Acta biomaterialia最新文献

{"title":"Mesoscale Mineral Clusters in Osteonal Bone Follow the Twisted Plywood Structure of Collagen.","authors":"Alyssa Williams, Thomas Cotty, Tengteng Tang, Michael W Phaneuf, Nabil Bassim, Aurélien Gourrier, Kathryn Grandfield","doi":"10.1016/j.actbio.2025.10.003","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.10.003","url":null,"abstract":"<p><p>The structure of bone at the nano to microscale contributes to its functions, including its mechanical strength. A new hierarchical feature was recently discovered at the mesoscale: ellipsoidal-shaped mineral clusters. While a great deal of imaging has been completed on bone, the packing and spatial organization between the mesoscale mineral clusters and nanoscale features, such as collagen fibrils, is largely absent. This is partly due to the technical 3D nanoscale imaging challenges, which have impacted the ability to resolve collagen fibril banding in fully mineralized bone in multiple planes, and partly due to a lack of image processing tools to visualize characteristic details of the collagen fibril and mineral cluster arrangement from 3D volumes. Herein, FIB-SEM nanotomography of mineralized osteonal bone revealed mineral clusters with an average diameter of 600-700 nm yielding an estimate of 8 clusters per lamellae. Mineral clusters were found to follow the well-known twisted plywood organization of collagen fibrils and low-mineralized collagen fibrils defining the border of the clusters were found to be within ±30^o of the long axis of the mineral cluster. Clusters were also found to be spatially correlated with distinct symmetry motifs, indicating some degree of local ordering. Further, we show that what was previously thought to be pores or nanochannels surrounding mineral clusters may be, in large part, collagen fibrils. This work unveils new insights into the links between the meso- and nanoscale organization of bone, reinforcing its hierarchical nature. STATEMENT OF SIGNIFICANCE: Advances in 3D-focused ion beam scanning electron nanotomography have enabled high-resolution visualization of the relationship between the mineral and organic content within the osteonal bone. While the nanoscale collagen fibril organization has been heavily investigated using 2D and 3D imaging techniques, the arrangement of mesoscale mineral ellipsoids has not been characterized in depth. Using FIB-SEM nanotomography and advanced image processing tools, including deep learning segmentation, FFT processing with azimuthal profile integration, and autocorrelation analysis, our results display the close association of the mineral ellipsoids and the collagen fibril network within human osteonal bone where the mineral ellipsoids appear to have local ordering that follows a twisted plywood organization similar to the collagenous matrix.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal distribution of engineered biodegradable urease-powered nanomotors.","authors":"Helena Almeida, Cecília Cristelo, Juliana Viegas, Giovanni Traverso, Bruno Sarmento, José das Neves","doi":"10.1016/j.actbio.2025.10.004","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.10.004","url":null,"abstract":"<p><p>The oral route is the most patient-friendly option for drug administration, yet biological barriers often limit its effectiveness. Chief among these is the mucus layer along the gastrointestinal (GI) tract, which restricts the transport of drugs and carriers. Strategies such as mucolytics, mucus-inert materials, and anisotropic nanosystems have been employed to enhance penetration. We developed urease-powered poly(lactic-co-glycolic acid) (PLGA) nanomotors for drug delivery, featuring either random (isotropic) or spatially localized (anisotropic, Janus-like) urease surface functionalization. Anisotropic nanomotors were prepared by immobilizing PLGA nanoparticles (NPs) at the oil-water interface of Pickering emulsions, followed by urease conjugation via carbodiimide chemistry. Cryogenic scanning electron microscopy confirmed interfacial localization and immunoelectron microscopy unveiled urease spatial distribution. The resulting nanomotors catalyzed the conversion of urea to ammonia and carbon dioxide, enabling enhanced diffusion in urea-containing environments. Isotropic NPs showed a two-fold higher enzymatic conversion rate compared to anisotropic ones, attributed to higher enzyme availability, with negligible levels observed for passive PLGA NPs. All NPs were coated with poloxamer 407 (P407) for stabilization, yielding particles under 200 nm with low polydispersity and near-neutral charge. The P407 coating slightly reduced nanomotor mobility in fluids at the single-particle level, while it seems to have improved in vitro cell uptake in the presence of urea. In vivo studies in rats