Acta Biomaterialia最新文献

{"title":"Long range juxtacrine signalling through cadherin for collective cell orientation","authors":"Peizheng Wu,&nbsp;Shogo Sawaki,&nbsp;Kei Yamauchi,&nbsp;Kazuki Yokota,&nbsp;Masataka Hakamada,&nbsp;Mamoru Mabuchi","doi":"10.1016/j.actbio.2024.10.035","DOIUrl":"10.1016/j.actbio.2024.10.035","url":null,"abstract":"<div><div>Many life phenomena, such as development, morphogenesis, tissue remodelling, and wound healing, are often driven by orderly and directional migration of collective cells. However, when cells are randomly oriented or localized disorder exists in orderly oriented collective cells, cell migration cannot occur in an orderly manner although various motion modes such as global rotation and local swirling and/or various motion patterns such as radial pattern and chiral pattern often occur. Therefore, it is important to control cell orientation to ensure the orderly migration of collective cells. Here, we show that it is not force transmission, but juxtacrine signalling through cadherin that plays a critical role in the orientation of collective cells. Surprisingly, juxtacrine signalling for cell orientation reached cells on a plastic dish that were not directly subjected to mechanical stimulation, up to 7 mm away from the actuator. The present study suggests that even weak mechanical stimulation is transmitted in a long range without force transmission through juxtacrine signalling. The long range juxtacrine signalling might play an important role in various life phenomena.</div></div><div><h3>Statement of significance</h3><div>Juxtacrine signalling is direct cell-cell contact-dependent signalling, which plays a crucial role in cell behaviors such as mechanosensing, mechanotransduction and collective cell behaviors, however, there is not enough understanding about juxtacrine signalling. The present study has demonstrated that juxtacrine signalling for collective cell orientation is transmitted over a long range through cadherin. To the best of our knowledge, this is the first report of long range juxtacrine signalling. This finding may lead to the elucidation of various life phenomena such as development, morphogenesis, tissue remodelling, and wound healing.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 247-263"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymeric artificial heart valves derived from modified diol-based polycarbonate polyurethanes","authors":"Yage Hu,&nbsp;Yao Xiong,&nbsp;Yuan Wei,&nbsp;Jingze Liu,&nbsp;Tiantian Zheng,&nbsp;Cheng Zheng,&nbsp;Gaocan Li,&nbsp;Rifang Luo,&nbsp;Li Yang,&nbsp;Fanjun Zhang,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2024.10.045","DOIUrl":"10.1016/j.actbio.2024.10.045","url":null,"abstract":"<div><div>A series of polycarbonate silicone polyurethanes (SiPCUs) have been synthesized to develop elastomers with the mechanical properties, biostability, and biocompatibility required for artificial heart valve manufacturing. In these SiPCUs, the polar functional group 4,4′-dicyclohexylmethane diisocyanate (HMDI) was incorporated into the soft segment 1,6-poly (hexamethylene carbonate) diol (PCDL) to form the modified macromolecular diol, PCDL-HMDI-PCDL. The hard segment consisted of HMDI and the chain extenders 1,4-butanediol and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyl disiloxane (BHTD). The synthesized PHC-PCUB improves the excessive microphase separation caused by the introduction of PDMS. This material possesses good physicochemical properties, long-term oxidative degradation stability, and comparatively low mechanical performance loss after degradation. Compared to the commercially available bioprosthetic heart valve (BHV) material Glut-PP, PHC-PCUB demonstrated enhanced biocompatibility, good thromboresistant properties, less calcification, and higher endothelial cell adhesion. Furthermore, valve prototypes fabricated with PHC-PCUB showed improved hemodynamic performance under various simulated conditions, highlighting the potential of PHC-PCUB as an advanced material for valve leaflets.</div></div><div><h3>Statement of significance</h3><div>Artificial heart valves are crucial for treating valve diseases, and polyurethane-based valves present a promising alternative due to their durability, strong biocompatibility, and customizable properties. This study improves the biostability and post-degradation mechanical properties of siloxane polyurethanes by reducing the content of polydimethylsiloxane (PDMS) and adding modified diol (PCDL-HMDI-PCDL). By integrating hexamethylene diisocyanate (HMDI) and chain extenders, we developed polycarbonate siloxane polyurethanes (SiPCUs) that improve phase mixing, mechanical strength, and oxidative stability. These SiPCUs also exhibit good thromboresistance and calcification resistance, low cytotoxicity, and promote cell adhesion, positioning them as highly promising materials for heart valve leaflets, effectively addressing the limitations of current mechanical and bioprosthetic valves.