Acta Biomaterialia最新文献

{"title":"Plasticity variable collagen-PEG interpenetrating networks modulate cell spreading","authors":"","doi":"10.1016/j.actbio.2024.08.040","DOIUrl":"10.1016/j.actbio.2024.08.040","url":null,"abstract":"<div><div>The extracellular matrix protein collagen I has been used extensively in the field of biomaterials due to its inherent biocompatibility and unique viscoelastic and mechanical properties. Collagen I self-assembly into fibers and networks is environmentally sensitive to gelation conditions such as temperature, resulting in gels with distinct network architectures and mechanical properties. Despite this, collagen gels are not suitable for many applications given their relatively low storage modulus. We have prepared collagen-poly(ethylene glycol) [PEG] interpenetrating network (IPN) hydrogels to reinforce the collagen network, which also induces changes to network plasticity, a recent focus of study in cell-matrix interactions. Here, we prepare collagen/PEG IPNs, varying collagen concentration and collagen gelation temperature to assess changes in microarchitecture and mechanical properties of these networks. By tuning these parameters, IPNs with a range of stiffness, plasticity and pore size are obtained. Cell studies suggest that matrix plasticity is a key determinant of cell behavior, including cell elongation, on these gels. This work presents a natural/synthetic biocompatible matrix that retains the unique structural properties of collagen networks with increased storage modulus and tunable plasticity. The described IPN materials will be of use for applications in which control of cell spreading is desirable, as only minimal changes in sample preparation lead to changes in cell spreading and circularity. Additionally, this study contributes to our understanding of the connection between collagen self-assembly conditions and matrix structural and mechanical properties and presents them as useful tools for the design of other collagen based biomaterials.</div></div><div><h3>Statement of significance</h3><div>We developed a collagen-poly(ethylene glycol) interpenetrating network (IPN) platform that retains native collagen architecture and biocompatibility but provides higher stiffness and tunable plasticity. With minor changes in collagen gelation temperature or concentration, IPN gels with a range of plasticity, storage modulus, and pore size can be obtained. The tunable plasticity of the gels is shown to modulate cell spreading, with a greater proportion of elongated cells on the most plastic of IPNs, supporting the assertion that matrix plasticity is a key determinant of cell spreading. The material can be of use for situations where control of cell spreading is desired with minimal intervention, and the findings herein may be used to develop similar collagen based IPN platforms.</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":"142115792","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":"Spatially confined photoacoustic effects of responsive nanoassembly boosts lysosomal membrane permeabilization and immunotherapy of triple-negative breast cancer","authors":"","doi":"10.1016/j.actbio.2024.08.021","DOIUrl":"10.1016/j.actbio.2024.08.021","url":null,"abstract":"<div><div>Although immunogenic cell death (ICD) induced by lysosomal membrane permeabilization (LMP) evidently enhance the effectiveness of antitumor immunity for triple-negative breast cancer (TNBC) with poor immunogenicity, their potential is increasingly restricted by the development of other death pathways and the repair of lysosomes by endoplasmic reticulum (ER) during LMP induction. Herein, a polydopamine nanocomposite with i-motif DNA modified and BNN6 loaded is prepared toward boosting LMP and immunotherapy of TNBC by synergy of spatially confined photoacoustic (PA) effects and nitric oxide. Combining the high-frequency pulsed laser (4000 kHz) with the intra-lysosomal assembly of nanocomposites produced spatially confined and significantly boosted PA effects (4.8-fold higher than the individually dispersed particles extracellular), suppressing damage to other cellular components and selectively reducing lysosomal integrity to 19.2 %. Simultaneously, the releasing of nitric oxide inhibited the repair of lysosomes by ER stress, causing exacerbated LMP. Consequently, efficient immune activation was achieved, including the abundant releasing of CRT/HMGB1 (5.93–6.8-fold), the increasing maturation of dendritic cells (3.41-fold), and the fostered recruitment of CD4⁺/CD8⁺ <em>T</em> cells (3.99–3.78-fold) <em>in vivo</em>. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors.