Acta Biomaterialia最新文献

{"title":"Biopolymer immune implants co-loaded with TMZ, R848 and IOX1 for perioperative therapy of glioblastoma","authors":"Pinxin Lv ,&nbsp;Zhanfeng Wang ,&nbsp;Xinghui Si ,&nbsp;Jing Su ,&nbsp;Zhifei Yu ,&nbsp;Hongquan Yu ,&nbsp;Guofeng Ji ,&nbsp;Wantong Song","doi":"10.1016/j.actbio.2024.09.053","DOIUrl":"10.1016/j.actbio.2024.09.053","url":null,"abstract":"<div><div>Glioblastoma (GBM), a prevalent and aggressive brain tumor, poses significant treatment challenges due to its rapid progression and the difficulty in achieving complete surgical resection. The current treatment regime, primarily surgery followed by radiotherapy and chemotherapy, offers limited success, with a five-year survival rate of less than 10 %. For addressing the challenges faced in the treatment of GBM, an approach using a biopolymer implant constructed with dynamic reversible covalent bonds, was designed to achieve controlled and constant-rate release of chemotherapy drug (Temozolomide, TMZ), immune adjuvant (Resiquimod, R848) and checkpoint inhibitor (5-carboxy-8-hydroxyquinoline, IOX1). The safety evaluation demonstrated the biocompatibility of the implants, with no significant inflammatory response or adverse effects on various systemic organs. <em>In vivo</em> antitumor study showed that the local delivery of drug combination via this implant significantly inhibited tumor recurrence of orthotopic GBM. Immune analysis revealed that the combination of the three drugs effectively activated systemic antitumor immune responses and induced memory effects. The synergistic mechanism of the drug combination was further validated by RNA whole sequencing. The innovative approach of combining chemotherapy and immunotherapy in biopolymer immune implants for GBM treatment showed promising and opens new avenues for treating GBM, particularly in addressing postoperative recurrence.</div></div><div><h3>Statement of significance</h3><div>Our research introduces a pioneering approach in treating orthotopic brain glioblastoma (GBM), characterized by inevitable tumor recurrence, poor immune infiltration and the restrictive nature of the blood-brain barrier. To break the impasse of ineffective treatment for GBM, the innovative use of dynamically reversible covalent bonds in polymer matrix ensures the controlled, stable and sustained release of drug combinations of the chemotherapeutic agent temozolomide, immune adjuvants and checkpoint inhibitors, which maintains the optimal concentration in the tumor, overcoming problems associated with conventional chemotherapy such as systemic toxicity and low tumor targeting. Empirical evidence from <em>in vivo</em> experiments on the rat GBM model demonstrates significant outcomes: 90 % tumor size reduction and prolonged survival with over 70 % tumor cure rate.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 143-154"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378673","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":"Revealing chemistry-structure-function relationships in shark vertebrae across length scales","authors":"Dawn Raja Somu ,&nbsp;Malena Fuentes ,&nbsp;Lihua Lou ,&nbsp;Arvind Agarwal ,&nbsp;Marianne Porter ,&nbsp;Vivian Merk","doi":"10.1016/j.actbio.2024.09.041","DOIUrl":"10.1016/j.actbio.2024.09.041","url":null,"abstract":"<div><div>Shark cartilage presents a complex material composed of collagen, proteoglycans, and bioapatite. In the present study, we explored the link between microstructure, chemical composition, and biomechanical function of shark vertebral cartilage using Polarized Light Microscopy (PLM), Atomic Force Microscopy (AFM), Confocal Raman Microspectroscopy, and Nanoindentation. Our investigation focused on vertebrae from Blacktip and Shortfin Mako sharks. As typical representatives of the orders Carcharhiniformes and Lamniformes, these species differ in preferred habitat, ecological role, and swimming style. We observed structural variations in mineral organization and collagen fiber arrangement using PLM and AFM. In both sharks, the highly calcified corpus calcarea shows a ridged morphology, while a chain-like network is present in the less mineralized intermedialia. Raman spectromicroscopy demonstrates a relative increase of glucosaminocycans (GAGs) with respect to collagen and a decrease in mineral-rich zones, underlining the role of GAGs in modulating bioapatite mineralization. Region-specific testing confirmed that intravertebral variations in mineral content and arrangement result in distinct nanomechanical properties. Local Young's moduli from mineralized regions exceeded bulk values by a factor of 10. Overall, this work provides profound insights into a flexible yet strong biocomposite, which is crucial for the extraordinary speed of cartilaginous fish in the worlds’ oceans.