Acta Biomaterialia最新文献

{"title":"3D printed multi-coupled bioinspired skin-electronic interfaces with enhanced adhesion for monitoring and treatment","authors":"","doi":"10.1016/j.actbio.2024.08.048","DOIUrl":"10.1016/j.actbio.2024.08.048","url":null,"abstract":"<div><div>Skin-electronic interfaces have broad applications in fields such as diagnostics, therapy, health monitoring, and smart wearables. However, they face various challenges in practical use. For instance, in wet environments, the cohesion of the material may be compromised, and under dynamic conditions, maintaining conformal adhesion becomes difficult, leading to reduced sensitivity and fidelity of electrical signal transmission. The key scientific issue lies in forming a stable and tight mechanical-electronic coupling at the tissue-electronic interface. Here, inspired by octopus sucker structures and snail mucus, we propose a strategy for hydrogel skin-electronic interfaces based on multi-coupled bioinspired adhesion and introduce an ultrasound (US)-mediated interfacial toughness enhancement mechanism. Ultimately, using digital light processing micro-nano additive manufacturing technology (DLP 3D), we have developed a multifunctional, diagnostic-therapeutic integrated patch (PAMS). This patch exhibits moderate water swelling properties, a maximum deformation of up to 460%, high sensitivity (GF = 4.73), and tough and controllable bioadhesion (shear strength increased by 109.29%). Apart from outstanding mechanical and electronic properties, the patch also demonstrates good biocompatibility, anti-bacterial properties, photothermal properties, and resistance to freezing at −20 °C. Experimental results show that this skin-electronic interface can sensitively monitor temperature, motion, and electrocardiogram signals. Utilizing a rat frostbite model, we have demonstrated that this skin-electronic interface can effectively accelerate the wound healing process as a wound patch. This research offers a promising strategy for improving the performance of bioelectronic devices, sensor-based educational reforms and personalized diagnostics and therapeutics in the future.</div></div><div><h3>Statement of significance</h3><div>Establishing stable and tight mechanical-electronic coupling at the tissue-electronic interface is essential for the diverse applications of bioelectronic devices. This study aims to develop a multifunctional, diagnostic-therapeutic integrated hydrogel skin-electronic interface patch with enhanced interfacial toughness. The patch is based on a multi-coupled bioinspired adhesive-enhanced mechanism, allowing for personalized 3D printing customization. It can be used as a high-performance diagnostic-therapeutic sensor and effectively promote frostbite wound healing. We anticipate that this research will provide new insights for constructing the next generation of multifunctional integrated high-performance bioelectronic interfaces.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121303","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":"An in situ forming cartilage matrix mimetic hydrogel scavenges ROS and ameliorates osteoarthritis after superficial cartilage injury","authors":"","doi":"10.1016/j.actbio.2024.08.018","DOIUrl":"10.1016/j.actbio.2024.08.018","url":null,"abstract":"<div><div>Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including <em>in situ</em> formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. <em>In vitro</em> characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS <em>in vitro</em> and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair.</div></div><div><h3>Statement of significance</h3><div>Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047625","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":"Silk acid-tyramine hydrogels with rapid gelation properties for 3D cell culture","authors":"","doi":"10.1016/j.actbio.2024.08.027","DOIUrl":"10.1016/j.actbio.2024.08.027","url":null,"abstract":"<div><div>Silk fibroin (SF) can be enzymatically crosslinked through tyrosine residues to fabricate hydrogels with good biocompatibility and tunable mechanical properties. Using tyramine substitution can increase the phenolic group content to facilitate the gelation kinetics and mechanical properties. In this study, a two-step chemical modification method is demonstrated to synthesize silk acid-tyramine (SA-TA) conjugates with a high phenolic group content (&gt;7 mol%). The SA-TA shows rapid enzyme-catalyzed gelation property where the sol–gel transition takes less than 10 s at 37 °C, allowing cell encapsulation with uniform distribution while maintaining high cell viability (&gt;90 %). Furthermore, the enzyme-catalyzed SA-TA hydrogels show enhanced storage modulus than enzyme-catalyzed SF hydrogels, long-term stability, and good cytocompatibility, indicating their great potential in 3D cell culture. The <em>in vivo</em> implantation study demonstrates that the SA-TA hydrogels are biodegradable with a mild immune response. This implies that SA-TA hydrogels can be applied in various medical applications, such as tissue engineering, cell delivery, and 3D bioprinting.</div></div><div><h3>Statement of significance</h3><div>In this study, a two-step chemical modification method is demonstrated to synthesize silk acid-tyramine (SA-TA) conjugates with a high phenolic group content (&gt;7 mol%). Owing to the increased content of the phenolic group, the SA-TA shows rapid enzyme-catalyzed gelation property where the sol–gel transition takes less than 10 s at 37 °C, allowing cell encapsulation with uniform distribution while maintaining high cell viability (&gt;90 %). Furthermore, the enzyme-catalyzed SA-TA hydrogels show enhanced storage modulus than enzyme-catalyzed SF hydrogels, long-term stability, and good cytocompatibility, indicating their great potential in 3D cell culture. The <em>in vivo</em> implantation study demonstrates that the SA-TA hydrogels are biodegradable with a mild immune response. This implies that SA-TA hydrogels can be applied in various medical applications, such as tissue engineering, cell delivery, and 3D bioprinting.