</div></div><div><h3>Statement of significance</h3><div>A strategy of boosting lysosomal membrane permeabilization (LMP) and concomitantly preventing the repair was developed to address the immunotherapy challenge of triple-negative breast cancer. Spatially confined and significantly enhanced photoacoustic (PA) effects were achieved through DNA-guided pH-responsive assembly of polydopamine nanocomposites in lysosomes and application of a high-frequency pulsed laser. Efficient immunogenic cell death was guaranteed by selective and powerful damage of lysosomal membranes through the significant contrast of PA intensities for dispersed/assembled particles and nitric oxide release induced endoplasmic reticulum stress. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors.</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":"142115794","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":"Facile fabrications of poly (acrylic acid)-mesoporous zinc phosphate/polydopamine Janus nanoparticles as a biosafe photothermal therapy agent and a pH/NIR-responsive drug carrier","authors":"","doi":"10.1016/j.actbio.2024.08.020","DOIUrl":"10.1016/j.actbio.2024.08.020","url":null,"abstract":"<div><div>Balancing biocompatibility and drug-loading efficiency in nanoparticles presents a significant challenge. In this study, we describe the facile fabrication of poly (acrylic acid)-mesoporous zinc phosphate/polydopamine (PAA-mZnP/PDA) Janus nanoparticles (JNPs). The PDA half-shell itself can serve as a photothermal agent for photothermal therapy (PTT), as well as to offers sites for polyethylene glycol (PEG) to enhance biocompatibility. Concurrently, the mesoporous ZnP core allows high loading of doxorubicin (DOX) for chemotherapy and the Cy5.5 dye for fluorescence imaging. The resultant PAA-mZnP/PDA-PEG JNPs exhibit exceptional biocompatibility, efficient drug loading (0.5 mg DOX/1 mg JNPs), and dual pH/NIR-responsive drug release properties. We demonstrate the JNPs’ satisfactory anti-cancer efficacy, highlighting the synergistic effects of chemotherapy and PTT. Furthermore, the potential for synergistic fluorescence imaging-guided chemo-phototherapy in cancer treatment is illustrated. Thus, this work exemplifies the development of biosafe, multifunctional JNPs for advanced applications in cancer theranostics.</div></div><div><h3>Statement of significance</h3><div>Facile fabrication of monodispersed nanomedicine with multi-cancer killing modalities organically integrated is nontrivial and becomes more challenging under the biocompatibility requirement that is necessary for the practical applications of nanomedicines. In this study, we creatively designed PAA-mZnP/PDA JNPs and fabricated them under mild conditions. Our method reliably yields uniform JNPs with excellent monodispersity. To maximize functionalities, we achieve fourfold advantages including efficient drug/fluorescent dye loading, PTT, pH/NIR dual-responsive properties, and optimal biocompatibility. The as-fabricated JNPs exhibit satisfactory anti-cancer performance both <em>in vitro</em> and <em>in vivo</em>, and demonstrate the potential of JNPs in fluorescence imaging-guided synergistic cancer chemo-phototherapy. Overall, our research establishes a pathway in versatile inorganic/polymer JNPs for enhanced cancer diagnosis and therapy.</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":"142047626","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":"Micron-scale topographies affect phagocytosis of bacterial cells on polydimethylsiloxane surfaces","authors":"","doi":"10.1016/j.actbio.2024.08.043","DOIUrl":"10.1016/j.actbio.2024.08.043","url":null,"abstract":"<div><div>Many medical devices implanted in patients to mitigate diseases and medical conditions have different types of topographic features. While appropriate textures can promote the integration of host cells and reduce scar tissue formation, some textured implants with inappropriate topographies have been associated with inflammation, bacterial colonization, or even malignant complications. To better understand how surface topography affects host immune response to colonizing bacteria, a protocol was developed to investigate phagocytosis of bacterial cells attached on polydimethylsiloxane (PDMS) surfaces with different square-shaped recessive patterns. The interaction between activated RAW 264.7 macrophages and <em>Escherichia coli</em> in recessive wells was visualized in 3D using multiple fluorescent markers. The results revealed that there is a threshold dimension of topography, below which phagocytosis of attached bacterial cells is significantly impeded. Specifically, under our experimental condition, up to 100-fold reduction in phagocytosis was observed in square-shaped patterns with 5 µm side length and 10 µm depth compared to the flat control and patterns with 10 µm or longer side length. The spacing between wells also showed significant effects; e.g., phagocytosis in the wells further decreased when spacing increased to 50 µm. These results are helpful for understanding how undesired topographies may contribute to bacterial colonization and thus infection and other associated complications.