Acta Biomaterialia最新文献

{"title":"Natural coil springs: Biomechanics and morphology of the coiled tendrils of the climbing passion flower Passiflora discophora","authors":"Frederike Klimm ,&nbsp;Marc Thielen ,&nbsp;Jaro Homburger ,&nbsp;Michelle Modert ,&nbsp;Thomas Speck","doi":"10.1016/j.actbio.2024.10.002","DOIUrl":"10.1016/j.actbio.2024.10.002","url":null,"abstract":"<div><div>Tendrils of climbing plants possess a striking spring-like structure characterized by a minimum of two helices of opposite handedness connected by a perversion. By performing tensile experiments and morphological measurements on tendrils of the climbing passion flower <em>Passiflora discophora</em>, we show that these tendril springs act as coil springs within the plant's attachment system and resemble technical coil springs. However, tendril springs have a low spring index and a high pitch angle compared with typical metal coil springs resulting in a more complex loading situation in the plant tendrils. Moreover, the tendrils undergo a drastic shift from the fresh turgescent stage to a dried-off and dead senescent stage. This entails changes in material properties (elastic modulus in tension), morphology (tendril and helix diameter, number of windings), anatomy (tissue composition), and failure behavior (susceptibility to delamination) and reduces the degree of elasticity and strain at failure of the tendrils. Nevertheless, senescent tendrils remain functional as springs and maintain high energy dissipation capacity and high break force. This renders the system highly energy efficient, as the plant no longer needs to metabolically sustain the died-back tendrils. Because of its energy-storing spring system, its high energy dissipation and high safety factor, the attachment system can be considered a ‘fail-safe’ system.</div></div><div><h3>Statement of significance</h3><div>The use of coil springs as mechanical devices is not restricted to man-made machinery; striking spring structures can also be found within the attachment systems of climbing plants. <em>Passiflora discophora</em> climbs by using long thin tendrils with adhesive pads at their tips. Once the pads have attached to a support, the tendrils coil and form a spring-like structure. Here, we analyze the form and mechanics of these ‘tendril springs’, compare them with conventional technical coil springs, and discuss changes in the tendril springs during plant development. We reveal the main features of the attachment system, which might inspire new artificial attachment devices within the emerging field of plant-inspired soft-robotics.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 478-490"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407321","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":"Protein-metal interactions due to fretting corrosion at the taper junction of hip implants: An in vitro investigation using Raman spectroscopy","authors":"Adrian Wittrock ,&nbsp;Saskia Heermant ,&nbsp;Christian Beckmann ,&nbsp;Markus A. Wimmer ,&nbsp;Alfons Fischer ,&nbsp;Marc Aßmann ,&nbsp;Jörg Debus","doi":"10.1016/j.actbio.2024.10.006","DOIUrl":"10.1016/j.actbio.2024.10.006","url":null,"abstract":"<div><div>Modular hip implants are a clinically successful and widely used treatment for patients with arthritis. Despite ongoing retrieval studies the understanding of the fundamental physico-chemical mechanisms of friction and wear within the head-taper interface is still limited. Here, we Raman-spectroscopically analyze structural features of the biotribological material which is formed within the taper joint between Ti6Al4V and low-carbon cobalt alloy or high-nitrogen steel surfaces in <em>in vitro</em> gross-slip fretting corrosion tests with bovine calf serum. As a function of the fretting duration, we investigate short and long aliphatic chains and their adsorption behavior on the cobalt- and steel-type surfaces. Using the intensity and frequency shifts of the amide I and III Raman bands, we furthermore identify progressive protein folding and unfolding including the secondary structures of <span><math><mi>α</mi></math></span>-helix, <span><math><mi>β</mi></math></span>-sheet, and random-coil configuration as well as the formation of proteinaceous clusters depending on the hydrophilicity of the metallic surfaces. We additionally find a mixture of chromates and iron oxides with tryptophan and tyrosine at the worn cobalt alloy and high-nitrogen steel surfaces, respectively. Also, for long fretting duration, sp<span><math><msup><mrow></mrow><mn>2</mn></msup></math></span> hybridized amorphous carbon is formed due to fretting-induced cleavage of proteins.