</div></div><div><h3>Statement of significance</h3><div>Shark cartilage is a morphologically complex material composed of collagen, sulfated proteoglycans, and calcium phosphate minerals. This study explores the link between microstructure, chemical composition, and biological mechanical function of shark vertebral cartilage at the micro- and nanometer scale in typical Carcharhiniform and Lamniform shark species, which represent different vertebral mineralization morphologies, swimming styles and speeds. By studying the intricacies of shark vertebrae, we hope to lay the foundation for biomimetic composite materials that harness lamellar reinforcement and tailored stiffness gradients, capable of dynamic and localized adjustments during movement.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 377-387"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334139","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":"Trabecular meshwork cell differentiation in response to collagen and TGFβ-2 spatial interactions","authors":"Hannah C. Lamont ,&nbsp;Abigail L. Wright ,&nbsp;Kate Devries ,&nbsp;Kerime E. Okur ,&nbsp;Michael Jones ,&nbsp;Imran Masood ,&nbsp;Lisa J. Hill ,&nbsp;Showan N. Nazhat ,&nbsp;Liam M. Grover ,&nbsp;Alicia J. El Haj ,&nbsp;Anthony D. Metcalfe","doi":"10.1016/j.actbio.2024.08.046","DOIUrl":"10.1016/j.actbio.2024.08.046","url":null,"abstract":"<div><div>Primary open-angle glaucoma (POAG) is currently the most prevalent cause of irreversible blindness globally. To date, few <em>in vitro</em> models that can faithfully recapitulate the complex architecture of the trabecular meshwork (TM) and the specialised trabecular meshwork cell (TMC) characteristics that are local to the structurally opposing regions. This study aimed to investigate the parameters that govern TMC phenotype by adapting the extracellular matrix structure to mimic the juxtacanalicular tissue (JCT) region of the TM. Initially, TMC phenotypic characteristics were investigated within type I collagen matrices of controlled fiber density and anisotropy, generated through confined plastic compression (PC). Notably, PC-collagen presented biophysical cues that induced JCT cellular characteristics (elastin, α-β-Crystallin protein expression, cytoskeletal remodelling, increased mesenchymal markers and JCT-specific genetic markers). In parallel, a pathological mesenchymal phenotype associated with POAG was induced through localised transforming growth factor -beta 2 (TGFβ-2) exposure. This resulted in a profile of alternative mesenchymal states (fibroblast/smooth muscle or myofibroblast) displayed by the TMC <em>in vitro</em>. Overall, the study provides an advanced insight into the biophysical cues that modulate TMC fate, inducing a JCT-specific phenotype and transient mesenchymal characteristics that reflect healthy and pathological scenarios.</div></div><div><h3>Statement of significance</h3><div>Glaucoma is a leading cause of blindness, with a lack of long-term efficacy within current drug candidates. Reliable trabecular meshwork (TM) <em>in vitro</em> models will be critical for enhancing the fields understanding of healthy and disease states for pre-clinical testing.</div><div>Trabecular meshwork cells (TMCs) display heterogeneity throughout the hierarchical TM, however our understanding into recapitulating these phenotypes <em>in vitro</em>, remains elusive. This study hypothesizes the importance of specific matrix/growth factor spatial stimuli in governing TMCs phenotype. By emulating certain biophysical/biochemical <em>in vivo</em> parameters, we introduce an advanced profile of distinct TMC phenotypic states, reflecting healthy and disease scenarios. A notion that has not be stated prior and a fundamental consideration for future 3D TM <em>in vitro</em> modelling.