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 64-78"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multifunctional cascade gas-nanoreactor with MnO2 as a gatekeeper to enhance starvation therapy and provoke antitumor immune response","authors":"Hao Ren ,&nbsp;Yunhao Bai ,&nbsp;Zhangya Liu ,&nbsp;Chenyu Ma ,&nbsp;Xinyue Tao ,&nbsp;Qiyue Wang ,&nbsp;Huibo Lian ,&nbsp;Xueming Li","doi":"10.1016/j.actbio.2024.11.004","DOIUrl":"10.1016/j.actbio.2024.11.004","url":null,"abstract":"<div><div>Glucose oxidase (GOx)-mediated starvation therapy is an effective tumor treatment that blocks energy and activates the immune response. However, the insufficient tumor immunogenicity and immunosuppressive tumor microenvironment (TME) limited its therapeutic efficacy. To address this, we have designed a multifunctional cascade gas-nanoreactor with a MnO₂ coating, which serves as an out gatekeeper to encapsulate both GOx and a carbon monoxide (CO) donor (denoted as GCM). Due to the protective effect of MnO₂ coating, GCM maintains better stability in normal physiological environments, enhancing the catalytic activity of GOx and minimizing toxic side effects. Upon accumulation in the tumor, the degradation of MnO₂ coating exposes the GOx enzyme, thereby initiating a cascade catalysis reaction to generate hydrogen peroxide (H₂O₂) and release CO in the hypoxic conditions. Additionally, the released Mn²⁺ reacts with H₂O₂ to generate toxic hydroxyl radical (•OH) as chemodynamic therapy (CDT). The synergistic treatments of starvation therapy, CO gas therapy and CDT effectively kill cancer cells and amplify immunogenic cell death (ICD), maturing DC cells and activating anti-tumor immune response. Furthermore, the released CO increases M1 macrophages infiltration and reduces myeloid-derived suppressor cells (MDSCs) infiltration, thus reversing the immunosuppressive TME. This multifunctional gas-nanoreactor provides a strategy for CO gas generation to trigger a robust anti-tumor immune response and has the potential for clinical application in cancer immunotherapy.</div></div><div><h3>Statement of significance</h3><div>A multifunctional cascade gas-nanoreactor with a MnO₂ gatekeeper was developed to perform synergistic treatments involving starvation therapy, CO gas therapy and chemodynamic therapy (CDT) for tumor elimination. The MnO₂ gatekeeper enhanced the catalytic activity of GOx within the nanoreactor by generating oxygen, thereby minimizing toxic side effects after intravenous injection. The gas-nanoreactor amplified ICD through synergistic treatments to mature DC cells and activate anti-tumor immune response. Furthermore, the released CO could reverse the immunosuppression of the TME to enhance cancer immunotherapy. The combination strategy utilizing the gas-nanoreactor demonstrates clinical potential for facilitating cancer immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 501-517"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting delivery of mifepristone to endometrial dysfunctional macrophages for endometriosis therapy","authors":"Meng Zhang ,&nbsp;Yiqing Ye ,&nbsp;Zhengyun Chen ,&nbsp;Xiaodong Wu ,&nbsp;Yue Chen ,&nbsp;Pengfei Zhao ,&nbsp;Mengdan Zhao ,&nbsp;Caihong Zheng","doi":"10.1016/j.actbio.2024.09.037","DOIUrl":"10.1016/j.actbio.2024.09.037","url":null,"abstract":"<div><div>Endometriosis seriously affects 6–10 % of reproductive women globally and poses significant clinical challenges. The process of ectopic endometrial cell colonization shares similarities with cancer, and a dysfunctional immune microenvironment, characterized by non-classically polarized macrophages, plays a critical role in the progression of endometriosis. In this study, a targeted nano delivery system (BSA@Mif NPs) was developed using bovine serum albumin (BSA) as the carrier of mifepristone. The BSA@Mif NPs were utilized to selectively target M2 macrophages highly enriched in ectopic endometrial tissue via the SPARC receptor. This targeting strategy increases drug concentration at ectopic lesions while minimizing its distribution to normal tissue, thereby reducing side effects. <em>In vitro</em> studies demonstrated that BSA@Mif NPs not only enhanced the cellular uptake of M2-type macrophages and ectopic endometrial cells but also improved the cytotoxic effect of mifepristone on ectopic endometrial cells. Furthermore, the BSA@Mif NPs effectively induced immunogenic cell death (ICD) in ectopic endometrial cells and repolarized M2-type macrophages toward the M1 phenotype, resulting in a synergistic inhibition of ectopic endometrial cell growth. <em>In vivo</em> experiments revealed that BSA@Mif NPs exhibited significant therapeutic efficacy in endometriosis-bearing mice by increasing drug accumulation in the endometriotic tissues and modulating the immune microenvironment. This targeted biomimetic delivery strategy presents a promising approach for the development of endometriosis-specific therapies based on existing drugs.