</div></div><div><h3>Statement of significance</h3><div>Despite efforts enhancing the biomedical tribology of hip implants, the impact of the organic environment on friction and wear at the femoral head-stem taper interface is limitedly understood. Using Raman spectroscopy we resolve structural changes within the biotribological material agglomerated at biomedical-grade metal alloys due to metal-organic interactions during <em>in vitro</em> fretting corrosion tests. Adsorption of short and long aliphatic chains, progressive protein (un)folding and proteinaceous cluster formation depend to a distinguishable extent on the fretting duration and type of alloy. Chromates and iron oxides are mixed with tryptophan and tyrosine, and amorphous carbon is formed resulting from a fretting-induced cleavage of serum proteins. Such information spectroscopically gleaned from biotribological material are vital to improve the design and performance of taper junctions.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 621-632"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407322","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":"Karen L. Christman, 2025 Acta Biomaterialia Silver Medal Award Recipient","authors":"","doi":"10.1016/j.actbio.2024.07.048","DOIUrl":"10.1016/j.actbio.2024.07.048","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Page 670"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657329","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":"Titanium boride nanosheets with photo-enhanced sonodynamic efficiency for glioblastoma treatment","authors":"Jiaqing Xu,&nbsp;Ying Liu,&nbsp;Han Wang,&nbsp;Junxing Hao,&nbsp;Yu Cao,&nbsp;Zhihong Liu","doi":"10.1016/j.actbio.2024.09.025","DOIUrl":"10.1016/j.actbio.2024.09.025","url":null,"abstract":"<div><div>Sonodynamic therapy (SDT) has garnered significant attention in cancer treatment, however, the low-yield reactive oxygen species (ROS) generation from sonosensitizers remains a major challenge. In this study, titanium boride nanosheets (TiB₂ NSs) with photo-enhanced sonodynamic efficiency was fabricated for SDT of glioblastoma (GBM). Compared with commonly-used TiO₂ nanoparticles, the obtained TiB₂ NSs exhibited much higher ROS generation efficiency under ultrasound (US) irradiation due to their narrower band gap (2.50 eV). Importantly, TiB₂ NSs displayed strong localized surface plasmon resonance (LSPR) effect in the second near-infrared (NIR II) window, which facilitated charge transfer rate and improved the separation efficiency of US-triggered electron–hole pairs, leading to photo-enhanced ROS generation efficiency. Furthermore, TiB₂ NSs were encapsulated with macrophage cell membranes (CM) and then modified with RGD peptide to construct biomimetic nanoagents (TiB₂@CM-RGD) for efficient blood-brain barrier (BBB) penetrating and GBM targeting. After intravenous injection into the tumor-bearing mouse, TiB₂@CM-RGD can efficiently cross BBB and accumulate in the tumor sites. The tumor growth was significantly inhibited under simultaneous NIR II laser and US irradiation without causing appreciable long-term toxicity. Our work highlighted a new type of multifunctional titanium-based sonosensitizer with photo-enhanced sonodynamic efficiency for GBM treatment.</div></div><div><h3>Statement of significance</h3><div>Titanium boride nanosheets (TiB₂ NSs) with photo-enhanced sonodynamic efficiency was fabricated for SDT of glioblastoma (GBM). The obtained TiB₂ NSs displayed strong localized surface plasmon resonance (LSPR) effect in the second near-infrared (NIR II) window, which facilitated charge transfer rate and improved the separation efficiency of US-triggered electron-hole pairs, leading to photo-enhanced ROS generation efficiency. Furthermore, TiB₂ NSs were encapsulated with macrophage cell membranes (CM) and then modified with RGD peptide to construct biomimetic nanoagents (TiB₂@CM-RGD) for efficient blood-brain barrier (BBB) penetrating and GBM targeting. After intravenous injection into the tumor-bearing mouse, TiB₂@CM-RGD can efficiently cross BBB and accumulate in the tumor sites. The tumor growth was significantly inhibited under simultaneous NIR II laser and US irradiation without causing appreciable long-term toxicity.