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 217-231"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115797","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":"Marc André Meyers, 2025 Acta Materialia Gold Medal Award Recipient","authors":"","doi":"10.1016/j.actbio.2024.07.050","DOIUrl":"10.1016/j.actbio.2024.07.050","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Page 672"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657331","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":"Hybrid zinc oxide nanocoating on titanium implants: Controlled drug release for enhanced antibacterial and osteogenic performance in infectious conditions","authors":"Juncen Zhou ,&nbsp;Hanbo Wang ,&nbsp;Sannakaisa Virtanen ,&nbsp;Lukasz Witek ,&nbsp;Hongzhou Dong ,&nbsp;David Thanassi ,&nbsp;Jie Shen ,&nbsp;Yunzhi Peter Yang ,&nbsp;Cunjiang Yu ,&nbsp;Donghui Zhu","doi":"10.1016/j.actbio.2024.09.039","DOIUrl":"10.1016/j.actbio.2024.09.039","url":null,"abstract":"<div><div>Implant-associated bacterial infections are a primary cause of complications in orthopedic implants, and localized drug delivery represents an effective mitigation strategy. Drawing inspiration from the morphology of desiccated soil, our group has developed an advanced drug-delivery system augmented onto titanium (Ti) plates. This system integrates zinc oxide (ZnO) nanorod arrays with a vancomycin drug layer along with a protective Poly(lactic-co-glycolic acid) (PLGA) coating. The binding between the ZnO nanorods and the drug results in attached drug blocks, isolated by desiccation-like cracks, which are then encapsulated by PLGA to enable sustained drug release. Additionally, the release of zinc ions and the generation of reactive oxygen species (ROS) from the ZnO nanorods enhance the antibacterial efficacy. The antibacterial properties of ZnO nanorod-drug-PLGA system have been validated through both <em>in vitro</em> and <em>in vivo</em> studies. Comprehensive investigations were conducted on the impact of bacterial infections on bone defect regeneration and the role of this drug-delivery system in the healing process. Furthermore, the local immune response was analyzed and the immunomodulatory function of the system was demonstrated. Overall, the findings underscore the superior performance of the ZnO nanorod-drug-PLGA system as an efficient and safe approach to combat implant-associated bacterial infections.</div></div><div><h3>Statement of significance</h3><div>Implant-associated bacterial infections pose a significant clinical challenge, particularly in orthopedic procedures. To address this, we developed an innovative ZnO nanorod-drug-PLGA system for local antibiotic delivery on conventional titanium implants. This system is biodegradable and features a unique desiccation-like structure that enables sustained drug release, along with the active substances released from the ZnO nanorods. In a rat calvarial defect model challenged with <em>S. aureus</em>, our system demonstrated remarkable antibacterial efficacy, significantly enhanced bone defect regeneration, and exhibited local immunomodulatory effects that support both infection control and osteogenesis. These breakthrough findings highlight the substantial clinical potential of this novel drug delivery system and introduce a transformative coating strategy to enhance the functionality of traditional metallic biomaterials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 589-604"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334138","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":"Vanillic acid-based pro-coagulant hemostatic shape memory polymer foams with antimicrobial properties against drug-resistant bacteria","authors":"Changling Du ,&nbsp;David Anthony Fikhman ,&nbsp;Ernest Emmanuel Obeng ,&nbsp;Sevde Nur Can ,&nbsp;Katheryn Shi Dong ,&nbsp;Eden Tess Leavitt ,&nbsp;Leo Vikram Saldanha ,&nbsp;Michaela Hall ,&nbsp;Joshua Satalin ,&nbsp;Michaela Kollisch-Singule ,&nbsp;Mary Beth B. Monroe","doi":"10.1016/j.actbio.2024.09.036","DOIUrl":"10.1016/j.actbio.2024.09.036","url":null,"abstract":"<div><div>Uncontrolled bleeding is the primary cause of trauma-related death. For patients that are brought to the hospital in time to receive treatment, there is a great risk of contracting drug-resistant bacterial wound infections. Therefore, low-cost hemostatic agents with procoagulant and antibacterial properties are essential to reduce morbidity and mortality in patients with traumatic wounds. To that end, we introduced vanillic acid (VA) into shape memory polymer (SMP) foams through a dual incorporation mechanism to make dual vanillic acid (DVA) foams. The dual mechanism increases VA loading while allowing burst and sustained delivery of VA from foams. DVA foams exhibit antimicrobial and antibiofilm properties against native and drug-resistant <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and <em>Staphylococcus epidermidis.