Sophia Dalfino, Elena Olaret, Marco Piazzoni, Paolo Savadori, Izabela Stancu, Gianluca Tartaglia, Claudia Dolci, Lorenzo Moroni
{"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":"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}
Lan Yang, Lan Xiao, Wendong Gao, Xin Huang, Fei Wei, Qing Zhang, Yin Xiao
{"title":"Macrophages at Low-Inflammatory Status Improved Osteogenesis via Autophagy Regulation.","authors":"Lan Yang, Lan Xiao, Wendong Gao, Xin Huang, Fei Wei, Qing Zhang, Yin Xiao","doi":"10.1089/ten.TEA.2021.0015","DOIUrl":"10.1089/ten.TEA.2021.0015","url":null,"abstract":"<p><p>Accumulating evidence indicates that the interaction between immune and skeletal systems is vital in bone homeostasis. However, the detailed mechanisms between macrophage polarization and osteogenic differentiation of mesenchymal stromal cells (bone marrow-derived stromal cells [BMSCs]) remain largely unknown. We observed enhanced macrophage infiltration along with bone formation <i>in vivo</i>, which showed a transition from early-stage M1 phenotype to later stage M2 phenotype, cells at the transitional stage expressed both M1 and M2 markers that actively participated in osteogenesis, which was mimicked by stimulating macrophages with lower inflammatory stimulus (compared with typical M1). Using conditioned medium (CM) from M0, typical M1, low-inflammatory M1 (M1<sup>semi</sup>), and M2 macrophages, it was found that BMSCs treated with M1<sup>semi</sup> CM showed significantly induced migration, osteogenic differentiation, and mineralization, compared with others. Along with the induced osteogenesis, the autophagy level was the highest in M1<sup>semi</sup> CM-treated BMSCs, which was responsible for BMSC migration and osteogenic differentiation, as autophagy interruption significantly abolished this effect. This study indicated that low-inflammatory macrophages could activate autophagy in BMSCs to improve osteogenesis.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"e766-e779"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25442916","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}
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
{"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}
Nasim Annabi, Elizabeth Cosgriff-Hernandez, Anthony S Weiss
{"title":"Perspectives on Recent Developments and Directions in Tissue Engineering and Regenerative Medicine.","authors":"Nasim Annabi, Elizabeth Cosgriff-Hernandez, Anthony S Weiss","doi":"10.1089/ten.tea.2024.0313","DOIUrl":"10.1089/ten.tea.2024.0313","url":null,"abstract":"<p><p>This perspective article draws on lessons learned at the 7th TERMIS World Congress held in Seattle, Washington in June 2024. This gathering of prominent researchers and translational scientists in tissue engineering and regenerative medicine (TERM) from around the world provided a forum to consider the impact of tissue engineering and its future directions. New frontiers are considered in the context of global challenges, including clinical translation and recent advances in pediatric tissue engineering, supercritical fluid technology for scaffold fabrication and sterilization, and learning from successful failures in tissue engineering and regenerative medicine. Bench-to-bedside translational strategies, inclusive research strategies, regulatory hurdles, and ethics linked to navigating responsibilities and innovations, are identified as important drivers in the field.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"721-725"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689754","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":"An <i>In Situ</i>-Gelling Conductive Hydrogel for Potential Use in Neural Tissue Engineering.","authors":"Atefeh Amirabdollahian, Mohammad Moeini","doi":"10.1089/ten.TEA.2023.0359","DOIUrl":"10.1089/ten.TEA.2023.0359","url":null,"abstract":"<p><p>Cerebral cavitation is usual following acute brain injuries, such as stroke and traumatic brain injuries, as well as after tumor resection. Minimally invasive implantation of an injectable scaffold in the cavity is a promising approach for potential regeneration of tissue loss. This study aimed at designing an <i>in situ</i>-gelling conductive hydrogel containing silk fibroin (SF), brain decellularized extracellular matrix (dECM), and carbon nanotubes (CNT) for potential use in