Acta Biomaterialia最新文献

{"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}

{"title":"Mitigating adverse effects of Cu-containing intrauterine devices using a highly biocompatible Cu5Fe alloy","authors":"Lijun Yang ,&nbsp;Guo Bao ,&nbsp;Cancan Yao ,&nbsp;Tian Diao ,&nbsp;Zhenning Su ,&nbsp;Tingting Liu ,&nbsp;Guannan Li ,&nbsp;Gonglei Wang ,&nbsp;Xihua Chen ,&nbsp;Xiangbo Xu ,&nbsp;Bing Sun ,&nbsp;Xiaoxue Xu ,&nbsp;Bin He ,&nbsp;Yufeng Zheng","doi":"10.1016/j.actbio.2024.09.022","DOIUrl":"10.1016/j.actbio.2024.09.022","url":null,"abstract":"<div><div>Copper-containing intrauterine devices (Cu-IUD) are adopted by worldwide women for contraception with the advantages of long-term effectiveness, reversibility and affordability. However, adverse effects occur in the initial implantation stage of Cu-IUD in uterine because of the burst release of Cu²⁺. To minimize the burst release, in this study, we designed a series of Cu–Fe alloys with 0.5 wt%, 1 wt% and 5 wt% Fe and also further produced ultrafine grained (UFG) structure for these alloys via equal-channel angular pressing. The microstructures and properties of the coarse grained (CG) Cu, CG Cu–Fe alloys and UFG Cu–Fe alloys were systematically investigated, including grain structure and phase compositions, metallic ions release behavior, electrochemical corrosion performance, and <em>in vitro</em> cytotoxicity. With careful comparison and selection, we chose the CG Cu–5Fe and UFG Cu–5Fe for <em>in vivo</em> tests using rat model, including tissue biocompatibility, <em>in vivo</em> corrosion behavior, and contraceptive effectiveness. Moreover, the corrosion mechanism of the Cu–5Fe alloy and its improved biocompatibility was discussed. Both CG and UFG Cu–5Fe alloys exhibited dramatic suppression of Cu²⁺ release in simulated uterine fluid for the long-term immersion process. The <em>in vivo</em> tissue compatibility was significantly improved with both CG and UFG Cu–5Fe alloys implanted in the rats’ uterine while the high contraceptive efficacy was well maintained. Due to the superior biocompatibility, the CG and UFG Cu–5Fe alloys can be the promising candidate material for Cu-IUD.</div></div><div><h3>Statement of significance</h3><div>A highly biocompatible Cu–Fe alloy was designed and fabricated for Cu-containing intrauterine devices (Cu-IUD). With 5 wt% Fe, the burst release of Cu²⁺ is inhibited due to the formed galvanic cell of Cu and Fe, resulting in earlier release of Fe³⁺. As Fe is the most abundant essential trace element of human body, it can mitigate the toxic effects of Cu²⁺, thus significantly improving both <em>in vitro</em> cell compatibility and <em>in vivo</em> tissue compatibility. More importantly, the Cu–5Fe alloy exhibits 100 % contraceptive efficiency as the CG Cu, but with greatly reduced adverse effects to the uterus tissues. An advanced Cu-IUD can be developed using Cu–Fe alloys.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 651-667"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373748","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":"An optical system for cellular mechanostimulation in 3D hydrogels","authors":"Rahul Sreedasyam ,&nbsp;Bryce G. Wilson ,&nbsp;Patricia R. Ferrandez ,&nbsp;Elliot L. Botvinick ,&nbsp;Vasan Venugopalan","doi":"10.1016/j.actbio.2024.09.050","DOIUrl":"10.1016/j.actbio.2024.09.050","url":null,"abstract":"<div><div>We introduce a method utilizing single laser-generated cavitation bubbles to stimulate cellular mechanotransduction in dermal fibroblasts embedded within 3D hydrogels. We demonstrate that fibroblasts embedded in either amorphous or fibrillar hydrogels engage in Ca²⁺ signaling following exposure to an impulsive mechanical stimulus provided by a single 250 µm diameter laser-generated cavitation bubble. We find that the spatial extent of the cellular signaling is larger for cells embedded within a fibrous collagen hydrogel as compared to those embedded within an amorphous polyvinyl alcohol polymer (SLO-PVA) hydrogel. Additionally, for fibroblasts embedded in collagen, we find an increased range of cellular mechanosensitivity for cells that are polarized relative to the radial axis as compared to the circumferential axis. By contrast, fibroblasts embedded within SLO-PVA did not display orientation-dependent mechanosensitivity. Fibroblasts embedded in hydrogels and cultured in calcium-free media did not show cavitation-induced mechanotransduction; implicating calcium signaling based on transmembrane Ca²⁺ transport. This study demonstrates the utility of single laser-generated cavitation bubbles to provide local non-invasive impulsive mechanical stimuli within 3D hydrogel tissue models with concurrent imaging using optical microscopy.