revealed that urease-functionalized nanomotors transited the GI tract and appeared to show enhanced localization at the epithelial surface, when compared to passive counterparts and regardless of urease distribution configuration. These findings highlight the potential of both isotropic and anisotropic urease-powered PLGA nanomotors to overcome GI barriers and serve as drug delivery platforms. STATEMENT OF SIGNIFICANCE: New designs for urease-powered polymeric nanoparticles (nanomotors) are proposed in this work to circumvent hurdles introduced by mucosae. Nanomotors featured either random or spatially oriented distribution of urease at their surface. The latter was achieved by means of Pickering emulsion and partial surface modification. Using these approaches, we demonstrated that both nanomotors convert urea into carbon dioxide and ammonia, resulting in enhanced diffusion in aqueous media. Nanomotors were safe in vitro, and capable of providing extensive distribution throughout the gastrointestinal tract following oral administration to rats, accumulating in the vicinity of the epithelium. The main findings suggest that such bioresorbable nanosystems have the potential to tackle important biological barriers and presumably be used as oral drug delivery vehicles.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymmetric Mechanical Behavior and pre-osteoblast differentiation in Ti-6Al-4V Minimal-Surface Bone-Analogues: The Role of Pore Topology.","authors":"Bijay Kumar Karali, Suresh Suthar, Sushant Banerji, Bikramjit Basu","doi":"10.1016/j.actbio.2025.10.002","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.10.002","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The manufacturability of the cellular structure-based materials represents one of the most emerging themes in the additive manufacturing of medical implants and devices. This has been more relevant as natural bone possesses a unique porous architecture, which cannot be mimicked in conventional manufacturing. Despite recent advances, a critical knowledge gap persists in connecting scaffold topology and manufacturability with the mechano-biological responses, governed by asymmetric 3D pore structures. In this perspective, the present study focuses on selective laser melting of Schwarz diamond-based triply periodic minimal surface (TPMS) structures in Ti6Al4V, while varying unit cell size from 2.5 to 3.0 mm. The extensive micro-computed tomography analysis of 3D pore topology using customised design evaluation protocols established the efficacy of SLM-based optimised process parameters on dimensional tolerance and manufacturability of the TPMS structures. Intriguingly, an asymmetric mechanical response with a clinically relevant combination of the compressive elastic modulus (14-20 GPa), tensile elastic modulus (38 - 55 GPa), compressive strength (413-547 MPa), and tensile strength (325-475MPa), together with unique 3D pore architecture, closely resembled the properties of human cortical bone. While fitting the strength/modulus to relative density data using the Gibson-Ashby model, the bending-dominated asymmetric microstructural response was revealed with exponents of ∼1.5 in compression and ∼2.0 in tension. Furthermore, in vitro studies demonstrate MC3T3-E1 pre-osteoblasts' adhesion, proliferation, and maturation with modulation of early osteogenic markers and bone mineralisation, both quantitatively and qualitatively. The confocal microscopy observations revealed the cellular bridging, migration, and colonisation, indicating cytocompatibility. The present study conclusively establishes that SDW-TPMS structures offer a compelling combination of cortical bone-mimicking mechanical properties and a favourable biological response. It highlights their potential for reconstructive surgeries of load-bearing joints. STATEMENT OF SIGNIFICANCE: Conventional high-modulus metallic implants can induce periprosthetic bone resorption via stress shielding. While additively manufactured porous biomaterials address this, a robust structure-property-function paradigm has remained elusive. This study presents a Ti-6Al-4V minimal-surface scaffold that achieves the biomechanical fidelity for load-bearing applications while providing a microenvironment suitable for differentiataion of pre-osteoblasts. The central innovation is our use of quantitative pore network modeling to establish a predictive link between the as-manufactured pore topology, the scaffold's pronounced tension-compression asymmetry, and its pro-osteogenic biological response. This work provides a validated framework for the rational design of next-generation bio-integrated orthopedic implants.