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094285","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":"Strain-dependent dynamic re-alignment of collagen fibers in skeletal muscle extracellular matrix","authors":"","doi":"10.1016/j.actbio.2024.08.035","DOIUrl":"10.1016/j.actbio.2024.08.035","url":null,"abstract":"<div><div>Collagen fiber architecture within the skeletal muscle extracellular matrix (ECM) is significant to passive muscle mechanics. While it is thought that collagen fibers re-orient themselves in response to changes in muscle length, this has not been dynamically visualized and quantified within a muscle. The goal of this study was to measure changes in collagen alignment across a range of muscle lengths and compare the corresponding alignment to muscle mechanics. We hypothesized that collagen fibers dynamically increase alignment in response to muscle stretching, and this change in alignment is related to passive muscle stiffness. Further, we hypothesized that digesting collagen fibers with collagenase would reduce the re-alignment response to muscle stretching. Using DBA/2J and D2.<em>mdx</em> mice, we isolated extensor digitorum longus (EDL), soleus, and diaphragm muscles for collagenase or sham treatment and decellularization to isolate intact or collagenase-digested decellularized muscles (DCMs). These DCMs were mechanically tested and imaged using second harmonic generation microscopy to measure collagen alignment across a range of strains. We found that collagen alignment increased in a strain-dependent fashion, but collagenase did not significantly affect the strain-dependent change in alignment. We also saw that the collagen fibers in the diaphragm epimysium (surface ECM) and perimysium (deep ECM) started at different angles, but still re-oriented in the same direction in response to stretching. These robust changes in collagen alignment were weakly related to passive DCM stiffness. Overall, we demonstrated that the architecture of muscle ECM is dynamic in response to strain and is related to passive muscle mechanics.</div></div><div><h3>Statement of significance</h3><div>Our study presents a unique visualization and quantification of strain-induced changes in muscle collagen fiber alignment as they relate to passive mechanics. Using dynamic imaging of collagen in skeletal muscle we demonstrate that as skeletal muscle is stretched, collagen fibers re-orient themselves along the axis of stretch and increase their alignment. The degree of alignment and the increase in alignment are each weakly related to passive muscle stiffness. Collagenase treatments further demonstrate that the basis for muscle Extracellular matrix stiffness is dependent on factors beyond collagen crosslinking and alignment. Together the study contributes to the knowledge of the structure-function relationships of muscle extracellular matrix to tissue stiffness relevant to conditions of fibrosis and aberrant stiffness.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115796","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":"A manganese-doped layered double hydroxide loaded with lactate oxidase and DNA repair inhibitors for synergistically enhanced tumor immunotherapy","authors":"","doi":"10.1016/j.actbio.2024.08.045","DOIUrl":"10.1016/j.actbio.2024.08.045","url":null,"abstract":"<div><div>Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn²⁺ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H₂O₂), which not only alleviates the ISME, but also provides reactants for the Mn²⁺-mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn²⁺ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis.</div></div><div><h3>Statement of significance</h3><div>To improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn²⁺ ions in the acidic tumor microenvironment. The released LOX generates H₂O₂ for the Mn²⁺-mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn²⁺ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115774","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":"Beyond bone volume: Understanding tissue-level quality in healing of maxillary vs. femoral defects","authors":"","doi":"10.1016/j.actbio.2024.08.042","DOIUrl":"10.1016/j.actbio.2024.08.042","url":null,"abstract":"<div><div>Currently, principles of tissue engineering and implantology are uniformly applied to all bone sites, disregarding inherent differences in collagen, mineral composition, and healing rates between craniofacial and long bones. These differences could potentially influence bone quality during the healing process. Evaluating bone quality during healing is crucial for understanding local mechanical properties in regeneration and implant osseointegration. However, site-specific changes in bone quality during healing remain poorly understood. In this study, we assessed newly formed bone quality in sub-critical defects in the maxilla and femur, while impairing collagen cross-linking using β-aminopropionitrile (BAPN). Our findings revealed that femoral healing bone exhibited a 73 % increase in bone volume but showed significantly greater viscoelastic and collagen changes compared to surrounding bone, leading to