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 344-357"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303142","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":"Reversible pH-switchable NIR-II nano-photosensitizer for precise imaging and photodynamic therapy of tumors","authors":"Yun Chai ,&nbsp;Ye Sun ,&nbsp;Zhijia Sheng ,&nbsp;Yanyan Zhu ,&nbsp;Tianyou Du ,&nbsp;Bingjian Zhu ,&nbsp;Hui Yu ,&nbsp;Bin Dong ,&nbsp;Yi Liu ,&nbsp;Hai-Yan Wang","doi":"10.1016/j.actbio.2024.09.001","DOIUrl":"10.1016/j.actbio.2024.09.001","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) has attracted widespread attention from researchers as an emerging cancer treatment method. There have been many reports on various types of NIR-II photosensitizers for imaging and treatment of tumor sites. However, there are few reports on the development of NIR-II organic small molecule photosensitizers that have intelligent response to the tumor microenvironment, precise imaging, real-time treatment, and high biocompatibility. In this work, we developed a series of NIR-II photosensitizers (RBTs) with near-infrared excitation, good photostability, and large Stokes shift. Among them, RBT-Br exhibited higher reactive oxygen species (ROS) generation efficiency due to the introduction of halogen heavy atoms to enhance intersystem crossing (ISC). It is noteworthy that RBT-Br can generate singlet oxygen (¹O₂) and superoxide anion radicals (^•O₂⁻) simultaneously under 730 nm laser. Subsequently, we used molecular engineering technology to construct three pH-responsive NIR-II photosensitizers (RBT-pHs) by utilizing the closure of the lactam ring, among which RBT-pH-1 (p<em>K</em>_a = 6.78) is able to be directionally activated under the stimulation of tumor micro-acid environment, with its fluorescence emission window reaching 933 nm. Subsequently, RBT-pH-1 NPs encapsulated in DSPE-mPEG_5k were applied for PDT treatment of mouse tumors. The results showed that RBT-pH-1 NPs were activated by the acidic tumor microenvironment and generated ROS under laser excitation, exhibiting precise tumor imaging and significant tumor growth inhibition. We look forward to these multifunctional NIR-II organic small molecule photosensitizers providing a more efficient approach for clinical treatment of tumors.</div></div><div><h3>Statement of significance</h3><div>A reversible pH-switchable NIR-II nano-photosensitizer RBT-pH-1 NPs (p<em>K</em>_a = 6.76) is developed for precise imaging and PDT therapy of mouse tumors, which can be effectively used for targeted enrichment and activation of tumor micro-acid environments. The results show that this NIR-II photosensitizer generates ROS through tumor micro-acid environment stimulation and laser triggering, showing precise tumor imaging guidance and significant tumor growth inhibition.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 315-328"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147080","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":"Structural connectivity and bioactivity in sol–gel silicate glass design","authors":"Chisokwuo Akunna,&nbsp;Marta Cerruti","doi":"10.1016/j.actbio.2024.08.030","DOIUrl":"10.1016/j.actbio.2024.08.030","url":null,"abstract":"<div><div>Bioactive glasses (BGs) bond with bone by forming hydroxy carbonate apatite (HCA) upon reaction in physiological fluid, a phenomenon known as bioactivity. BGs structural network connectivity determines their bioactivity. Sol–gel BGs are synthesized through the hydrolysis and condensation of metal alkoxide precursors in the presence of a catalyst, in aqueous environments. Several sol–gel synthesis parameters directly impact BG network connectivity: pH (i.e. acid or basic catalysis), water to alkoxide ratio (R_w), alkoxide type and presence of dopant ions. However, the relationship between bioactivity and these parameters remains surprisingly unexplored.</div><div>This study highlights the relationship between synthesis pH, R_w, network connectivity and bioactivity in silica-based sol-gel BGs and BGs doped with titanium (Ti) ions (TiBGs), the latter selected for their known ability to enhance network connectivity. BGs and TiBGs are synthesized with various R_w values under acidic and basic conditions, and their bioactivity is assessed in simulated body fluid for 7 days.