&lt;/p","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional cell spheroid technology: Recent advances and emerging strategies in cartilage regeneration.","authors":"Huancong Liu, Chengkun Zhao, Jie Liang, Yujiang Fan, Yong Sun, Xingdong Zhang","doi":"10.1016/j.actbio.2025.10.001","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.10.001","url":null,"abstract":"<p><p>Three-dimensional (3D) cell spheroid technology has led to significant advances in cartilage injury repair, the construction of osteoarthritis (OA) models, and the development of platforms for screening therapeutics targeting cartilage diseases. Compared with conventional two-dimensional (2D) cell culture, this technology better mimics the in vivo microenvironment, thus providing stronger support for cell growth and viability. Furthermore, it effectively stimulates chondrocytes proliferation and differentiation, facilitating cartilage tissue regeneration and significantly improving the quality and efficiency of cartilage regeneration. However, the clinical translation of this technology is hindered by several major challenges, including the limited long-term stability of cell spheroids, difficulties in large-scale production, and immune rejection following implantation in vivo. Advancements in materials science, machine learning (ML), and single-cell RNA sequencing (scRNA-seq) are expected to enable personalized and standardized 3D cell spheroid biofabrication. These advancements are likely to provide precise and efficient therapeutic solutions for cartilage regenerative medicine, thereby advancing cartilage regeneration and regeneration to unprecedented levels in translational applications. STATEMENT OF SIGNIFICANCE: Three-dimensional (3D) cell spheroid technology represents a significant advancement in cartilage regeneration due to its ability to mimic the native cartilage microenvironment, enhance cell-cell interactions, promote extracellular matrix production, and improve tissue repair outcomes. This review highlights recent developments in spheroid formation mechanisms, engineering strategies, and clinical applications. It also discusses key challenges such as large-scale production and immune safety, while exploring emerging solutions involving smart biomaterials and machine learning. This comprehensive summary provides broad insights into the translational potential of 3D cell spheroids for regenerative medicine. We believe this review may serve as a practical guide for biomaterials researchers.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxyapatite-Based Coatings for Corrosion Resistance and Self-healing in Biomedical and Industrial Applications.","authors":"Chandrabhan Verma, Seul-Yi Lee, Jagadis Gautam, Shikha Dubey, Prashant Singh, Kyong Yop Rhee, Eno E Ebenso, Akram Alfantazi, Soo-Jin Park","doi":"10.1016/j.actbio.2025.09.054","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.054","url":null,"abstract":"<p><p>Understanding and controlling the relationship between biomaterial structure and biological function is essential for the long-term success of biomedical implants. Hydroxyapatite (HAp), a biocompatible calcium phosphate-like bone mineral, has garnered attention as a multifunctional coating material due to its corrosion resistance and bioactivity. This review critically examines recent advances in HAp-based coatings, with a focus on fabrication techniques, microstructural design, and corrosion protection mechanisms. Emphasis is placed on functional enhancements through surface engineering, ion substitution (e.g., F⁻, Zn²⁺, Sr²⁺), coordination chemistry, and incorporation with nanocomposites, such as carbon allotropes, biopolymers, and metal oxides. The dual role of HAp in promoting osteointegration and preventing localized corrosion is explored across diverse metallic substrates (Mg, Ti, NiTi, and stainless steel), with comparative insights from saline and simulated body fluids (SBFs) environments. The review also highlights emerging smart coatings with diagnostic and self-healing capabilities, offering guidance for the development of next-generation HAp-based coatings for durable and multifunctional biomedical implants. STATEMENT OF SIGNIFICANCE: Hydroxyapatite (HAp), a calcium phosphate mineral, has been established as a useful material due to its remarkable bioactivity and biocompatibility. Numerous existing studies explore the use of HAp in bone regeneration and integration; however, its potential in multifunctional coatings leftovers underexplored. The present review explores the growing interest and significance of the HAp-based coatings in ensuring the corrosion resistance of metallic implants. HAp provides an environmentally friendly and non-toxic alternative to the traditional coatings or inhibiting systems that suffer from limited durability, poor adhesion, and toxicity. HAp-based coatings are associated with self-healing, biocompatibility, and osteointegration capabilities along with anticorrosion potentials. This review explores advancements in synthesis, ion substitution, nanocomposites, and smart self-healing systems, providing insights for next-generation implant coatings, enhancing longevity, patient safety, and corrosion protection.