increased deformation during long-term loading and poorer bone quality in early healing. In contrast, the healing maxilla maintained equivalent hardness and viscoelastic constants compared to surrounding bone, with minimal new bone formation and consistent bone quality. However, BAPN-impaired collagen cross-linking induced viscoelastic changes in the healing maxilla, with no further changes observed in the femur. These results challenge the conventional belief that increased bone volume correlates with enhanced tissue-level bone quality, providing crucial insights for tissue engineering and site-specific implant strategies. The observed differences in bone quality between sites underscore the need for a nuanced approach in assessing the success of regeneration and implant designs and emphasize the importance of exploring site-specific tissue engineering interventions.</div></div><div><h3>Statement of significance</h3><div>Accurate measurement of bone quality is crucial for tissue engineering and implant therapies. Bone quality varies between craniofacial and long bones, yet it's often overlooked in the healing process. Our study is the first to comprehensively analyze bone quality during healing in both the maxilla and femur. Surprisingly, despite significant volume increase, femur healing bone had poorer quality compared to the surrounding bone. Conversely, maxilla healing bone maintained consistent quality despite minimal bone formation. Impaired collagen diminished maxillary healing bone quality, but had no further effect on femur bone quality. These findings challenge the notion that more bone volume equals better quality, offering insights for improving tissue engineering and implant strategies for different bone sites.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115775","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":"Mussel-inspired adhesive drug-loaded hydrogels for oral ulcers treatment","authors":"","doi":"10.1016/j.actbio.2024.08.038","DOIUrl":"10.1016/j.actbio.2024.08.038","url":null,"abstract":"<div><div>Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice.</div></div><div><h3>Statement of significance</h3><div>Oral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115779","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":"Polycaprolactone-based shape memory foams as self-fitting vaginal stents","authors":"","doi":"10.1016/j.actbio.2024.08.041","DOIUrl":"10.1016/j.actbio.2024.08.041","url":null,"abstract":"<div><div>There is an urgent critical need for a patient-forward vaginal stent that can prevent debilitating vaginal stenosis that occurs after pelvic radiation treatments and vaginal reconstruction. To this end, we developed a self-fitting vaginal stent based on a shape-memory polymer (SMP) foam that can assume a secondary, compressed shape for ease of deployment. Upon insertion, the change in temperature and hydration initiates foam expansion to shape fit to the individual patient and restore the lumen of the stent to allow egress of vaginal secretions. To achieve rapid actuation at physiological temperature, we investigated the effect of architecture of two photocurable, polycaprolactone (PCL) macromers. <em>Star</em>-PCL-tetraacrylate displayed a reduced melting temperature as compared to a <em>linear</em>-PCL-diacrylate. Upon fabrication into high porosity foams with emulsion-templating, both compositions displayed shape fixity (&gt;90 %) in a crimped, temporary shape. However, only the PCL <em>star-</em>foams displayed shape recovery (∼84 %) at 37 °C with expansion back to its permanent shape. A custom mold and curing system were then used to fabricate the PCL <em>star-</em>foams into hollow, cylindrical stents. The stent was crimped to its temporary insertion shape (50 % reduction in diameter, OD ∼ 11 mm) with a custom radial crimper and displayed excellent shape fixity for deployment (&gt; 95 %) and shape recovery (∼ 100 %). To screen vaginal stents, we developed a custom benchtop pelvic model that simulated vaginal anatomy, temperatures, and pressures with an associated computational model. The crimped SMP vaginal stent was deployed in the model and expanded to walls of the canal (∼70 % increase in cross-sectional area) in less than 5 min after irrigation with warm water. The vaginal stent demonstrated retention of vaginal caliber with less than 10 % decrease in cross-sectional area under physiological pressures. Collectively, this work demonstrates the potential for SMP foams as self-fitting vaginal stents to prevent stenosis and provides new open-source tools for the iterative design of other gynecological devices.</div></div><div><h3>Statement of significance</h3><div>Vaginal stenosis, a painful narrowing of the vaginal canal, is a common complication after pelvic radiation therapy or reconstructive surgery. To address this clinical need, we have created a self-fitting vaginal stent from a shape-memory polymer foam. The stent compresses for easy insertion and then expands to adapt to each patient's anatomy to maintain an open vaginal canal and prevent stenosis. This innovative stent provides a patient-friendly solution that could make a significant difference for women undergoing pelvic treatments by reducing pain, aiding recovery, and improving quality of life.