</div></div><div><h3>Statement of significance</h3><div>Macrophages play an essential role in immune dysfunctional microenvironment promoting the occurrence and progression of endometriosis and can be a crucial target for developing immune microenvironment regulation strategies for the unmet long-term management of endometriosis. The albumin nanoparticles constructed based on SPARC overexpression in macrophages and endometrial cells and albumin biosafety can achieve the targeted therapy of endometriosis by increasing the passive- and active-mediated drug accumulation in ectopic endometrium and remodeling the immune microenvironment based on macrophage regulation. This study has the following implications: i) overcoming the inherent shortcomings of clinical drugs by nanotechnology is an alternative way of developing medication; ii) developing microenvironment modulation strategies based on macrophage regulation for endometriosis management is feasible.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 505-518"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of age, elastin density, and glycosaminoglycan accumulation on the delamination strength of human thoracic and abdominal aortas","authors":"Ramin Shahbad,&nbsp;Alexey Kamenskiy,&nbsp;Sayed Ahmadreza Razian,&nbsp;Majid Jadidi,&nbsp;Anastasia Desyatova","doi":"10.1016/j.actbio.2024.10.010","DOIUrl":"10.1016/j.actbio.2024.10.010","url":null,"abstract":"<div><div>Aortic dissection is a life-threatening condition caused by layer separation. Despite extensive research, the relationship between the aortic wall's structural integrity and dissection risk remains unclear. Glycosaminoglycan (GAG) accumulation and elastin loss are suspected to play significant roles. We investigated how age-related changes in aortic structure affect dissection susceptibility. Peeling tests were performed on longitudinal and circumferential thoracic (TA) and abdominal aortic (AA) strips from 35 donors aged 13–76 years (mean 38 ± 15 years, 34 % female). GAG, elastin, collagen, and smooth muscle cell (SMC) contents were assessed using bidirectional histology. Young TAs resisted longitudinal peeling better than circumferential, with delamination strengths of 65.4 mN/mm and 44.2 mN/mm, respectively. Delamination strength decreased with age in both directions, more rapidly longitudinally, equalizing at ∼20–25 mN/mm in older TAs. Delamination strength in AAs was 22 % higher than in TAs. No sex differences were observed. GAG density increased, while elastin density decreased by 2.5 % and 4 % per decade, respectively. Collagen density did not change with age, while SMC density decreased circumferentially. GAGs partially mediated the reduction in longitudinal delamination strength due to aging, while circumferential strength reduction was not mediated by changes in either GAG or elastin densities. This study explains why aortic dissections are more common in TAs, especially in older individuals, and why they typically propagate spirally. TAs exhibit lower delamination strength compared to AAs and experience strength reduction with age, a phenomenon linked to increased GAG accumulation and elastin loss. These findings enhance our understanding of the pathophysiological mechanisms behind aortic dissection.</div></div><div><h3>Statement of significance</h3><div>This work explores the age-dependent relationships between delamination strength in human aortas and wall structural content. We investigated 35 human aortas from donors aged 13 to 76 years, providing new insights into the biomechanical and histological factors that influence aortic dissection risk. Our findings elucidate how variations in elastin, glycosaminoglycan, collagen, and smooth muscle cell densities impact the structural integrity of the aorta, contributing significantly to the understanding of aortic dissection mechanisms.