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomechanical characterization of the human pia-arachnoid complex using bulge inflation testing and the virtual fields method.","authors":"Paulien Vandemaele, Heleen Fehervary, Lauranne Maes, Bart Depreitere, Jos Vander Sloten, Nele Famaey","doi":"10.1016/j.actbio.2025.09.035","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.035","url":null,"abstract":"<p><p>The cranial meninges are crucial structures in protecting the brain against injury. Hence, a biofidelic mechanical representation of these tissues is essential for accurate computational predictions of stress and strain in the brain during a traumatic brain injury. This study presents a biomechanical analysis of human pia-arachnoid complex tissue, which is formed by the two innermost meningeal layers. Bulge inflation experiments were performed on 29 pia-arachnoid complex samples to investigate their in-plane mechanical properties and parameters of the modified one-term Ogden model were derived with the virtual fields method. Due to its anatomical structure, pia-arachnoid complex tissue has an inhomogeneous thickness with a median value of 0.400mm. A bivariate normal probability density function was identified for the log-transformed parameters obtained from different specimens and samples with mean values μ=0.30MPa and α=36.97. Results show that the mechanical behavior of pia-arachnoid complex tissue is highly nonlinear in contrast to the linear elastic models often implemented in state-of-the-art finite element head models. Since the pia-arachnoid complex tissue is closely wrapped around the brain, it is important to include a more realistic mechanical behavior into these models. Statement of significance This study presents a biomechanical characterization of the human pia-arachnoid complex tissue by employing advanced techniques such as bulge inflation testing and the virtual fields method. To the best of the author's knowledge, this research is the first to characterize the in-plane properties of the human pia-arachnoid complex tissue. Additionally, this is also the first time that properties of the pia-arachnoid complex tissue are derived based on multiaxial testing. These findings are crucial for understanding the protective function of the pia-arachnoid complex in the brain. Furthermore, this research is also a critical step towards developing more accurate computational models of the human head, which are essential for studying traumatic brain injuries.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosylation-enabled Chemoselective Growth Factor Engineering for Biomaterial Functionalization.","authors":"Yunhui Xing, Qingyang Li, Ellen L Otto, Phil G Campbell, Xi Ren","doi":"10.1016/j.actbio.2025.09.057","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.057","url":null,"abstract":"<p><p>In native tissue environments, growth factors (GFs) are often physically associated with the extracellular matrix (ECM) framework. Despite the enormous potential of chemoselective click chemistry for biomaterial functionalization to recapitulate such GF-ECM association, its application remains limited by constraints in the reliable production of clickable GFs. Here we present a platform technology that leverages intrinsic post-translational protein glycosylation to enable chemoselective engineering of GFs to incorporate click-reactive azido tags for subsequent ECM conjugation. Using Vascular Endothelial Growth Factor as a model, we demonstrated efficient, glycosylation-dependent azido incorporation during its recombinant expression with preserved bioactivity. We further expanded the utility of this strategy to non-glycosylated proteins through engineered N-linked glycosylation via the incorporation of a signal peptide, to direct newly synthesized proteins to the secretory pathway where glycosylation takes place, along with sequons for glycan attachment. The resulting GF with chemoselective azido incorporation can be effectively immobilized within dibenzocyclooctyne-bearing ECM hydrogel via the copper-free click chemistry, exhibiting sustained GF retention and delivering augmented angiogenic responses. Our approach thereby offers an opportunity to streamline recombinant protein engineering for biomaterial functionalization in tissue engineering and regenerative medicine applications. STATEMENT OF SIGNIFICANCE: This manuscript describes a novel approach that uses natural sugar modification (glycosylation) of proteins to precisely modify growth factors (GFs) in