Tissue Engineering Part A最新文献

{"title":"Hydrogel-Encapsulated Primed MSCs Enhance Regeneration in Full-Thickness Porcine Burn Wounds.","authors":"Kristopher White, Victor Pozzo, Alec R Andrews, Rabab Chalaby, Annie T Dinh, Pierre Tawa, Golda Romano, Alexandre G Lellouch, Curtis L Cetrulo, Ronke Olabisi","doi":"10.1177/19373341261460268","DOIUrl":"10.1177/19373341261460268","url":null,"abstract":"<p><p>Severe burn injuries pose significant clinical challenges, with high risks of infection, excessive inflammation, and impaired wound healing. Mesenchymal stem cells (MSCs) have shown regenerative and antimicrobial potential; however, their therapeutic efficacy is constrained by poor survival and engraftment. Here, we demonstrate that priming MSCs with insulin-secreting cells (ISCs) and encapsulating them in hydrogels (HEMI) enhances their regenerative function, leading to accelerated healing of full-thickness burns in a porcine model. By 5 weeks, 80% of HEMI-treated wounds achieved complete closure, compared with 50% of MSC-only wounds and 0% of standard-of-care control wounds. All groups exhibited partial wound closure over time, but no control wounds reached complete closure within the study period. Histological analysis revealed complete epidermal and dermal regeneration with minimal fibrosis in HEMI-treated wounds. Single-cell RNA sequencing and differentially abundant sequencing analysis identified distinct MSC subpopulations whose relative abundance and transcriptional profiles differed between insulin-primed and control MSCs, with insulin priming promoting pathways involved in extracellular matrix stabilization, immune modulation, and oxidative stress resistance. Our findings suggest that insulin priming enhances MSC-mediated tissue repair via paracrine mechanisms, providing a clinically translatable strategy for improving burn treatment and regenerative medicine applications.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261460268"},"PeriodicalIF":2.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354828","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":"Unidirectional Porous Carbonate Apatite Fabricated by Gelatin-Based Freeze Casting for Bone Regeneration.","authors":"Zhanrui Lou, Ryo Kishida, Pery Freitas, Kunio Ishikawa","doi":"10.1177/19373341261463761","DOIUrl":"https://doi.org/10.1177/19373341261463761","url":null,"abstract":"<p><p>To develop bone grafts with superior osteoconductivity, we have fabricated unidirectionally connected porous carbonate apatite (CAp) via gelatin gelation combined with freeze-drying. A composite of calcium carbonate (CaCO₃) and gelatin was first gelled at low temperature and then subjected to directional freeze-drying to create well-aligned macroporous channels. The samples were then sintered to remove the organic components and subsequently phosphatized to convert the composition into CAp. The resulting material exhibited a porosity exceeding 80% with fully interconnected unidirectional pores favorable for cell migration and vascular infiltration. Bone regeneration was evaluated by implanting the material into rabbit femoral bone defects; a comparison was also made with nonoriented porous controls. Histological and radiographical analyses demonstrated that the unidirectional porous structure significantly enhanced directional ingrowth of new bone tissue and accelerated early-stage bone formation relative to the control. This study demonstrates that unidirectional porous CAp fabricated via a gelatin-based freeze-casting method is promising for bone regeneration, particularly in clinical applications requiring guided bone formation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261463761"},"PeriodicalIF":2.8,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347268","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":"Regenerative Nanoscaffolds for Chronic Tympanic Membrane Perforation: From Bench to Clinical Translation.","authors":"Woochan Kim, Sang Won Beom, Selin Choi, Hye Won Yang, Dream Kim, Shinyull Lee, Harshita Sharma, Chaeyeon Park, Seong Jun Choi, Jangho Kim","doi":"10.1177/19373341261463759","DOIUrl":"https://doi.org/10.1177/19373341261463759","url":null,"abstract":"<p><p>Chronic tympanic membrane (TM) perforation remains difficult to resolve without surgery because of poor intrinsic healing capacity and limitations of passive, nonsurgical materials. Although patch-based approaches are common, most merely provide passive coverage and lack intrinsic therapeutic capability to drive tissue regeneration. We developed and clinically evaluated an extracellular matrix (ECM)-mimetic, drug-free nanopattern guidance (NG) patch for TM repair, marking a paradigm shift from passive coverage to active, biophysically driven regeneration. The NG patch is a biocompatible, implantable scaffold with aligned nanotopography that recapitulates native ECM architecture, coupled with a hydrocolloid adhesive layer to ensure secure placement. In a prospective study of 18 patients, the NG patch achieved a 61% overall healing rate with 50% complete closure and no serious adverse events. In rat models, a single application induced complete healing within 2 weeks. Mechanistic <i>in vitro</i> assays demonstrated that the nanopatterned surface enhances fibroblast adhesion, alignment, and directional migration, supporting organized tissue closure. Collectively, the NG patch offers a minimally invasive approach that activates TM repair through physical cues without exogenous drugs. This first clinical evaluation of an ECM-mimetic nanotopographical scaffold introduces a strategy to redefine the standard of care for chronic TM perforation and related defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261463759"},"PeriodicalIF":2.