</div></div><div><h3>Statement of significance</h3><div>Surface topography plays an important role in bacteria-material infections and thus the safety of implantable medical devices. Undesired topographic features can cause biofilm formation and related complications. However, how surface topography affects the capability of host immune cells to clear colonizing bacteria is not well understood. In this study, the interaction between macrophage RAW264.7 and colonizing <em>E. coli</em> cells on polydimethylsiloxane (PDMS) with recessive features is investigated. It was discovered that the size of recessive features and the spacing between these features have significant effects on phagocytosis of bacteria by macrophages. These new results are helpful for understanding the complex interaction among host cells, bacteria, and implanted biomaterials, which will help guide the rational design of safer medical devices.</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":"142115777","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":"Effective treatment of traumatic brain injury by injection of a selenium-containing ointment","authors":"","doi":"10.1016/j.actbio.2024.08.051","DOIUrl":"10.1016/j.actbio.2024.08.051","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is an incurable and overwhelming disease accompanied with serve disability and huge financial burden, where the overproduced reactive oxygen species (ROS) can exacerbate the secondary injury, leading to massive apoptosis of neurons. In this study, β-cyclodextrin (CD)-capped hyperbranched polymers containing selenium element (HSE-CD) were crosslinked with CD-modified hyaluronic acid (HA-CD) and amantadine-modified hyaluronic acid (HA-AD) to obtain a ROS-responsive ointment (R-O). The structures of synthesized polymers were characterized with ¹H nuclear magnetic resonance, and the properties of ointment were investigated with rheology and antioxidation. Compared to non-ROS-responsive ointment (N-O), the R-O ointment had stronger efficiency in decreasing the ROS level in BV2 cells <em>in vitro</em>. In a controlled rat cortical impact (CCI) model, the R-O ointment could relieve the DNA damage and decrease apoptosis in injured area via reducing the ROS level. Besides, after the R-O treatment, the rats showed significantly less activated astrocytes and microglia, a lower level of pro-inflammatory cytokines and a higher ratio of M2/M1 macrophage and microglia. Moreover, compared to the TBI group the R-O ointment promoted the doublecortin (DCX) expression and tissue structure integrity around the cavity, and promoted the recovery of nerve function post TBI.</div></div><div><h3>Statement of significance</h3><div>Traumatic brain injury (TBI) is an incurable and overwhelming disease, leading to severe disability and huge social burden, where reactive oxygen species (ROS) are considered as one of the most significant factors in the secondary injury of TBI. A ROS responsive supramolecular ointment containing di-selenide bonds was injected in rats with controlled cortical impact. It relieved the DNA damage and decreased apoptosis in the injured area via reducing the ROS levels, downregulated neuroinflammation, and improved neurological recovery of TBI <em>in vivo</em>. This designed self-adaptive biomaterial effectively regulated the pathological microenvironment in injured tissue, and achieved better therapeutic effect.</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":"142141998","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":"Unveiling the mechanical role of radial fibers in meniscal tissue: Toward structural biomimetics","authors":"","doi":"10.1016/j.actbio.2024.08.024","DOIUrl":"10.1016/j.actbio.2024.08.024","url":null,"abstract":"<div><div>The meniscus tissue is crucial for knee joint biomechanics and is frequently susceptible to injuries resulting in early-onset osteoarthritis. Consequently, the need for meniscal substitutes spurs ongoing development. The meniscus is a composite tissue reinforced with circumferential and radial collagenous fibers; the mechanical role of the latter has yet to be fully unveiled.