a site-specific manner. By adding special chemical tags (azido tags) to these proteins, our approach streamlines the use of click chemistry for boosting biomaterial performance. Typically, each GF requires extensive individual optimization; however, our universal method simplifies the process, improving GF retention and functionality within biomaterials. Additionally, the technique can be applied to proteins that don't naturally have these sugar modifications by introducing engineered glycosylation. Overall, this technology offers an easy-to-use platform for researchers in tissue engineering, enhancing their ability to precisely place and deliver therapeutic proteins within biomaterial scaffolds, ultimately benefiting the broader field of regenerative medicine.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microenvironment-Modulating Hyaluronic Acid-Tannic Acid Hydrogel for Peripheral Nerve Injury Repair.","authors":"Yao Liu, Kai Liu, Yu Yan, Xiaonong Zhang, Chunsheng Xiao, Zhiming Song, Bin Liu","doi":"10.1016/j.actbio.2025.09.056","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.056","url":null,"abstract":"<p><p>Peripheral nerve injury typically results in the loss of nervous tissues and motor and sensory functions, leading to serious clinical complications. Excessive oxidative stress and inflammations in the damaged area can severely inhibit nerve regeneration, making the repair of damaged nerve tissues challenging. In this study, we developed a microenvironment-modulating hyaluronic acid-based hydrogel crosslinked with tannic acid (HPTA) and evaluated its effectiveness in treating peripheral nerve injury. The prepared hydrogel demonstrates good injectability, antioxidative and anti-inflammatory properties, and good biocompatibility. By modulating the microenvironmental oxidative stress and reducing inflammation in damaged areas, the HPTA hydrogel effectively improved the motor function in rats with sciatic nerve crush injury, significantly reduced muscular atrophy, protected neuronal, and enhanced nerve regeneration and remyelination. Additionally, the HPTA@MeCbl hydrogel, loaded with a therapeutic agent methylcobalamin (MeCbl), showed enhanced treatment of damaged nerves through gradually releasing MeCbl at the injury site. Animal studies demonstrated that HPTA@MeCbl hydrogel significantly promotes functional recovery and axonal regeneration in the lower limbs after sciatic nerve transection. In conclusion, the microenvironment-modulating HPTA hydrogel developed in this study offers a promising strategy for developing high-performance biomaterials for nerve repair. STATEMENT OF SIGNIFICANCE: Peripheral nerve injury remains a major clinical challenge due to limited regenerative capacity and the hostile microenvironment characterized by oxidative stress and inflammation. This study presents a hyaluronic acid-based hydrogel crosslinked with tannic acid (HPTA) that actively modulates the injury microenvironment by attenuating oxidative stress and inflammation, thereby facilitating nerve regeneration. Furthermore, incorporating methylcobalamin (MeCbl) into the hydrogel (HPTA@MeCbl) enables localized and sustained drug release, significantly enhancing axonal regrowth and functional recovery in both crush and transection nerve injury models. This work introduces a clinically translatable, microenvironment-modulating hydrogel platform with dual therapeutic functionalities, offering a promising strategy for advanced peripheral nerve repair.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multiscale finite element model of fluid-microstructure interactions in human intervertebral disc compression.","authors":"Ugo Cachot, Karim Kandil, Fahmi Zaïri, Fahed Zaïri","doi":"10.1016/j.actbio.2025.09.048","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.048","url":null,"abstract":"<p><p>The human intervertebral disc (IVD) is a complex, anisotropic structure composed of the nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplates (CEPs), which together enable the spine to bear loads and accommodate multi-directional motion. Although experimental studies have revealed the nonlinear, time-dependent, and region-specific mechanical behavior of the IVD, capturing this complexity in computational models remains a major challenge. This study extends a previously validated biphasic finite element model of the AF - incorporating collagen fiber networks and interlamellar structures - into a full-scale IVD model that accounts for the heterogeneous, anisotropic, and fluid-solid coupled properties of all components. A multiscale identification strategy links experimental microstructural properties to macroscopic behavior, and an automated meshing approach enables systematic variations in geometric features. The model is validated against a broad