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115793","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":"Collagen patches releasing phosphatidylserine liposomes guide M1-to-M2 macrophage polarization and accelerate simultaneous bone and muscle healing","authors":"","doi":"10.1016/j.actbio.2024.08.012","DOIUrl":"10.1016/j.actbio.2024.08.012","url":null,"abstract":"<div><div>Bilateral communication between bones and muscles is essential for healing composite bone–muscle injuries from orthopedic surgeries and trauma. However, these injuries are often characterized by exaggerated inflammation, which can disrupt bone–muscle crosstalk, thereby seriously delaying the healing of either tissue. Existing approaches are largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging, with little research conducted to date. Here we introduce collagen patches that overcome this overlooked issue by harnessing the plasticity of macrophage phenotypes. Phosphatidylserine liposomes (PSLs) capable of shifting the macrophage phenotype from inflammatory M1 into anti-inflammatory/prohealing M2 were coated on collagen patches via a layer-by-layer method. Original collagen patches failed to improve tissue healing under inflammatory conditions coordinated by M1 macrophages. In contrast, PSL-coated collagen patches succeeded in accelerating bone and muscle healing by inducing a microenvironment dominated by M2 macrophages. In cell experiments, differentiation of preosteoblasts and myoblasts was completely inhibited by secretions of M1 macrophages but unaffected by those of M2 macrophages. RNA-seq analysis revealed that type I interferon and interleukin-6 signaling pathways were commonly upregulated in preosteoblasts and myoblasts upon stimulation with M1 macrophage secretions, thereby compromising their differentiation. This study demonstrates the benefit of PSL-mediated M1-to-M2 macrophage polarization for simultaneous bone and muscle healing, offering a potential strategy toward simultaneous regeneration of multiple tissues.</div></div><div><h3>Statement of significance</h3><div>Existing approaches for tissue regeneration, which primarily utilize growth factors, have been largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging and has been little studied. Here we demonstrate that collagen patches releasing phosphatidylserine liposomes (PSLs) promote M1-to-M2 macrophage polarization and are effective for simultaneous healing of bone and muscle. Transcriptome analysis using next-generation sequencing reveals that differentiation of preosteoblasts and myoblasts is inhibited by the secretions of M1 macrophages but promoted by those of M2 macrophages, highlighting the importance of timely regulation of M1-to-M2 polarization in tissue regeneration. These findings provide new insight to tissue healing of multiple tissues.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006075","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":"Multi-responsive cascade enzyme-like catalytic nanoassembly for ferroptosis amplification and nanozyme-assisted mild photothermal therapy","authors":"","doi":"10.1016/j.actbio.2024.08.036","DOIUrl":"10.1016/j.actbio.2024.08.036","url":null,"abstract":"<div><div>Ferroptosis is greatly restricted by low reactive oxygen species (ROS) generation efficiency, and the inherent self-protection mechanism originating in heat shock proteins (HSPs) seriously impedes the efficiency of photothermal therapy (PTT). Herein, we designed an intelligent strategy utilizing cascade catalytic nanoassemblies (Au@COF@MnO₂) with triple-enzyme activity for amplifying ferroptosis therapy and improving the efficiency of PTT in tumor. Gold nanozyme was encapsulated within a hollow manganese dioxide (MnO₂) shell with the help of covalent organic frameworks (COFs). The nanoassemblies possess the ability of photothermal conversion. Mechanism studies suggested that glutathione (GSH) depletion by Au@COF@MnO₂ leads to the inactivation of glutathione peroxidase 4 (GPX4). This effect synergized with Mn²⁺-mediated reactive oxygen species (ROS) generation to enhance the accumulation of lipid peroxide (LPO), thereby inducing high-efficiency ferroptosis. Notably, gold nanozyme facilitated the conversion of glucose into gluconic acid and hydrogen peroxide (H₂O₂). This process augmented the endogenous H₂O₂ levels necessary for Fenton chemistry, which could effectively promote the generation of ROS. Simultaneously, glucose depletion downregulated the expression of HSPs induced by hyperthermia, consequently reducing cellular heat resistance for enhancing PTT. Therefore, the cascade catalytic nanoassembly not only exhibits high tumor inhibition and admirable biosafety, but also possesses trimodal imaging performance for imaging-guided tumor therapy <em>in vivo</em>, holding great potential for clinical application.</div></div><div><h3>Statement of significance</h3><div>This study engineered multi-responsive cascade catalytic nanoassembly (Au@COF@MnO₂) with triple enzymatic functions for amplifying ferroptosis therapy and improving the efficiency of PTT in tumor. The nanoassembly exhibited multi-responsive release and great photothermal conversion performance. Glucose consumption-evoked starvation downregulated the hyperthermia-induced expression of HSPs in tumor cells, thereby improving the efficacy of PTT. Mechanism studies suggested that GSH depletion by Au@COF@MnO₂ lead to the inactivation of GPX4, which synergized with Mn²⁺-mediated ROS generation to bolster the accumulation of LPO, thereby inducing high-efficiency ferroptosis. Moreover, the nanoassembly demonstrated trimodal (PT, PA, and MR) imaging <em>in vivo</em>, enabling the visualization of the tumor treatment with nanoassembly. Such nanoassembly exhibited high tumor inhibition and admirable biosafety in tumor therapy <em>in vivo</em>, holding a great potential for clinical application.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115778","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}