exos on mouse embryo osteoblast precursor (MC3T3-E1) cells under high concentration of dexamethasone (Dex) were analysed <i>in vitro</i>, which included cell migration, viability, and apoptosis. <i>In vivo</i>, a SNFH rat model was successfully established and treated with EC-exos. Micro-computed tomography (micro-CT) and haematoxylin and eosin (H&amp;E) were used to observe femoral trabeculae. Our <i>in vitro</i> results showed that EC-exos improved cell viability and migration of osteoblasts and reduced the apoptotic effect of high concentration of Dex on osteoblasts <i>in vitro</i>. Phosphoinositide 3-kinase (PI3K)/Akt/Bcl-2 signalling pathway was activated in MC3T3-E1 cells under the response to EC-exos. <i>In vivo</i>, increased bone volume per tissue volume (BV/TV) (<i>p</i> = 0.031), trabecular thickness (Tb.Th) (<i>p</i> = 0.020), and decreased separation (Tb.Sp) (<i>p</i> = 0.040) were observed in SNFH rats treated with EC-exos. H&amp;E staining revealed fewer empty lacunae and pyknotic osteocytes in trabeculae. The expression of Bcl-2 and Akt in EC-exos group was significantly increased in trabeculae tissue. Overall, our finding indicated that EC-exos could attenuate SNFH by inhibiting osteoblast apoptosis via the PI3K/Akt/Bcl-2 pathway.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/3870988","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140991900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting of C-ROS-1 Activity Using a Controlled Release Carrier to Treat Craniosynostosis in a Preclinical Model of Saethre-Chotzen Syndrome","authors":"Esther Camp,&nbsp;Laura Gonzalez Garcia,&nbsp;Clara Pribadi,&nbsp;Sharon Paton,&nbsp;Krasimir Vasilev,&nbsp;Peter Anderson,&nbsp;Stan Gronthos","doi":"10.1155/2024/8863925","DOIUrl":"10.1155/2024/8863925","url":null,"abstract":"<div>\u0000 <p>Saethre-Chotzen syndrome (SCS) is one of the most prevalent craniosynostosis, caused by a loss-of-function mutation in the <i>TWIST-1</i> gene, with current treatment options relying on major invasive transcranial surgery. <i>TWIST-1</i> haploinsufficient osteogenic progenitor cells exhibit increased osteogenic differentiation potential due to an upregulation of the transmembrane tyrosine kinase receptor, <i>C-ROS-1</i>, a TWIST-1 target gene known to promote bone formation. The present study assessed the efficacy of suppressing C-ROS-1 activity using a known chemical inhibitor to C-ROS-1, crizotinib, to halt premature coronal suture fusion in a preclinical mouse model of SCS. Crizotinib (1 <i>μ</i>M, 2 <i>μ</i>M, or 4 <i>μ</i>M) was administered locally over the calvaria of Twist-1^del/+ heterozygous mice prior to coronal suture fusion using either a nonresorbable collagen sponge (quick drug release) or a resorbable sodium carboxymethylcellulose microdisk (slow sustained release). Coronal suture fusion rates and bone parameters were determined by <i>μ</i>CT imaging and histomorphometric analysis of calvaria postcoronal suture fusion. Results demonstrated a dose-dependent increase in the efficacy of crizotinib to maintain coronal suture patency, with no adverse effects to brain, kidney, liver, and spleen tissue, or blood cell parameters. Moreover, crizotinib delivered on microdisks resulted in a greater efficacy at a lower concentration to reduce bone formation at the coronal suture sites compared to sponges. However, the bone inhibitory effects were found to be diminished by over time following cessation of treatment. Our findings lay the foundation for the development of a pharmacological nonsurgical, targeted approach to temporarily maintain open coronal sutures in SCS patients. This study could potentially be used to develop similar therapeutic strategies to treat different syndromic craniosynostosis conditions caused by known genetic mutations.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8863925","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140997305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Varying Properties of Extracellular Matrix Grafts Impact Their Durability and Cell Attachment and Proliferation in an In Vitro Chronic Wound Model","authors":"Katrina A. Harmon,&nbsp;Miranda D. Burnette,&nbsp;Justin T. Avery,&nbsp;Kelly A. Kimmerling,&nbsp;Katie C. Mowry","doi":"10.1155/2024/6632276","DOIUrl":"https://doi.org/10.1155/2024/6632276","url":null,"abstract":"<div>\u0000 <p>While acute wounds typically progress through the phases of wound healing, chronic wounds often stall in the inflammatory phase due to elevated levels of matrix metalloproteinases (MMPs) and proinflammatory cytokines. Dysregulated expression of MMPs can result in the breakdown of extracellular matrix (ECM) formed during the wound healing process, resulting in stalled wounds. Native collagen-based wound dressings offer a potential wound management option to sequester excess MMPs and support cellular interactions that allow wound progression through the natural healing process. Herein, we utilized commercially available ECM matrices, two derived from porcine small intestinal submucosa (PCMP, 2 layers; PCMP-XT, 5 layers) and one derived from propria submucosa (ovine forestomach matrix, OFM, 1 layer), to demonstrate the impact of processing methodologies (e.g., layering and crosslinking) on functional characteristics needed for the management of chronic