set of experimental data under three compressive loading protocols: compressive creep-recovery, cyclic compression, and stepwise compression-relaxation. Numerical results reproduce global and regional IVD mechanics, including energy absorption, strain-rate sensitivity, and spatial strain heterogeneity, governed by fluid-microstructure interactions. The study also evaluates key experimental factors - such as preload duration, hydration, and geometry - highlighting their influence on the IVD response. These findings demonstrate the predictive strength of the multiscale biphasic approach, providing a robust computational foundation for advancing IVD biomechanics and supporting future clinical applications in spine health and degeneration. STATEMENT OF SIGNIFICANCE: This study introduces a validated multiscale finite element model that simulates the time-dependent behavior of the human intervertebral disc by capturing key fluid-microstructure interactions. Building on previous modeling of the annulus fibrosus, this framework extends to the full disc, integrating the biphasic, fiber-reinforced lamellar structure of the annulus and its coupling with the nucleus pulposus. Parameters are identified from experimental data and validated under multiple loading scenarios, including creep-recovery, cyclic compression, and stepwise compression-relaxation. The model reproduces global mechanical behavior and regional strain distributions, emphasizing the roles of fiber recruitment, fluid redistribution, and anatomical variation. This work enhances our understanding of disc biomechanics and offers a predictive platform for investigating disc degeneration and guiding repair strategies.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SELF-ASSEMBLED PEPTIDE RADA16 HYDROGEL PROMOTES EPITHELIALIZATION OF WOUNDS BY A LAMININ-332-DEPENDENT SCAVENGING MECHANISM.","authors":"Chloé Laigle, Marie Buffier, Emélie Clémens, Sharanya Sankar, Patricia Rousselle","doi":"10.1016/j.actbio.2025.09.055","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.055","url":null,"abstract":"<p><p>Re-epithelialization describes the resurfacing of a skin wound with new epidermis as the first step in restoring its integrity and barrier function. In wounds, re-epithelialization progresses from the surrounding wound edges towards the center, forming a continuum in the regeneration of a differentiated epidermis by adhesion to extracellular matrix proteins. Failure of re-epithelialization is a hallmark of chronic wounds and keeps them in a vicious cycle of infection and uncontrolled inflammation that impairs healing. With the increasing number of all forms of chronic wounds, there is an urgent need to develop appropriate therapeutics. To address the lack of a therapeutic solution specifically targeting this burden, we focused on the self-assembling peptide hydrogel RADA16, whose biocompatibility and therapeutic validation for use in humans as a hemostatic agent make it an attractive candidate. Due to its ability to adopt different stiffness and stability properties depending on the peptide concentration, we investigated its most promising formulation to support epidermal regeneration. Our study shows that RADA16 is able to promote keratinocyte adhesion, proliferation and migration, enabling wound closure both in vitro and in vivo. We demonstrate the original mechanism of action based on RADA16-specific recruitment of the keratinocyte major adhesion protein laminin-332, which is essential for these cellular processes. We also show that RADA biomimetically mimics the tripeptide cell adhesion sequence RGD for both laminin recruitment and dermal fibroblast adhesion. Our study describes the repositioning of the RADA16 hydrogel as the first synthetic, hydrating, stable and resorbable hydrogel that promotes rapid re-epithelialization of wounds through an endogenous and spontaneous laminin-332 functionalization mechanism. STATEMENT OF SIGNIFICANCE: The study reports on the complete characterization of a self-assembling peptide hydrogel (RADA16), already in clinical use for its hemostatic properties, with a view to its repositioning for the reepithelialization of skin wounds. The focus on this indication is important as there is currently no hydrogel with healing-promoting properties in clinical practice. The work is significant as it provides an in-depth investigation of the mechanism by which RADA16 promotes wound resurfacing, based on its endogenous and spontaneous functionalization by the extracellular matrix protein laminin-332, the major adhesion protein produced by epidermal cells. The combination of basic research for therapeutic development with consideration of a global public health problem are assets that characterize this study.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}