brain tissue regeneration. Two percent w/v SF hydrogels with different concentrations of dECM (0.1%, 0.2%, or 0.3% w/v) and CNTs (0.05%, 0.1%, or 0.25% w/v) were fabricated and characterized. It was observed that with the addition of dECM, the porosity decreased, whereas swelling and electrical conductivity tended to increase. The addition of dECM also led to a faster resorption rate, but no significant change in compressive modulus. Addition of CNTs, on the other hand, led to a denser, stronger, and more regular porous structure, higher swelling ratio, faster gelation time, slower degradation rate, and a significant increase in electrical conductivity. dECM and CNTs combined together resulted in superior porosity, swelling, resorption rate, mechanical properties, and electrical conductivity compared with SF scaffolds containing only dECM or CNTs. Hydrogel samples containing 2% SF, 0.3% dECM, and 0.1% CNTs had a high porosity (58.9%), low swelling ratio (15.9%), high conductivity (2.35 × 10<sup>-4</sup> S/m), and moderate degradation rate (37.3% after 21 days), appropriate for neural tissue engineering applications. Cell evaluation studies also showed that the hydrogel systems support the cell adhesion and growth, with no sign of significant cytotoxicity. Impact statement Tissue loss and formation of a fluid-filled cavity following stroke, traumatic brain injury, or brain tumor resection lead to sensorimotor and/or cognitive deficits. The lack of a healthy extracellular matrix in the cavity avoids the endogenous cell migration and axonal sprouting and may also worsen the secondary injuries to peri-lesional tissue. Due to the brain anatomy, simple implantation of tissue engineering scaffolds to the injured site is not possible in many cases. Therefore, the development of injectable scaffolds that support neural growth and differentiation is crucial for tissue repair or limiting the expansion of damage region.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"726-739"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041053","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 Effects of Negative Pressure Therapy on Hair Growth of Mouse Models.","authors":"Chun-Yu Cheng, Ming-Huei Cheng, Chin-Yu Yang, Cheng-Han Wang, Joshua Lim, Wei Huang, Chih-Hsin Lin","doi":"10.1089/ten.TEA.2024.0056","DOIUrl":"10.1089/ten.TEA.2024.0056","url":null,"abstract":"<p><p>Negative pressure therapy (NPT) has been shown to facilitate wound healing and promote hair growth in a porcine model. However, there is a paucity of research on the impact of negative pressure on hair growth in murine models. Despite the ability of nude mice to develop hair follicles, the hair they produce is often flawed towing to genetically induced keratin disorders, rendering them a pertinent animal model for assessing hair regeneration. Therefore, this study aims to investigate the effects of negative pressure on hair follicle growth in a nude mouse model. To achieve this, a customized external tissue expansion device was developed to apply negative pressure to the dorsum of nude mice. The mice were subjected to several treatment courses consisting of 15 and 30 min of continuous negative pressure at 10 mmHg, which were repeated 5 and 10 times every other day until sacrifice. Dorsal skin samples were subsequently extracted from the suction and nonsuction areas. The sections were stained with various antibodies to assess the expression of SOX-9, LHX-2, Keratin-15, β-catenin, CD31, and vascular endothelial growth factor-A, and a TUNEL assay was used to analyze cell apoptosis. The results showed that the number of hair follicles and angiogenesis were significantly higher in the suction area than in the nonsuction area in all groups. Moreover, mice that received NPT for 15 min for 10 times had a higher hair follicle density than the other three groups. Immunofluorescence staining for LHX-2 and Keratin 15 further validated the results of these findings. In conclusion, this study demonstrated that negative pressure effectively promotes hair follicle growth and angiogenesis in nude mice through SOX-9- and LHX-2-mediated follicular regeneration and β-catenin-mediated hair follicle morphogenesis. Impact Statement The results of this study indicate that negative pressure therapy (NPT) is effective in promoting hair growth in nude mice, as evidenced by increased hair follicle density and angiogenesis in the treated areas. Using a custom external tissue expansion device (ETED) device, 15-min NPT treatment conducted over 10 sessions demonstrated the highest follicle density. This suggest that developing a regimen for NPT may offer to create innovative treatment approaches for hair loss, ultimately benefiting individuals suffering from hair loss disorders.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"712-719"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295408","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}