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340933","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 Driving Force of Hierarchical Collagen Fiber Formation: A Review of Tendon, Ligament, and Meniscus Mechanobiology.","authors":"Tristan Strayer, Jennifer L Puetzer","doi":"10.1177/19373341261460256","DOIUrl":"10.1177/19373341261460256","url":null,"abstract":"<p><p>In tendons, ligaments, and menisci, collagen fibers running the length of the tissue are the primary source of strength and function. Cells assemble these fibers hierarchically from nanometer-wide fibrils into larger fibers and fascicles, increasing in size throughout development and with mechanical loading. These fibers largely do not regenerate after injury or with repair, limiting recovery options. Engineered replacements are a promising treatment option; however, it remains a challenge to produce the hierarchical collagen fibers essential to tissue strength, limiting their applications. To better repair, regenerate, and engineer these tissues, we must better understand how cells regulate hierarchical fiber formation and maintenance. It is well established that mechanical cues are critical for cell-driven hierarchical fiber formation, which cells sense through several mechanisms, such as integrin-mediated adhesions, cell-to-cell connections, mechanosensitive ion channels, primary cilia, and caveolae. These mechanisms of mechanosensation have been well studied at the fibril scale of collagen organization, but as tissues mature, the loading environment becomes more complex, with cells experiencing increasing secondary shear and compressive loads generated by the developing hierarchical structure. Mechanical cues in this environment are likely sensed through several pathways, each likely playing a role in tissue maturation and injury. There remains a clear gap in our understanding of the later stages of hierarchical fiber formation, which are crucial to better understand since large hierarchical fibers dominate the human musculoskeletal system. Here, we review the role of mechanobiology in hierarchical fiber development and maintenance, and highlight what still needs further research to better regenerate fibers in engineered replacements or <i>in vivo</i> after injury. A better understanding of the mechanisms by which cells form hierarchically organized collagen fibers could help to overcome the limitations of current tissue engineering techniques and help to create functional repairs and replacements.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261460256"},"PeriodicalIF":2.8,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334861","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":"Impact of IFN-γ-Pretreated Umbilical Cord Mesenchymal Stem Cells Implanted in Mesh on Pelvic Organ Prolapse.","authors":"Shiyu Liu, Fei Meng, Yanting Sun, Qing Zhao, Jinhua Zhou, Juan Wang, Hongmei Ding, Youguo Chen, Fangrong Shen","doi":"10.1177/19373341261460274","DOIUrl":"10.1177/19373341261460274","url":null,"abstract":"<p><p>Pelvic organ prolapse (POP) is an urgent clinical challenge, and traditional surgical treatment is limited by high recurrence rate, erosion, mesh exposure, pain, and other complications. Recently, umbilical cord mesenchymal stem cells (UMSCs) have emerged as a promising modality for tissue regeneration and Pelvic floor repair. This study aimed to assess the effectiveness of polypropylene mesh (Gynemesh^TM PS) loaded with human UMSCs (HUMSCs) primed with IFN-γ for the treatment of POP. In this study, an ideal IFN-γ concentration was chosen to stimulate HUMSCs and create an enhanced version by incorporating the activated HUMSCs onto the mesh. Balloon distension was used to create a rat POP model, and the mesh was implanted into the vaginal wall of rats. The meshes were removed at week four after implantation in order to assess the treatment effect. The improved mesh displays good biocompatibility. <i>In vitro</i> results indicate that IFN-γ stimulates HUMSC proliferation and enhances paracrine effects. <i>In vitro</i> results also demonstrate that it effectively reduces inflammation and promotes angiogenesis, collagen deposition, and cell proliferation, thereby accelerating tissue repair. Overall, this innovative therapeutic approach offers a new avenue for POP.