Acta Biomaterialia最新文献

{"title":"Fibrinogen αC-region acts as a functional safety latch: Implications for a fibrin biomechanical behaviour model","authors":"Tímea Feller ,&nbsp;Helen R. McPherson ,&nbsp;Simon D. Connell ,&nbsp;Robert A.S. Ariëns","doi":"10.1016/j.actbio.2024.10.005","DOIUrl":"10.1016/j.actbio.2024.10.005","url":null,"abstract":"<div><div>Fibrin has unique biomechanical properties which are essential for its role as a scaffold for blood clots. Fibrin is highly extensible and demonstrates significant strain stiffening behaviour, which is essential for stress-distribution in the network. Yet the exact structures of fibrin at the sub-fibre level that contribute to its unique biomechanical characteristic are unknown. Here we show how truncations of the fibrinogen αC-region impact the biomechanical properties of fibrin fibres. Surprisingly, absence of the complete αC-region did not influence the low strain modulus of fibrin fibres but led to premature fibre rupture and decreased extensibility. Intermediate effects were observed with partial deletion of the αC-region, reflected by intermediate rupture stress and toughness. However, overall strain-stiffening behaviour remained even in absence of the αC-region, indicating that strain stiffening is not due to stress being transferred from the αC-region to the protofibril backbone. Upon stress-relaxation, decay constants and their relative contribution to the total relaxation remained similar at all strains, showing that a distinct relaxation process is present until fibre rupture. However, relative contribution of fast relaxation was maximal only in crosslinked fibres if the flexible αC-connector was present. These data show that the αC-region is not the main load-bearing structure within fibrin fibres and point to a critical role for the protofibril backbone instead. We present a revised structural model based on protofibril branching that fully explains the unique biomechanical behaviour of fibrin fibres, while the αC-region primarily acts as a safety latch at the highest of strains.</div></div><div><h3>Statement of significance</h3><div>The findings presented in this paper reveal critically important details about how the molecular structure of fibrin contributes to its unique mechanical properties which are essential to fulfil its function as the scaffold of blood clots. In this work we used engineered proteins with alterations in an important but highly disordered area of the molecule called αC-region and we provide direct evidence for the first time for how the absence of either the globular αC-domain, or the complete αC-region impacts the mechanical behaviour of individual fibrin fibres. Using these results we developed a new structural model of protofibril organisation within fibrin fibres that fully explains their strain stiffening, relatively low modulus and their high, largely variable, extensibility.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 179-191"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407319","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":"Elizabeth Cosgriff-Hernández, 2025 Acta Materialia Mary Fortune Global Diversity Medal Recipient","authors":"","doi":"10.1016/j.actbio.2024.07.047","DOIUrl":"10.1016/j.actbio.2024.07.047","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 668-669"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657328","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":"Polyphenol-modified biomimetic bioadhesives for the therapy of annulus fibrosus defect and nucleus pulposus degeneration after discectomy","authors":"Yan Ju ,&nbsp;Shiyuan Ma ,&nbsp;Meimei Fu ,&nbsp;Min Wu ,&nbsp;Yue Li ,&nbsp;Yue Wang ,&nbsp;Meihan Tao ,&nbsp;Zhihui Lu ,&nbsp;Jinshan Guo","doi":"10.1016/j.actbio.2024.09.038","DOIUrl":"10.1016/j.actbio.2024.09.038","url":null,"abstract":"<div><div>Discectomy is the surgical standard of care to relieve low back pain caused by intervertebral disc (IVD) herniation. However, there remains annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration, which often result in recurrent herniation (re-herniation). Herein, we develop a polyphenol-modified waterborne polyurethane bioadhesives (PPU-glues) to promote therapy prognosis after discectomy. Being composed of tannic acid (TA) mixed cationic waterborne polyurethane nanodispersions (TA/WPU⁺) and curcumin (Cur) embedded anionic waterborne polyurethane nanodispersions (Cur-WPU^-), PPU-glue gels rapidly (&lt;10 s) and exhibits low swelling ratios, tunable degradation rates and good biocompatibility. Due to the application of an adhesion strategy combing English ivy mechanism and particle packing theory, PPU-glue also shows considerable lap shear strength against wet porcine skin (≈58 kPa) and burst pressure (≈26 kPa). The mismatched particle sizes and the opposite charges of TA/WPU⁺ and Cur-WPU^- in PPU-glue bring electrostatic interaction and enhance particle packing density. PPU-glue possesses superior reactive oxygen species (ROS)-scavenging capacity derived from polyphenols. PPU-glue can regulate extracellular matrix (ECM) metabolism in degenerated NP cells, and it can promote therapy biologically and mechanically in degenerated rat caudal discs. In summary, this study highlights the therapeutic approach that combines AF seal and NP augmentation, and PPU-glue holds great application potentials for post discectomy therapy.</div></div><div><h3>Statement of significance</h3><div>Currently, there is no established method for the therapy of annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration after discectomy. Herein, we developed a polyphenol-modified biomimetic polyurethane bioadhesive (PPU-glue) with strong adhesive strength and superior bioactive property. The adhesion strategy that combined a particle packing theory and an English ivy mechanism was firstly applied to the intervertebral disc repair field, which benefited AF seal. The modified method of incorporating polyphenols was utilized to confer with ROS-scavenging capacity, ECM metabolism regulation ability and anti-inflammatory property, which promoted NP augmentation. Thus, PPU-glue attained the synergy effect for post discectomy therapy, and the design principle could be universally expanded to the bioadhesives for other surgical uses.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 116-129"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373681","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":"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}