</em> Also, DVA foams inhibit the growth rate of both methicillin-sensitive and -resistant <em>S. aureus</em> colonies to limit their size and promote small colony variants. DVA SMP foams induced primary and secondary hemostasis in <em>in vitro</em> blood interaction studies. As a proof of concept, we demonstrated easy delivery and rapid clotting in a porcine liver injury model, indicating DVA foam feasibility for use as a hemostatic dressing. Thus, the inexpensive production of DVA SMP foams could enable a cost-effective procoagulant hemostatic dressing that is resistant to bacterial colonization to improve short- and long-term outcomes for hemorrhage control in traumatically injured patients.</div></div><div><h3>Statement of significance</h3><div>Uncontrolled bleeding is the primary cause of preventable death on the battlefield. Of patients that survive, ∼40 % develop polymicrobial infections within 5 days of injury. Drug-resistant infections are anticipated to cause more deaths than all cancers combined by 2050. Therefore, novel non-drug-based biomaterials strategies for infection control in wound care are increasingly important. To that end, we developed hemostatic polyurethane foams that include antimicrobial and pro-coagulant vanillic acid, a plant-based antimicrobial species. These foams provide excellent protection against native and drug-resistant bacteria and enhanced coagulation while remaining cytocompatible. In a pilot porcine liver injury model, vanillic acid-containing foams stabilized a bleed within &lt;5 min. These biomaterials provide a promising solution for both hemorrhage and infection control in wound care.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 254-269"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334154","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 vascularized and suturable tissue constructs created through angiogenesis from tissue-engineered vascular grafts","authors":"Hazem Alkazemi ,&nbsp;Geraldine M. Mitchell ,&nbsp;Zerina Lokmic-Tomkins ,&nbsp;Daniel E. Heath ,&nbsp;Andrea J. O'Connor","doi":"10.1016/j.actbio.2024.09.052","DOIUrl":"10.1016/j.actbio.2024.09.052","url":null,"abstract":"<div><div>A major roadblock in implementing engineered tissues clinically lies in their limited vascularization. After implantation, such tissues do not integrate with the hostʼs circulation as quickly as needed, commonly resulting in loss of viability and functionality. This study presents a solution to the vascularization problem that could enable the survival and function of large, transplantable, and vascularized engineered tissues. The technique allows vascularization of a cell laden hydrogel through angiogenesis from a suturable tissue-engineered vascular graft (TEVG) constructed from electrospun polycaprolactone with macropores. The graft is surrounded by a layer of cell-laden gelatin-methacryloyl hydrogel. The constructs are suturable and possess mechanical properties like native vessels. Angiogenesis occurs through the pores in the graft, resulting in a hydrogel containing an extensive vascular network that is connected to an implantable TEVG. The size of the engineered tissue and the degree of vascularization can be increased by adding multiple TEVGs into a single construct. The engineered tissue has the potential to be immediately perfused by the patient's blood upon surgical anastomosis to host vessels, enabling survival of implanted cells. These findings provide a meaningful step to address the longstanding problem of fabricating suturable pre-vascularized tissues which could survive upon implantation <em>in vivo</em>.</div></div><div><h3>Statement of significance</h3><div>Creating vascularized engineered tissues that can be transplanted and rapidly perfused by the host blood supply is a major challenge which has limited the clinical impact of tissue engineering. In this study we demonstrate a technique to fabricate vascularized tissue constructs via angiogenesis from a suturable tissue-engineered vascular graft. The macroporous graft is surrounded with hydrogel, allowing endothelial cells to migrate from the lumen and vascularize the hydrogel layer with capillary-like structures connected to the macrovessel. The graft has comparable mechanical properties to native blood vessels and larger constructs can be fabricated by incorporating multiple grafts. These constructs could potentially be connected surgically to the circulation at an implantation site to support their immediate perfusion and survival.