</div></div><div><h3>Statement of significance</h3><div>Currently, there are limited methods for the non-invasive real-time assessment of cellular sensitivity to mechanical stimuli within 3D tissue scaffolds. We describe an original approach that utilizes a pulsed laser microbeam within a standard laser scanning microscope system to generate single cavitation bubbles to provide impulsive mechanostimulation to cells within 3D fibrillar and amorphous hydrogels. Using this technique, we measure the cellular mechanosensitivity of primary human dermal fibroblasts embedded in amorphous and fibrillar hydrogels, thereby providing a useful method to examine cellular mechanotransduction in 3D biomaterials. Moreover, the implementation of our method within a standard optical microscope makes it suitable for broad adoption by cellular mechanotransduction researchers and opens the possibility of high-throughput evaluation of biomaterials with respect to cellular mechanosignaling.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 439-448"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378671","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":"Versatile self-assembled near-infrared SERS nanoprobes for multidrug-resistant bacterial infection-specific surveillance and therapy","authors":"Qian Gao ,&nbsp;Ruocan Liu ,&nbsp;Yundi Wu ,&nbsp;Fuxiang Wang ,&nbsp;Xilong Wu","doi":"10.1016/j.actbio.2024.09.054","DOIUrl":"10.1016/j.actbio.2024.09.054","url":null,"abstract":"<div><div>The rise of multidrug-resistant bacteria (MDRB) has made bacterial infection one of the biggest health threats, causing numerous antibiotics to fail. Real-time monitoring of bacterial disease treatment efficacy at the infection site is required. Herein, we report a versatile Raman tag 3,3′-diethylthiatricarbocyanine iodide (DTTC)-conjugated star-shaped Au-MoS₂@hyaluronic acid (AMD@HA) nanocomposite as a surface-enhanced Raman scattering (SERS) nanoprobe for quick bacterial identification and in-situ eradication. Localized surface plasmon resonance (LSPR) from the hybrid metallic nanostructure makes AMD@HA highly responsive to the near-infrared laser, enabling it to demonstrate a photothermal (PTT) effect, increased SERS activity, and peroxidase-like catalytic reaction to release reactive oxygen species. The tail vein injection of AMD@HA nanoprobes is invasive, however SERS imaging for bacterial identification is non-invasive and sensitive, making it an efficient residual bacteria monitoring method. The detection limit for methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) is as low as 10² CFU·mL^-1, and the substrates allow for taking 120 s to acquire a Raman image of 1600 (40 × 40) pixels. In mouse models of MRSA-induced wound infection and skin abscess, the combination of AMD@HA-mediated PTT and catalytic therapy demonstrates a synergistic effect in promoting wound healing through rapid sterilization. This SERS-guided therapeutic approach exhibits little toxicity and does not cause considerable collateral damage, offering a highly promising intervention for treating diseases caused by MDRB.</div></div><div><h3>Statement of significance</h3><div>This research introduces a SERS nanoprobe, AMD@HA, for the rapid identification and eradication of multidrug-resistant bacteria (MDRB), a critical health threat. The nanoprobe leverages localized surface plasmon resonance for photothermal therapy and enhanced Raman signals, offering a sensitive, non-invasive diagnostic tool. With a low detection limit for MRSA and a synergistic therapeutic effect in mouse models, our approach holds significant promise for treating MDRB-driven infections with minimal toxicity, advancing the field of antimicrobial strategies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 559-573"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382712","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}