wounds. Grafts were evaluated for structural composition using scanning electron microscopy and histology, ability to reduce MMPs using fluorometric assays, and durability in an <i>in vitro</i> degradation chronic wound model. Both intact (nondegraded) and partially degraded grafts were assessed for their ability to serve as a functional cell scaffold using primary human fibroblasts. Grafts differed in matrix substructure and composition. While all grafts demonstrated attenuation of MMP activity, PCMP and PCMP-XT showed larger reductions of MMP levels. OFM rapidly degraded in the <i>in vitro</i> degradation model (&lt;3 hours), while PCMP and PCMP-XT were significantly more durable (&gt;7 days). The ability of PCMP and PCMP-XT to serve as scaffolds for cellular attachment was not impacted by degradation <i>in vitro</i>. Three ECM grafts with varying structural and functional characteristics exhibited differential durability when degraded in a simulated chronic wound model. Those that withstood rapid degradation maintained their ability to function as a scaffold to support attachment and proliferation of fibroblasts, a cell type important for wound healing.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/6632276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilateral Crosslinking with Glutaraldehyde and 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide: An Optimization Strategy for the Application of Decellularized Human Amniotic Membrane in Tissue Engineering","authors":"Fatemeh Alibabaei-Omran,&nbsp;Ebrahim Zabihi,&nbsp;Alexander M. Seifalian,&nbsp;Nima Javanmehr,&nbsp;Ali Samadikuchaksaraei,&nbsp;Mazaher Gholipourmalekabadi,&nbsp;Mohammad Hossein Asghari,&nbsp;Hamid Reza Nouri,&nbsp;Roghayeh Pourbagher,&nbsp;Zinatossadat Bouzari,&nbsp;Seyedali Seyedmajidi","doi":"10.1155/2024/8525930","DOIUrl":"10.1155/2024/8525930","url":null,"abstract":"<div>\u0000 <p><i>Introduction</i>. The decellularized human amniotic membrane (dHAM) emerges as a viable 3D scaffold for organ repair and replacement using a tissue engineering strategy. Glutaraldehyde (GTA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) can increase the biomechanical properties of dHAM. However, the crosslinking process is associated with biochemical changes and residual toxic materials, dampening the biocompatibility of the dHAM. From a histologic point of view, each side of the amniotic membrane is biologically different. While the dHAM basement membrane side is rich in growth factors, the stromal side of the dHAM contains more connective tissue matrix (e.g., collagen fibers) which supports its biomechanical properties. Biocompatibility and biomechanical properties are two important challenges in the field of materials science. In this study, for the first time, the stromal and basement membrane side are cross-linked with GTA and EDC, respectively, to optimize the biocompatibility of the treated dHAM while sparing the GTA-mediated biomechanical improvements. <i>Methods</i>. Crosslinking was carried out on dHAM in three groups: EDC, GTA and bilateral treatment with EDC&amp;GTA. Mechanical resistance, degradability, and crosslinking measurements were performed on treated dHAM. The viability of mesenchymal stem cells (MSCs) on the scaffolds was evaluated by the MTT assay. The expression levels of surface markers and images of the MSCs were thoroughly studied. <i>Results</i>. The results obtained showed that bilateral treatment of dHAM with EDC and GTA increased mechanical resistance. Similarly, the evaluation of surface markers revealed that bilaterally treated dHAM sustains the stemness and viability of MSCs at a level equal to that achieved with EDC alone. The SEM images indicated that the MSCs maintained adhesion on EDC&amp;GTA-cross-linked dHAM. <i>Conclusion</i>. The current study explores a pioneering treatment of dHAM, a material long recognized for its regenerative properties, in a novel context. This research delves into the utilization of dHAM cross-linked with EDC&amp;GTA, demonstrating its optimized efficacy in tissue engineering. The enhanced crosslinking technique significantly alters the membrane’s properties, amplifying its durability and therapeutic potential. In this novel bilateral treatment strategy (EDC and GTA), improving mechanical properties by GTA on the stromal surface and maintaining the biocompatibility of EDC on the side of the basement membrane of dHAM had been attained together. By investigating the handling and impact of this cross-linked membrane, this study unveils a new approach in leveraging a well-known material through an innovative process, revolutionizing its application in wound care.