</div><div>Here, we investigated the role of radial fibers using a synergistic methodology combining meniscal tissue structure imaging, a computational knee joint model, and the fabrication of simple biomimetic composite laminates. These laminates mimic the basic structural units of the meniscus, utilizing longitudinal and transverse fibers equivalent to the circumferential and radial fibers in meniscal tissue.</div><div>In the computational model, the absence of radial fibers resulted in stress concentration within the meniscus matrix and up to 800 % greater area at the same stress level. Furthermore, the contact pressure on the tibial cartilage increased drastically, affecting up to 322 % larger areas. Conversely, in models with radial fibers, we observed up to 25 % lower peak contact pressures and width changes of less than 0.1 %. Correspondingly, biomimetic composite laminates containing transverse fibers exhibited minor transverse deformations and smaller Poisson's ratios. They demonstrated structural shielding ability, maintaining their mechanical performance with the reduced amount of fibers in the loading direction, similar to the ability of the torn meniscus to carry and transfer loads to some extent. These results indicate that radial fibers are essential to distribute contact pressure and tensile stresses and prevent excessive deformations, suggesting the importance of incorporating them in novel designs of meniscal substitutes.</div></div><div><h3>Statement of significance</h3><div>The organization of the collagen fibers in the meniscus tissue is crucial to its biomechanical function. Radially oriented fibers are an important structural element of the meniscus and greatly affect its mechanical behavior. However, despite their importance to the meniscus mechanical function, radially oriented fibers receive minor attention in meniscal substitute designs. Here, we used a synergistic methodology that combines imaging of the meniscal tissue structure, a structural computational model of the knee joint, and the fabrication of simplistic biomimetic composite laminates that mimic the basic structural units of the meniscus. Our findings highlight the importance of the radially oriented fibers, their mechanical role in the meniscus tissue, and their importance as a crucial element in engineering novel meniscal substitutes.</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":"142057492","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":"Stimuli-responsive drug delivery systems for inflammatory skin conditions","authors":"","doi":"10.1016/j.actbio.2024.08.037","DOIUrl":"10.1016/j.actbio.2024.08.037","url":null,"abstract":"<div><div>Inflammatory skin conditions highly influence the quality of life of the patients suffering from these disorders. Symptoms include red, itchy and painful skin lesions, which are visible to the rest of the world, causing stigmatization and a significantly lower mental health of the patients. Treatment options are often unsatisfactory, as they suffer from either low patient adherence or the risk of severe side effects. Considering this, there is a need for new treatments, and notably of new ways of delivering the drugs. Stimuli-responsive drug delivery systems are able to deliver their drug cargo in response to a given stimulus and are, thus, promising for the treatment of inflammatory skin conditions. For example, the use of external stimuli such as ultraviolet light, near infrared radiation, or alteration of magnetic field enables drug release to be precisely controlled in space and time. On the other hand, internal stimuli induced by the pathological condition, including pH alteration in the skin or upregulation of reactive oxygen species or enzymes, can be utilized to create drug delivery systems that specifically target the diseased skin to achieve a better efficacy and safety. In the latter context, however, it is of key importance to match the trigger mechanism of the drug delivery system to the actual pathological features of the specific skin condition. Hence, the focus of this article is placed not only on reviewing stimuli-responsive drug delivery systems developed to treat specific inflammatory skin conditions, but also on critically evaluating their efficacy in the context of specific skin diseases.