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261460274"},"PeriodicalIF":2.8,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334915","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":"Biosponges Embedded with GDNF Enhance Neuromuscular Recovery Following Volumetric Muscle Loss.","authors":"Jamshid Tadiwala, Connor Tobo, Kevin D Sekerak, Rebecca Sheetz, Amelia Ridolfo, Madhushika Elabada Gamage, Elif G Ertugral, Paul Jelliss, Matthew D Wood, Chandrasekhar R Kothapalli, Koyal Garg","doi":"10.1177/19373341261460266","DOIUrl":"10.1177/19373341261460266","url":null,"abstract":"<p><p>Volumetric muscle loss (VML) injuries result in an irrecoverable loss of muscle mass and function. VML injury causes loss of both contractile tissue and associated neuromuscular junctions (NMJs). Biosponge (BSG) scaffolds, composed of gelatin, collagen, and laminin-111, have improved recovery following VML. However, improvements in NMJ quantity were not observed. Glial cell line-derived neurotrophic factor (GDNF) is known to promote motor unit survival and stimulate neurite outgrowth. In this work, BSG scaffolds were electrostatically coupled with GDNF via gelatin nanoparticles (GNPs) to support myofiber regeneration and preserve NMJs post-VML in a rodent model. <i>In vitro</i> determination of release kinetics revealed an initial burst release of surface-bound GDNF with almost an equivalent amount of electrostatically bound GDNF retained within the BSG post 1 week of incubation at 37°C in phosphate-buffered saline. To create the VML injury in male Lewis rats (10-12 weeks old), ∼20% of the muscle mass was removed from the tibialis anterior (TA) muscle of both hindlimbs. Relative to BSG + GNP alone, treatment with BSG + GNP + GDNF showed a significant increase (∼25%) in peak isometric torque at 6 weeks postinjury. Qualitative and quantitative histological analysis of NMJs revealed an enhanced overlap between pre and postsynaptic structures in the BSG + GNP + GDNF group. Additionally, the incorporation of GDNF slowed BSG remodeling and degradation. Overall, these results suggest that BSG-mediated GDNF delivery is an effective strategy for mitigating NMJ loss and enhancing muscle recovery following VML.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261460266"},"PeriodicalIF":2.8,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304126","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 Nondestructive Raman Spectral Method for Temporal Tracking of Articular Cartilage Maturation.","authors":"Nathan J Castro, Greta Babakhanova, Ryan Donahue, Benjamin Bielajew, Jerry Hu, Kyriacos A Athanasiou","doi":"10.1177/19373341261447726","DOIUrl":"https://doi.org/10.1177/19373341261447726","url":null,"abstract":"<p><p>Because articular cartilage (AC) lacks inherent repair capacity, research has focused on translating tissue-engineered cartilage to the clinic. Toward this, rapid and nondestructive methods would be useful for determining in-process and release characteristics during the manufacture of tissue-engineered products. The current work aims to introduce a Raman-based methodology for nondestructive qualitative and quantitative characterization of tissue development using AC. First, Raman shifts associated with critical biochemical components of AC, with particular emphasis on DNA, glycosaminoglycans (long chains of sugar molecules and a key component of cartilage), total collagen, as well as pyridinoline (a marker of collagen crosslinking and maturation), were collated. Next, verification of the molecular spectroscopic biomarkers was conducted by temporally tracking tissue maturation/development of nascent and mature AC, establishing a temporal reference dataset. Finally, validation was performed by correlating the spectroscopic biomarkers with traditional photometric biochemical assays and mass spectrometry. The results presented here include a Maturity Index for quantification of tissue development/maturation. Strong correlations were found between nondestructive spectroscopic-based measurements and destructive (photometric and mass spectrometric) measurements with high linearity for both nondestructive Raman (<i>R</i>² > 0.96) and destructive biochemical (<i>R</i>² > 0.97) assays, respectively. Uses of the proposed rapid and nondestructive method include in-line quality assessment (in which the sample is not removed from the process stream) to monitor the manufacturing of tissue-engineered medical products. This study shows that Raman spectroscopy has the capacity of being a powerful tool for nondestructive quality control and assurance in traditional biomanufacturing workflows, and the approach taken here may also be utilized as a template and research tool for studies on the development of other native and engineered tissues.