Yaling Yu, Hui Liu, Ling Xu, Ping Hu, Ning Cui, Jinyi Long, Xue Wu, Da Long, Zhengbing Zhou
{"title":"Reendothelialization of Acellular Adipose Flaps under Mimetic Physiological Dynamic Conditions.","authors":"Yaling Yu, Hui Liu, Ling Xu, Ping Hu, Ning Cui, Jinyi Long, Xue Wu, Da Long, Zhengbing Zhou","doi":"10.1089/ten.TEA.2023.0340","DOIUrl":"10.1089/ten.TEA.2023.0340","url":null,"abstract":"<p><p>The extensive soft-tissue defects resulting from trauma and tumors pose a prevalent challenge in clinical practice, characterized by a high incidence rate. Autologous tissue flap transplantation, considered the gold standard for treatment, is associated with various drawbacks, including the sacrifice of donor sources, postoperative complications, and limitations in surgical techniques, thereby impeding its widespread applicability. The emergence of tissue-engineered skin flaps, notably the acellular adipose flap (AAF), offers potential alternative solutions. However, a critical concern confronting large-scale tissue-engineered skin flaps currently revolves around the reendothelialization of internal vascular networks. In our study, we have developed an AAF utilizing perfusion decellularization, demonstrating excellent physical properties. Cytocompatibility experiments have confirmed its cellular safety, and cell adhesion experiments have revealed spatial specificity in facilitating endothelial cells adhesion within the adipose flap scaffold. Using a novel mimetic physiological fluid shear stress setting, endothelial cells were dynamically inoculated and cultured within the acellular vascular network of the pedicled AAF in our research. Histological and gene expression analyses have shown that the mimetic physiological fluid dynamic model significantly enhanced the reendothelialization of the AAF. This innovative platform of acellular adipose biomaterials combined with hydrodynamics may offer valuable insights for the design and manufacturing of 3D vascularized tissue constructs, which can be applied to the repair of extensive soft-tissue defects. Impact Statement This study investigated reendothelialization of the acellular adipose flap (AAF) using 2D and 3D culture models <i>in vitro</i>. Under 2D conditions, AAF regulated endothelial cells morphology with spatial differences. A 3D mimetic physiological hydrodynamics culture model was constructed to investigate the AAF reendothelialization. Exposure of endothelial cells to physiologically fluid shear stress improved the AAF reendothelialization and increased the expression of the extracellular matrix-integrins-cytoskeleton pathway. Conversely, exposure to nonphysiological hydrodynamics and static environments decreased the reendothelialization. These findings suggest that the platform of AAF combined with physiological hydrodynamics can be applied to construct vascularized tissues to repair large-scale soft-tissue defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"693-703"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337850","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}
Martino Guiotto, Alison Clayton, Ryan Morgan, Wassim Raffoul, Andrew Hart, Mathis Riehle, Pietro di Summa