</div></div><div><h3>Statement of significance</h3><div>Skin diseases affect one-third of the world's population, significantly lowering the quality of life of the patients, who deal with symptoms such as painful and itchy skin lesions, as well as stigmatization due to the visibility of their symptoms. Current treatments for inflammatory skin conditions are often hampered by low patient adherence or serious drug side effects. Therefore, more emphasis should be placed on developing innovative formulations that provide better efficacy and safety for patients. Stimuli-responsive drug delivery systems hold considerable promise in this regard, as they can deliver their cargo precisely where and when it is needed, reducing adverse effects and potentially offering better treatment outcomes.</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":"142115795","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":"Collagen-targeted protein nanomicelles for the imaging of non-alcoholic steatohepatitis","authors":"","doi":"10.1016/j.actbio.2024.08.052","DOIUrl":"10.1016/j.actbio.2024.08.052","url":null,"abstract":"<div><div><em>In vivo</em> molecular imaging tools hold immense potential to drive transformative breakthroughs by enabling researchers to visualize cellular and molecular interactions in real-time and/or at high resolution. These advancements will facilitate a deeper understanding of fundamental biological processes and their dysregulation in disease states. Here, we develop and characterize a self-assembling protein nanomicelle called collagen type I binding – thermoresponsive assembled protein (Col1-TRAP) that binds tightly to type I collagen <em>in vitro</em> with nanomolar affinity. For <em>ex vivo</em> visualization, Col1-TRAP is labeled with a near-infrared fluorescent dye (NIR-Col1-TRAP). Both Col1-TRAP and NIR-Col1-TRAP display approximately a 3.8-fold greater binding to type I collagen compared to TRAP when measured by surface plasmon resonance (SPR). We present a proof-of-concept study using NIR-Col1-TRAP to detect fibrotic type I collagen deposition <em>ex vivo</em> in the livers of mice with non-alcoholic steatohepatitis (NASH). We show that NIR-Col1-TRAP demonstrates significantly decreased plasma recirculation time as well as increased liver accumulation in the NASH mice compared to mice without disease over 4 hours. As a result, NIR-Col1-TRAP shows potential as an imaging probe for NASH with <em>in vivo</em> targeting performance after injection in mice.</div></div><div><h3>Statement of significance</h3><div>Direct molecular imaging of fibrosis in NASH patients enables the diagnosis and monitoring of disease progression with greater specificity and resolution than do elastography-based methods or blood tests. In addition, protein-based imaging probes are more advantageous than alternatives due to their biodegradability and scalable biosynthesis. With the aid of computational modeling, we have designed a self-assembled protein micelle that binds to fibrillar and monomeric collagen <em>in vitro.</em> After the protein was labeled with near-infrared fluorescent dye, we injected the compound into mice fed on a NASH diet. NIR-Col1-TRAP clears from the serum faster in these mice compared to control mice, and accumulates significantly more in fibrotic livers.This work advances the development of targeted protein probes for <em>in vivo</em> fibrosis imaging.</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":"142141997","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":"Cell-free decellularized skin matrix scaffolds: A promising approach for meniscus regeneration in a rabbit meniscectomy model","authors":"","doi":"10.1016/j.actbio.2024.08.014","DOIUrl":"10.1016/j.actbio.2024.08.014","url":null,"abstract":"<div><div>Tissue engineering presents a promising approach for the treatment of meniscal injuries, yet the development of meniscal scaffolds that exhibit both superior biomechanical properties and biocompatibility remains a considerable challenge. In this study, decellularized skin matrix (DSM) scaffolds were first prepared using porcine skin through decellularization and freeze-drying techniques. The DSM scaffold has favorable porosity, hydrophilicity, and biocompatibility. Importantly, the collagen content and tensile modulus of the scaffold are comparable to those of native meniscus (44.13 ± 2.396 mg/g <em>vs</em>. 42.41 ± 2.40 mg/g and 103.30 ± 2.98 MPa <em>vs</em>. 