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 413-426"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hierarchically structured nanofibrous scaffolds spatiotemporally mediate the osteoimmune micro-environment and promote osteogenesis for periodontitis-related alveolar bone regeneration","authors":"Ze He ,&nbsp;Jia-Cheng Lv ,&nbsp;Zi-Li Zheng ,&nbsp;Cui-Ting Gao ,&nbsp;Jia-Wei Xing ,&nbsp;Bo-Lun Li ,&nbsp;Hang-Hang Liu ,&nbsp;Yao Liu ,&nbsp;Jia-Zhuang Xu ,&nbsp;Zhong-Ming Li ,&nbsp;En Luo","doi":"10.1016/j.actbio.2024.10.008","DOIUrl":"10.1016/j.actbio.2024.10.008","url":null,"abstract":"<div><div>Periodontitis suffer from inflammation-induced destruction of periodontal tissues, resulting in the serious loss of alveolar bone. Controlling inflammation and promoting bone regeneration are two crucial aspects for periodontitis-related alveolar bone defect treatment. Herein, we developed a hierarchically structured nanofibrous scaffold with a nano-embossed sheath and a bone morphogenetic protein 2-loaded core to match the periodontitis-specific features that spatiotemporally modulated the osteoimmune environment and promoted periodontal bone regeneration. We investigated the potential of this unique scaffold to treat periodontitis-related alveolar bone defects <em>in vivo</em> and <em>in vitro</em>. The results demonstrated that the hierarchically structured scaffold effectively reduced the inflammatory levels in macrophages and enhanced the osteogenic potential of bone mesenchymal stem cells in an inflammatory microenvironment. Moreover, <em>in vivo</em> experiments revealed that the hierarchically structured scaffold significantly ameliorated inflammation in the periodontium and inhibited alveolar bone resorption. Notably, the hierarchically structured scaffold also exhibited a prolonged effect on promoting alveolar bone regeneration. These findings highlight the significant therapeutic potential of hierarchically structured nanofibrous scaffolds for the treatment of periodontitis, and their promising role in the field of periodontal tissue regeneration.</div></div><div><h3>Statement of significance</h3><div>We present a novel hierarchically structured nanofibrous scaffold of coupling topological and biomolecular signals for precise spatiotemporal modulation of the osteoimmune micro-environment. Specifically, the scaffold was engineered via coaxial electrospinning of the poly(ε-caprolactone) sheath and a BMP-2/polyvinyl alcohol core, followed by surface-directed epitaxial crystallization to generate cyclic nano-lamellar embossment on the sheath. With this unique hierarchical structure, the cyclic nano-lamellar sheath provided a direct nano-topographical cue to alleviate the osteoimmune environment, and the stepwise release of BMP-2 from the core provided a biological cue for bone regeneration. This research underscores the potential of hierarchically structured nanofibrous scaffolds as a promising therapeutic approach for periodontal tissue regeneration and highlights their role in advancing periodontal tissue engineering.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 323-336"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type V collagen exhibits distinct regulatory activities in TMJ articular disc versus condylar cartilage during postnatal growth and remodeling","authors":"Prashant Chandrasekaran ,&nbsp;Abdulaziz Alanazi ,&nbsp;Bryan Kwok ,&nbsp;Qing Li ,&nbsp;Girish Viraraghavan ,&nbsp;Sriram Balasubramanian ,&nbsp;David B. Frank ,&nbsp;X. Lucas Lu ,&nbsp;David E. Birk ,&nbsp;Robert L. Mauck ,&nbsp;Nathaniel A. Dyment ,&nbsp;Eiki Koyama ,&nbsp;Lin Han","doi":"10.1016/j.actbio.2024.09.046","DOIUrl":"10.1016/j.actbio.2024.09.046","url":null,"abstract":"<div><div>Understanding matrix molecular activities that regulate the postnatal growth and remodeling of the temporomandibular joint (TMJ) articular disc and condylar cartilage will enable the development of effective regenerative strategies targeting TMJ disorders. This study elucidated the distinct roles of type V collagen (collagen V) in regulating these two units. Studying the TMJ of young adult <em>Col5a1^+/−</em> mice, we found that loss of collagen V resulted in substantial changes in the proliferation, clustering and density of progenitors in condylar cartilage, but did not have a major impact on disc cells that are more fibroblast-like. Although loss of collagen V led to thickened collagen fibrils with increased heterogeneity in the disc, there were no significant changes in local micromodulus, except for a reduction at the posterior end of the inferior side. Following the induction of aberrant occlusal loading by the unilateral anterior crossbite (UAC) procedure, both wild-type (WT) and <em>Col5a1^+/−</em> condylar cartilage exhibited salient remodeling, and <em>Col5a1^+/−</em> condyle developed more pronounced degeneration and tissue hypertrophy at the posterior end than the WT. In contrast, neither UAC nor collagen V deficiency induced marked changes in the morphology or biomechanical properties of the disc. Together, our findings highlight the distinct roles of collagen V in regulating these two units during postnatal growth and remodeling, emphasizing its more crucial role in condylar cartilage due to its impact on the highly mechanosensitive progenitors. These results provide the foundation for using collagen V to improve the regeneration of TMJ and the care of patients with TMJ disorders.