{"title":"Biogelx-IKVAV Is An Innovative Human Platelet Lysate-Adipose-Derived Stem Cells Delivery Strategy to Improve Peripheral Nerve Repair.","authors":"Martino Guiotto, Alison Clayton, Ryan Morgan, Wassim Raffoul, Andrew Hart, Mathis Riehle, Pietro di Summa","doi":"10.1089/ten.TEA.2023.0307","DOIUrl":"10.1089/ten.TEA.2023.0307","url":null,"abstract":"<p><p>Adipose-derived stem cells (ADSC) are nowadays one of the most exploited cells in regenerative medicine. They are fast growing, capable of enhancing axonal elongation, support and locally stimulate Schwann cells (SCs), and protect de-innervated muscles from atrophy after a peripheral nerve injury. With the aim of developing a bio-safe, clinically translatable cell-therapy, we assessed the effect of ADSC pre-expanded with human platelet lysate in an <i>in vivo</i> rat model, delivering the cells into a 15 mm critical-size sciatic nerve defect embedded within a laminin-peptide-functionalized hydrogel (Biogelx-IKVAV) wrapped by a poly-ɛ-caprolactone (PCL) nerve conduit. ADSC retained their stemness, their immunophenotype and proliferative activity when tested <i>in vitro</i>. At 6 weeks post-implantation, robust regeneration was observed across the critical-size gap as evaluated by both the axonal elongation (anti-NF 200) and SC proliferation (anti-S100) within the human ADSC-IKVAV filled PCL conduit. All the other experimental groups manifested significantly lower levels of growth cone elongation. The histological gastrocnemius muscle analysis was comparable with no quantitative significant differences among the experimental groups. Taken together, these results suggest that ADSC encapsulated in Biogelx-IKVAV are a potential path to improve the efficacy of nerve regeneration. New perspectives can be pursued for the development of a fully synthetic bioengineered nerve graft for the treatment of peripheral nerve injury. Impact statement Human adipose-derived stem cells pre-expanded <i>in vitro</i> with human platelet lysate culture medium additive and encapsulated into BiogelX-IKVAV are a promising strategy to improve nerve regeneration through a critical nerve gap in rat model.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"681-692"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121495","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}
Lucas Rohrer, Shinji Kato, Shane A Browne, Katharine Striedinger-Melo, Kevin Healy, Jason H Pomerantz
{"title":"Acrylated Hyaluronic-Acid Based Hydrogel for the Treatment of Craniofacial Volumetric Muscle Loss.","authors":"Lucas Rohrer, Shinji Kato, Shane A Browne, Katharine Striedinger-Melo, Kevin Healy, Jason H Pomerantz","doi":"10.1089/ten.TEA.2023.0241","DOIUrl":"10.1089/ten.TEA.2023.0241","url":null,"abstract":"<p><p>Current treatment options for craniofacial volumetric muscle loss (VML) have disadvantages and cannot fully restore normal function. Bio-inspired semisynthetic acrylated hyaluronic acid (AcHyA) hydrogel, which fills irregularly shaped defects, resembles an extracellular matrix, and induces a minimal inflammatory response, has shown promise in experimental studies of extremity VML. We therefore sought to study AcHyA hydrogel in the treatment of craniofacial VML. For this, we used a novel model of masseter VML in the rat. Following the creation of a 5 mm × 5 mm injury to the superficial masseter and administration of AcHyA to the wound, masseters were explanted between 2 and 16 weeks postoperatively and were analyzed for evidence of muscle regeneration including fibrosis, defect size, and fiber cross-sectional area (FCSA). At 8 and 16 weeks, masseters treated with AcHyA showed significantly less fibrosis than nonrepaired controls and a smaller decrease in defect size. The mean FCSA among fibers near the defect was significantly greater among hydrogel-repaired than control masseters at 8 weeks, 12 weeks, and 16 weeks. These results show that the hydrogel mitigates the fibrotic healing response and wound contracture. Our findings also suggest that hydrogel-based treatments have potential use as a treatment for the regeneration of craniofacial VML and demonstrate a system for evaluating subsequent iterations of materials in VML injuries. Impact Statement Craniofacial volumetric muscle loss (VML) is a debilitating condition for which current treatment options are unable to restore normal appearance, or function. Tissue engineering approaches, such as hydrogel implants, may be an effective strategy to fill the volumetric defects and promote <i>de novo</i> muscle regeneration. In this study, we describe a novel rodent model for the study of craniofacial VML and a hyaluronic acid-based hydrogel that can be used as a treatment for the regeneration of craniofacial VML.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"704-711"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295406","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}