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 168-178"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378674","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":"Innervation in corneal bioengineering","authors":"Clare Maher ,&nbsp;Zhi Chen ,&nbsp;Ying Zhou ,&nbsp;Jingjing You ,&nbsp;Gerard Sutton ,&nbsp;Gordon Wallace","doi":"10.1016/j.actbio.2024.10.009","DOIUrl":"10.1016/j.actbio.2024.10.009","url":null,"abstract":"<div><div>Given the crucial role nerves play in maintaining corneal function and integrity, the ability of bioengineered cornea to demonstrate functional nerve regeneration directly influences their longevity and stability. Despite advances in biofabrication techniques and an increasing appreciation of the importance of neural innervation, to this day none have completely replicated the complexity and functionality of the cornea with successful innervation. This review evaluates the materials and fabrication techniques used to produce and enhance innervation in bioengineered cornea. Approaches to facilitating innervation are discussed and methods of assessing innervation compared. Finally, current challenges and future directions for innervated bioengineered cornea are presented, providing guidance for future work.</div></div><div><h3>Statement of significance</h3><div>The functional nerve regeneration in bioengineered corneas directly influences their longevity and stability. Despite advancements in biofabrication techniques and growing recognition of the importance of neural innervation for bioengineered cornea, there remains a lack of comprehensive reviews on this topic. This review addresses the critical gap by evaluating the materials and fabrication techniques employed to promote innervation in bioengineered corneas. Additionally, we discuss various approaches to enhancing innervation, compare assessment methods, and examine both <em>in vitro</em> and <em>in vivo</em> responses. By providing a comprehensive overview of the current state of research and highlighting challenges and future directions, this review aims to provide guidance for inducing innervation of bioengineered cornea.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 73-87"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407320","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":"Navigating Neurotoxicity and Safety Assessment of Nanocarriers for Brain Delivery: Strategies and Insights","authors":"Maria Inês Teixeira ,&nbsp;Carla M. Lopes ,&nbsp;Maria Helena Amaral ,&nbsp;Paulo C. Costa","doi":"10.1016/j.actbio.2024.09.027","DOIUrl":"10.1016/j.actbio.2024.09.027","url":null,"abstract":"<div><div>Nanomedicine, an area that uses nanomaterials for theragnostic purposes, is advancing rapidly, particularly in the detection and treatment of neurodegenerative diseases. The design of nanocarriers can be optimized to enhance drug bioavailability and targeting to specific organs, improving therapeutic outcomes. However, clinical translation hinges on biocompatibility and safety. Nanocarriers can cross the blood-brain barrier (BBB), potentially causing neurotoxic effects through mechanisms such as oxidative stress, DNA damage, and neuroinflammation. Concerns about their accumulation and persistence in the brain make it imperative to carry out a nanotoxicological risk assessment. Generally, this involves identifying exposure sources and routes, characterizing physicochemical properties, and conducting cytotoxicity assays both <em>in vitro</em> and <em>in vivo</em>. The lack of a specialized regulatory framework creates substantial gaps, making it challenging to translate findings across development stages. Additionally, there is a pressing need for innovative testing methods due to constraints on animal use and the demand for high-throughput screening. This review examines the mechanisms of nanocarrier-induced neurotoxicity and the challenges in risk assessment, highlighting the impact of physicochemical properties and the advantages and limitations of current neurotoxicity evaluation models. Future perspectives are also discussed. Additional guidance is crucial to improve the safety of nanomaterials and reduce associated uncertainty.