</div></div><div><h3>Statement of significance</h3><div>Successful regeneration of the temporomandibular joint (TMJ) articular disc and condylar cartilage remains a significant challenge due to the limited understanding of matrix molecular activities that regulate the formation and remodeling of these tissues. This study demonstrates that collagen V plays distinct and critical roles in these processes. In condylar cartilage, collagen V is essential for regulating progenitor cell fate and maintaining matrix integrity. In the disc, collagen V also regulates fibril structure and local micromechanics, but has a limited impact on cell phenotype or its remodeling response. Our findings establish collagen V as a key component in maintaining the integrity of these two units, with a more crucial role in condylar cartilage due to its impact on progenitor cell activities.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 192-207"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosting chondrocyte bioactivity with ultra-sulfated glycopeptide supramolecular polymers","authors":"Christopher H. Sollenberger ,&nbsp;Ruomeng Qiu ,&nbsp;Hiroaki Sai ,&nbsp;James K. Carrow ,&nbsp;Timmy Fyrner ,&nbsp;Zijun Gao ,&nbsp;Liam C. Palmer ,&nbsp;Samuel I. Stupp","doi":"10.1016/j.actbio.2024.09.047","DOIUrl":"10.1016/j.actbio.2024.09.047","url":null,"abstract":"<div><div>Although autologous chondrocyte transplantation can be effective in articular cartilage repair, negative side effects limit the utility of the treatment, such as long recovery times, poor engraftment or chondrogenic dedifferentiation, and cell leakage. Peptide-based supramolecular polymers have emerged as promising bioactive systems to promote tissue regeneration through cell signaling and dynamic behavior. We report here on the development of a series of glycopeptide amphiphile supramolecular nanofibers with chondrogenic bioactivity. These supramolecular polymers were found to have the ability to boost TGFβ-1 signaling by displaying galactosamine moieties with differing degrees of sulfation on their surfaces. We were also able to encapsulate chondrocytes with these nanostructures as single cells without affecting viability and proliferation. Among the monomers tested, assemblies of trisulfated glycopeptides led to elevated expression of chondrogenic markers relative to those with lower degrees of sulfation that mimic chondroitin sulfate repeating units. We hypothesize the enhanced bioactivity is rooted in specific interactions of the supramolecular assemblies with TGFβ-1 and its consequence on cell signaling, which may involve elevated levels of supramolecular motion as a result of high charge in trisulfated glycopeptide amphiphiles. Our findings suggest that supramolecular polymers formed by the ultra-sulfated glycopeptide amphiphiles could provide better outcomes in chondrocyte transplantation therapies for cartilage regeneration.</div></div><div><h3>Statement of significance</h3><div>This study prepares glycopeptide amphiphiles conjugated at their termini with chondroitin sulfate mimetic residues with varying degrees of sulfation that self-assemble into supramolecular nanofibers in aqueous solution. These supramolecular polymers encapsulate chondrocytes as single cells through intimate contact with cell surface structures, forming artificial matrix that can localize the growth factor TGFβ-1 in the intercellular environment. A high degree of sulfation on the glycopeptide amphiphile is found to be critical in elevating chondrogenic cellular responses that supersede the efficacy of natural chondroitin sulfate. This work demonstrates that supramolecular assembly of a unique molecular structure designed to mimic chondroitin sulfate successfully boosts chondrocyte bioactivity by single cell encapsulation, suggesting a new avenue implementing chondrocyte transplantation with supramolecular nanomaterials for cartilage regeneration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 103-115"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuning a bioengineered hydrogel for studying astrocyte reactivity in glioblastoma","authors":"Thomas J. DePalma ,&nbsp;Colin L. Hisey ,&nbsp;Kennedy Hughes ,&nbsp;David Fraas ,&nbsp;Marie Tawfik ,&nbsp;Jason Scharenberg ,&nbsp;Sydney Wiggins ,&nbsp;Kim Truc Nguyen ,&nbsp;Derek J. Hansford ,&nbsp;Eduardo Reátegui ,&nbsp;Aleksander Skardal","doi":"10.1016/j.actbio.2024.09.048","DOIUrl":"10.1016/j.actbio.2024.09.048","url":null,"abstract":"<div><div>Astrocytes