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8525930","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140665873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Epidermis Model Using Primary Hidradenitis Suppurativa Keratinocytes","authors":"Isabel Haferland,&nbsp;Andreas Pinter,&nbsp;Tanja Rossmanith,&nbsp;Sandra Diehl,&nbsp;Claudia Buerger,&nbsp;Tanja Ickelsheimer,&nbsp;Roland Kaufmann,&nbsp;Anke Koenig","doi":"10.1155/2024/4363876","DOIUrl":"10.1155/2024/4363876","url":null,"abstract":"<div>\u0000 <p>Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Patients can present with inflammatory nodules, abscesses up to fistulas, or sinus tracts in intertriginous body parts. Occlusion of the sebaceous gland unit leads to its rupture, with a subsequent exuberant immune response. Given there is still no causative therapy, to better understand HS and develop novel therapeutic concepts, research activities in the HS field are constantly growing. Primary skin cells, blood cells, and <i>ex vivo</i> explant cultures from HS patients have been previously used as HS cell culture models. <i>In vitro</i> reconstituted epidermal models are established to study inflammatory dermatoses, such as psoriasis or atopic dermatitis. For HS, the exploration of epidermis models would be an excellent addition, e.g., biomarkers or barrier function in testing new topic treatment options. We therefore established a stratified <i>in vitro</i> HS epidermis model based on primary cells from HS lesions. After isolating keratinocytes from lesional skin, we cultured them submerged in a transwell system. To induce differentiation, we then lifted them to the air-liquid interface. Immunohistochemical staining demonstrated that our HS-epidermis model meets the expected differentiation pattern. In addition, we detected the secretion of the inflammatory cytokines interleukin-1<i>β</i> and TNF-<i>α</i>.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/4363876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140426706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically Engineered Macrophages Derived from iPSCs for Self-Regulating Delivery of Anti-Inflammatory Biologic Drugs","authors":"Molly Klimak,&nbsp;Farshid Guilak","doi":"10.1155/2024/6201728","DOIUrl":"10.1155/2024/6201728","url":null,"abstract":"<div>\u0000 <p>In rheumatoid arthritis, dysregulated cytokine signaling has been implicated as a primary factor in chronic inflammation. Many antirheumatic and biological therapies are used to suppress joint inflammation, but despite these advances, effectiveness is not universal, and delivery is often at high doses, which can predispose patients to significant off-target effects. During chronic inflammation, the inappropriate regulation of signaling factors by macrophages accelerates the progression of disease by driving an imbalance of inflammatory cytokines, making macrophages an ideal cellular target. To develop a macrophage-based therapy to treat chronic inflammation, we engineered a novel induced pluripotent stem cell (iPSC)-derived macrophage capable of delivering soluble TNF receptor 1 (sTNFR1), an anti-inflammatory biologic inhibitor of tumor necrosis factor alpha (TNF-<i>α</i>), in an autoregulated manner in response to TNF-<i>α</i>. Murine iPSCs were differentiated into macrophages (iMACs) over a 17-day optimized protocol with continued successful differentiation confirmed at key timepoints. Varying inflammatory and immunomodulatory stimuli demonstrated traditional macrophage function and phenotypes. In response to TNF-<i>α</i>, therapeutic iMACs produced high levels of sTNFR1 in an autoregulated manner, which inhibited inflammatory signaling. This self-regulating iMAC system demonstrated the potential for macrophage-based drug delivery as a novel therapeutic approach for a variety of chronic inflammatory diseases.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/6201728","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139380725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlled Release of Mesenchymal Stem Cell-Conditioned Media from a Microsphere/Gel-Based Drug Delivery System for Wound Healing of Tympanic Membrane Perforations","authors":"Liza A. Bruk,&nbsp;Xin Fan,&nbsp;Jayde L. Resnick,&nbsp;Morgan V. DiLeo","doi":"10.1155/2023/6039254","DOIUrl":"10.1155/2023/6039254","url":null,"abstract":"<div>\u0000 <p>Chronic tympanic membrane (TM) perforation increases patient susceptibility to infection, hearing loss, and other side effects. Current clinical treatment, surgical grafting, can result in detrimental side effects including nerve damage, dizziness, or hearing loss. Therefore, it is essential to develop novel therapeutic procedures that can induce or accelerate healing in minimally or noninvasive approaches. Cell-free therapies have safety advantages over stem cells and are logistically favorable for clinical use. The regenerative potential by mesenchymal stem cell-conditioned media (CM) has been promising. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres with CM encapsulated have been developed as a cell-free alternative regenerative treatment for TM perforation. The results suggest that the PLGA microspheres were capable of encapsulating and releasing CM for up to 21 days. The <i>in vitro</i> scratch wound proliferation assays showed increased wound healing ability of CM-loaded microspheres. <i>In vivo</i> guinea pig models treated with CM drops and CM-loaded microspheres using a thermoresponsive gel carrier demonstrated potential for wound healing in TM perforation. These studies provide a basis for further examination of the delivery of stem cell CM and investigation of time-dependent wound healing, long-term ototoxicity, and hearing restoration.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2023 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2023/6039254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139132491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}