</div></div><div><h3>Statement of significance</h3><div>Nanocarriers show tremendous potential for theragnostic purposes in neurological diseases, enhancing drug targeting to the brain, and improving biodistribution and pharmacokinetics. However, their neurotoxicity is still a major field to be explored, with only 5% of nanotechnology-related publications addressing this matter. This review focuses on the issue of neurotoxicity and safety assessment of nanocarriers for brain delivery. Neurotoxicity-relevant exposure sources, routes, and molecular mechanisms, along with the impact of the physicochemical properties of nanomaterials, are comprehensively described. Moreover, the different experimental models used for neurotoxicity evaluation are explored at length, including their main advantages and limitations. To conclude, we discuss current challenges and future perspectives for a better understanding of risk assessment of nanocarriers for neurobiomedical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 25-56"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303137","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":"Vaginal host response to polycarbonate urethane, an alternative material for the repair of pelvic organ prolapse","authors":"Katrina Knight ,&nbsp;Sophya Breedlove ,&nbsp;Temitope Obisesan ,&nbsp;Morgan Egnot ,&nbsp;Niusha Daneshdoost ,&nbsp;Gabrielle King ,&nbsp;Leslie Meyn ,&nbsp;Ken Gall ,&nbsp;Pamela Moalli","doi":"10.1016/j.actbio.2024.09.040","DOIUrl":"10.1016/j.actbio.2024.09.040","url":null,"abstract":"<div><div>Complications following surgical repair of pelvic organ prolapse (POP) with polypropylene mesh (PPM) are common. Recent data attributes complications, in part, to stiffness mismatches between the vagina and PPM. We developed a 3D printed elastomeric membrane (EM) from a softer polymer, polycarbonate urethane (PCU). EMs were manufactured with more material given the low inherent material strength of PCU. We hypothesized that the EMs would be associated with an improved host response as compared to PPM. A secondary goal was to optimize the material distribution (fiber width and device thickness) within EMs, in regards to the host response. EM constructs (2 × 1 cm²) with varied polymer stiffness, fiber width, and device thickness were implanted onto the vagina of New Zealand white rabbits for 12 weeks and compared to similarly sized PPMs. Sham implanted animals served as controls. Mixed effects generalized linear models were used to compare the effect of construct type accounting for differences in independent variables. EMs had an overall superior host response compared to PPM as evidenced by preservation of vaginal smooth muscle morphology (<em>p</em>-values&lt;0.01), decreased total cellular response to construct fibers (<em>p</em>-values&lt;0.001), and a reduced percent of macrophages (<em>p</em>-values&lt;0.02) independent of how the material was distributed. Both PPM and EMs negatively impacted vaginal contractility and glycosaminoglycan (GAG) content relative to Sham (all <em>p</em>-values&lt;0.001) with EMs having less of an impact on GAGs (<em>p</em>-values&lt;0.003). The results suggest that softer PCU EMs made with more material are well tolerated by the vagina and comprises a future material for POP repair devices.</div></div><div><h3>Statement of significance</h3><div>Prolapse is a debilitating condition in which loss of support to the vagina causes it and the organs supported by it to descend from their normal position in the pelvis. Surgical solutions to rebuild support involves the use of polypropylene mesh which is orders of magnitude stiffer than the vagina. This mismatch results in complications including exposure of the mesh into the vagina and pain. To provide an innovative solution for women, we have developed an elastomeric membrane from a soft polymer that matches the stiffness of the vagina. Here, we show in a rabbit animal model that this device incorporates better into the vagina and is associated with an overall improved host response as compared to polypropylene mesh.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 298-310"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373683","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}