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261447726"},"PeriodicalIF":2.8,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304177","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":"Radiation Modulates the Mechanoresponse of Bone-Homing Triple-Negative Breast Cancer Cells.","authors":"Shreya Venkatesh, Andrea Ordonez, William R Thompson, Edward B Chuong, Maureen E Lynch","doi":"10.1177/19373341261449883","DOIUrl":"https://doi.org/10.1177/19373341261449883","url":null,"abstract":"<p><p>Bone is a common site of breast cancer metastasis, which dramatically increases fracture risk. Recent <i>in vivo</i> bone metastasis studies show that mechanical loading is osteoprotective; however, little is known about how loading regulates breast cancer cell function in the unique bone mechanical environment, especially in combination with radiotherapy, one of the first-line treatments for advanced breast cancer patients. Here, we characterize the breast cancer cell response to a range of bone-mimicking fluid shears and determine how irradiation further modulates one candidate gene: <i>SERPINE1</i>. We found that irradiation, regardless of dosage, modulates <i>SERPINE1</i> expression and is sensitive to the timing of administration. Additionally, protein expression of <i>SERPINE1</i> accompanies a protumorigenic gene expression profile, which is elevated with higher-magnitude fluid shear stresses in a bone-mimicking 3D environment. Thus, we postulate that plasminogen activator inhibitor-1 (PAI-1) (encoded by <i>SERPINE1</i>) is a critical growth factor contributing to osteolytic lesion development in the bone metastatic vicious cycle of breast cancer.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261449883"},"PeriodicalIF":2.9,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221182","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 New Bioprinted Dual-Layered Corneal Structure Using Collagen-Based Bioinks.","authors":"Huasheng Huang, Yunong Yuan, Yuan Fang, Chris Hodge, Constantinos Pestglou, Gordon G Wallace, Gerard Sutton, Jingjing You","doi":"10.1177/19373341261424272","DOIUrl":"10.1177/19373341261424272","url":null,"abstract":"<p><p>Bioengineered corneal constructs are a promising solution to the global shortage of donor tissue. However, most current models lack anatomical curvature and appropriate extracellular matrix (ECM) composition of the native cornea, limiting their relevance for studying graft integration and stromal-endothelial interactions. In this study, we developed a bioprinted, dual-layer corneal model comprising corneal stromal cells laden in type I collagen (Col-I) and a monolayer of corneal endothelial cells supported by collagen type IV (Col-IV). The construct was printed onto a curved support to replicate the posterior curvature of the native cornea. The use of ECM-specific, human-derived collagen bioinks supported high cell viability (>90%) and the formation of a continuous endothelial layer. Histological and immunofluorescence analyses confirmed distinct layering and appropriate cellular morphology and phenotypic marker expression for both corneal stromal and endothelial cells. The construct retained its curvature, transparency, and interfacial integrity over 3 weeks in culture and demonstrated adherence when positioned over an <i>ex vivo</i> corneal tissue. This anatomically curved, multilayered <i>in vitro</i> model offers a physiologically relevant platform for exploring stromal-endothelial architecture and cell interaction in corneal tissue engineering applications.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"423-436"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313104","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":"Plasma Surface Modification of 3D Printed Scaffolds for Neurovascularized Nipple-Areolar Complexes.","authors":"Caitlin R O'Donnell, M Azam Ali, Jaydee D Cabral","doi":"10.1177/19373341251404450","DOIUrl":"10.1177/19373341251404450","url":null,"abstract":"<p><p>For individuals undergoing mastectomy, reconstruction of the nipple-areola complex (NAC) is a critical step in emotional and psychological recovery. However, current clinical approaches-including flap suturing, tattooing, or grafting-are limited by loss of projection, poor mechanical stability, and absence of sensation. Additive manufacturing and tissue engineering offer promising alternatives by enabling the development of hybrid scaffolds that maintain long-term projection and support the potential return of sensation. This review summarizes the state-of-the-art in NAC reconstruction and highlights how advances in additive manufacturing can address existing limitations. Emerging scaffold design strategies allow precise fabrication of biomimetic architectures that replicate the anatomical form and function of the NAC, while supporting tissue integration and mechanical durability. The use of biocompatible polymers such as poly-ε-caprolactone, combined with bioactive coatings and plasma surface modification, enhances cell attachment and vascularization. Additionally, the incorporation of stem cells, multicellular constructs, and conducting polymers is explored to enable multifunctional tissue regeneration and restore sensation through electrical stimulation. By integrating innovations in biomaterials science, regenerative medicine, and advanced fabrication technologies, the field is moving toward nipple reconstructions that are not only more life-like in appearance but also biologically responsive and sensate.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"379-392"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859230","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}