</div><div>Increasing R_w decreases network connectivity and increases bioactivity of BGs with high network connectivity, as observed for base-catalyzed BGs and for both acid and base catalyzed TiBGs, but not in BGs with lower connectivity as evidenced in acid-catalyzed BGs. Basic catalysis of TiBGs prevents crystalline TiO₂ domain formation, which was instead consistently observed in TiBGs synthesized under acidic catalysis.</div><div>These findings help the design of BGs for applications where ion release needs to be enhanced even in the presence of dopants that slow down HCA formation, and of BGs with specific properties, e.g. TiO₂-containing BGs with potential bactericidal activity.</div></div><div><h3>Statement of significance</h3><div>Bioactive glasses (BGs) bond with bone by dissolving and forming hydroxycarbonate apatite (HCA) on their surface, offering applications in medicine and dentistry. BG's network connectivity influences its dissolution rate, and hence HCA formation. While solution-gelation (sol-gel) is commonly used for BG production, the effect of sol gel synthesis parameters on HCA formation remains unexplored. We studied the relationship between synthesis parameters (water-to-alkoxide ratio (R_w), catalyst, and dopant ions, particularly titanium), BG network connectivity, and HCA formation. We find that increasing R_w with any catalyst enhances HCA formation, particularly in glasses with high network connectivity. This understanding allows tailoring BG synthesis for different applications, e.g. those requiring doping with ions that increase network connectivity and fills a crucial gap in BG literature.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 374-392"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057489","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":"Automated data-driven discovery of material models based on symbolic regression: A case study on the human brain cortex","authors":"Jixin Hou ,&nbsp;Xianyan Chen ,&nbsp;Taotao Wu ,&nbsp;Ellen Kuhl ,&nbsp;Xianqiao Wang","doi":"10.1016/j.actbio.2024.09.005","DOIUrl":"10.1016/j.actbio.2024.09.005","url":null,"abstract":"<div><div>We introduce a data-driven framework to automatically identify interpretable and physically meaningful hyperelastic constitutive models from sparse data. Leveraging symbolic regression, our approach generates elegant hyperelastic models that achieve accurate data fitting with parsimonious mathematic formulas, while strictly adhering to hyperelasticity constraints such as polyconvexity/ellipticity. Our investigation spans three distinct hyperelastic models—invariant-based, principal stretch-based, and normal strain-based—and highlights the versatility of symbolic regression. We validate our new approach using synthetic data from five classic hyperelastic models and experimental data from the human brain cortex to demonstrate algorithmic efficacy. Our results suggest that our symbolic regression algorithms robustly discover accurate models with succinct mathematic expressions in invariant-based, stretch-based, and strain-based scenarios. Strikingly, the strain-based model exhibits superior accuracy, while both stretch-based and strain-based models effectively capture the nonlinearity and tension-compression asymmetry inherent to the human brain tissue. Polyconvexity/ellipticity assessment affirm the rigorous adherence to convexity requirements both within and beyond the training regime. However, the stretch-based models raise concerns regarding potential convexity loss under large deformations. The evaluation of predictive capabilities demonstrates remarkable interpolation capabilities for all three models and acceptable extrapolation performance for stretch-based and strain-based models. Finally, robustness tests on noise-embedded data underscore the reliability of our symbolic regression algorithms. Our study confirms the applicability and accuracy of symbolic regression in the automated discovery of isotropic hyperelastic models for the human brain and gives rise to a wide variety of applications in other soft matter systems.</div></div><div><h3>Statement of significance</h3><div>Our research introduces a pioneering data-driven framework that revolutionizes the automated identification of hyperelastic constitutive models, particularly in the context of soft matter systems such as the human brain. By harnessing the power of symbolic regression, we have unlocked the ability to distill intricate physical phenomena into elegant and interpretable mathematical expressions. Our approach not only ensures accurate fitting to sparse data but also upholds crucial hyperelasticity constraints, including polyconvexity, essential for maintaining physical relevance.