play many essential roles in the central nervous system (CNS) and are altered significantly in disease. These reactive astrocytes contribute to neuroinflammation and disease progression in many pathologies, including glioblastoma (GB), an aggressive form of brain cancer. Current <em>in vitro</em> platforms do not allow for accurate modeling of reactive astrocytes. In this study, we sought to engineer a simple bioengineered hydrogel platform that would support the growth of primary human astrocytes and allow for accurate analysis of various reactive states. After validating this platform using morphological analysis and qPCR, we then used the platform to begin investigating how astrocytes respond to GB derived extracellular vesicles (EVs) and soluble factors (SF). These studies reveal that EVs and SFs induce distinct astrocytic states. In future studies, this platform can be used to study how astrocytes transform the tumor microenvironment in GB and other diseases of the CNS.</div></div><div><h3>Statement of significance</h3><div>Recent work has shown that astrocytes help maintain brain homeostasis and may contribute to disease progression in diseases such as glioblastoma (GB), a deadly primary brain cancer. <em>In vitro</em> models allow researchers to study basic mechanisms of astrocyte biology in healthy and diseased conditions, however current <em>in vitro</em> systems do not accurately mimic the native brain microenvironment. In this study, we show that our hydrogel system supports primary human astrocyte culture with an accurate phenotype and allows us to study how astrocytes change in response to a variety of inflammatory signals in GB. This platform could be used further investigate astrocyte behavior and possible therapeutics that target reactive astrocytes in GB and other brain diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 155-167"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A biodegradable shape memory polyurethane film as a postoperative anti-adhesion barrier for minimally invasive surgery","authors":"Xiwan Wang ,&nbsp;Febyana Noor Fadlilah ,&nbsp;Qian Yang ,&nbsp;Yawen Hong ,&nbsp;Di Wu ,&nbsp;Min Peng ,&nbsp;Xingjie Peng ,&nbsp;Jinchuan Wu ,&nbsp;Yanfeng Luo","doi":"10.1016/j.actbio.2024.09.018","DOIUrl":"10.1016/j.actbio.2024.09.018","url":null,"abstract":"<div><div>Postoperative adhesions commonly form in various tissues, resulting in serious implications and an increased risk of secondary surgery. The application of anti-adhesion films as physical barriers has proven effective in reducing adhesion incidence and severity. However, existing anti-adhesion films require manual deployment during minimally invasive surgery, posing inconvenience and possibility of further injury. To address these limitations, we have developed an intelligent anti-adhesion film based on shape memory polyurethane. In this work, a linear shape memory polyurethane (ISO2-PU), incorporating hexamethylene isocyanate and isosorbitol as hard segments and poly(D, L-lactic acid) macrodiol as soft segments, was fabricated into an anti-adhesion film. The favorable shape memory effect of the ISO2-PU film ensures its convenient delivery and automatic unfolding, as revealed by a simulation experiment for endoscopic surgical implantation. Furthermore, the glass transition temperature (<em>T</em>_g) close to body temperature endows the ISO2-PU film with good mechanical compliance, thus ensuring a reliable fit with the wounded tissue to avoid undesired folding. Finally, <em>in vivo</em> experiments using a rat cecal abdominal wall injury model demonstrated that the combination of reliable fit, appropriate degradation rate, and good cytocompatibility promises the ISO2-PU film with high anti-adhesion efficacy. This work validates the concept of shape memory anti-adhesion barrier and expands future directions for advanced anti-adhesion biomaterials.</div></div><div><h3>Statement of significance</h3><div>Postoperative adhesions are a common complication that occurs widely after various surgeries. This work developed an intelligent anti-adhesion film based on a linear shape memory polyurethane (ISO2-PU). This film is featured with remarkable shape memory effect and mechanical compliance at body temperature, appropriate degradability, and good cytocompatibility. These merits ensure convenient delivery and smart unfolding of ISO2-PU film during minimally invasive surgery and favorable postoperative anti-adhesion efficacy. The results validate the concept of shape memory anti-adhesion barrier and paves a way for designing next-generation anti-adhesion biomaterials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 311-322"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}