128.80 ± 9.115 MPa). Subsequently, the peptide PFSSTKT (PFS) with mesenchymal stem cells (MSCs) recruitment capability was used to modify DSM to construct DSM-PFS scaffolds. Compared to the DSM scaffold, the optimized DSM-PFS scaffold enhanced <em>in vitro</em> collagen and glycosaminoglycan (GAG) production and upregulated the expression of cartilage-specific genes. Furthermore, the DSM-PFS scaffold was more effective in recruiting MSCs <em>in vitro. In vivo</em> studies in rabbit models showed that the DSM-PFS scaffold successfully promoted meniscus tissue regeneration. Three months post-implantation, meniscus tissue formation can be observable, and after six months, the neo-meniscus exhibited tissue structure and tensile properties similar to the native meniscus. Notably, the DSM-PFS scaffold exhibited significant chondroprotective effects, slowing osteoarthritis (OA) progression. In conclusion, the DSM-PFS scaffold may represent a promising candidate for future applications in meniscus tissue engineering.</div></div><div><h3>Statement of significance</h3><div>We developed a decellularized skin matrix (DSM) meniscus scaffold using whole-layer porcine skin, demonstrating superior biomechanical strength and biocompatibility. Following modification with the stem cell-recruiting peptide PFS, the optimized DSM-PFS scaffold outperformed the DSM scaffold in cell attraction, collagen and glycosaminoglycan production, and cartilage-specific gene expression. Implanted into rabbit knee joints, the cell-free DSM-PFS scaffold induced meniscal tissue formation within three months, achieving the histological structure and tensile strength of the native meniscus by six months. Moreover, it significantly protected the cartilage. Our findings provide new insights into the fabrication of scaffolds for meniscal tissue engineering, with the DSM-PFS scaffold emerging as an ideal candidate for future applications.</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":"142019825","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":"Angiogenesis and full thickness wound repair in a cell sheet-based vascularized skin substitute","authors":"","doi":"10.1016/j.actbio.2024.08.023","DOIUrl":"10.1016/j.actbio.2024.08.023","url":null,"abstract":"<div><div>Skin tissue engineering is undergoing tremendous expansion as a result from clinical needs, mandatory replacement of animal models and development of new technologies. Many approaches have been used to produce vascularized skin substitutes for grafting purposes showing the presence of capillary-like structures but with limited analysis of their <em>in vitro</em> maturation and plasticity. Such knowledge is however important for the development of tissue substitutes with improved implantation success as well as for validation of vascularization <em>in vitro</em> models, including as a readout in pharmacological analyses. For optimal interactions of cells with microenvironment and vasculature, we here used a cell sheet approach consisting in the sole production of matrix by the cells. In this context, we limited the density of endothelial cells seeded for self-assembly and rather relied on the stimulation of angiogenesis for the development of an extensive connected microvascular-like network. After detailed characterization of this network, we challenged its plasticity both during and after establishment of the skin substitute. We show that fine tuning of VEGF concentration and time of application differentially affects formation of capillary-like structures and their perivascular coverage. Furthermore, we performed a deep wound assay that displayed tissue repair and angiogenesis with unique characteristics of the physiological process. These studies demonstrate the importance of cell-derived microenvironment for the establishment of mature yet dynamic vascularized skin models allowing a wide range of pharmacological and basic investigations.</div></div><div><h3>Statement of significance</h3><div>The significant advancements in organ-on-chips and tissue engineering call for more relevant models including microvascularization with remodeling potential. While vascularized skin substitutes have been developed for years, focus has primarily been on the impact of microvascularization on implantation rather than on its <em>in vitro</em> characterization. We here developed a cell sheet-based vascularized skin substitute relying on angiogenesis, <em>i.e.</em> growth of vessel-like structures within the 3D model, rather than solely on endothelial cell self-assembly. We then characterized :1/ vascularization after modulation of angiogenic factor VEGF during the substitute construction; -2/ angiogenesis associated to tissue repair after deep mechanical wounding. These studies establish a solid physiologically relevant model for further investigation of skin cell interactions and <em>in vitro</em> wound healing.</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":"142057486","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}