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 276-296"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303127","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":"Nanoparticles target M2 macrophages to silence kallikrein-related peptidase 12 for the treatment of tuberculosis and drug-resistant tuberculosis","authors":"Yuanzhi Wang,&nbsp;Yiduo Liu,&nbsp;Meizhen Long,&nbsp;Yuhui Dong,&nbsp;Lin Li,&nbsp;Xiangmei Zhou","doi":"10.1016/j.actbio.2024.09.026","DOIUrl":"10.1016/j.actbio.2024.09.026","url":null,"abstract":"<div><div>Matrix metalloproteinases (MMPs) are involved in the breakdown of lung extracellular matrix and the consequent release of <em>Mycobacterium tuberculosis</em> into the airways. Recent studies indicate that kallikrein-related peptidase 12 (KLK12) regulate MMP-1 and MMP-9, suggesting that targeting the KLK12 gene could be a promising tuberculosis (TB) treatment. To maximise therapeutic potential, this strategy of silencing KLK12 needs to be delivered to the pathogenic cell population while preserving the immunoprotective and tissue homeostatic functions of other lung macrophages. Our research found that KLK12 is highly expressed in M2 macrophages, leading us to design mannose-based bovine serum albumin nanoparticles (MBNPs) for delivering siRNA to silence KLK12 in these cells. The results of <em>in vitro</em> experiments showed that MBNPs could accurately enter M2 macrophages and sustainably release KLK12-siRNA with the help of mannose and mannose receptor targeting. The results of the <em>in vivo</em> experiments showed that MBNPs could reach the lungs within 1 h after intraperitoneal injection and peaked at 6 h. MBNPs increased collagen fibre content in the lungs by decreasing the levels of KLK12/MMPs thereby limiting the progression of TB. Importantly, MBNPs provided greater alleviation of pulmonary TB symptoms and reduced bacterial load in both TB and drug-resistant TB models. These findings provide an alternative and effective option for the treatment of TB, especially when drug resistance occurs.</div></div><div><h3>Statement of significance</h3><div>RNA interference using small interfering RNA (siRNA) can target various genes and has potential for treating diseases such as tuberculosis (TB). However, siRNAs are unstable in the blood and within cells. This study presents bovine serum albumin nanoparticles encapsulating KLK12-siRNA (BNPs) synthesized via desolvation. A mannose layer was added (MBNPs) to target mannose receptors on M2 macrophages, facilitating endocytosis. The low pH-responsive MBNPs enhance lysosomal escape for siRNA delivery, downregulating the KLK12 pathway. Tests confirmed that MBNPs effectively inhibited <em>Mycobacterium bovis</em> proliferation, reduced granulomas, and decreased inflammation in a mouse model. This research aims to reduce antibiotic use, shorten treatment duration, and provide a novel TB treatment option.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 358-373"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303136","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":"In-situ hydrogen-generating injectable short fibers for osteoarthritis treatment by alleviating oxidative stress","authors":"Libin Pang ,&nbsp;Lei Xiang ,&nbsp;Gang Chen ,&nbsp;Wenguo Cui","doi":"10.1016/j.actbio.2024.09.008","DOIUrl":"10.1016/j.actbio.2024.09.008","url":null,"abstract":"<div><div>Hydrogen (H₂) has great potential in the treatment of osteoarthritis, but its rapid diffusion and short retention time make it difficult to exert stable therapeutic effects. This study developed a short-fiber injectable material that can continuously generate hydrogen <em>in situ</em> to eliminate reactive oxygen species (ROS), alleviate oxidative stress and inflammation, and promote tissue repair. We prepared H–Si nanosheets with high hydrogen generation efficiency using a wet chemical exfoliation method and combined them with GelMA short fibers via electrospinning technology, achieving the <em>in situ</em> delivery of H–Si nanosheets and regulated hydrogen generation rate through the encapsulation and degradation of GelMA, ultimately achieving continuous and controlled hydrogen supply and stable therapeutic effects for osteoarthritis. <em>In vitro</em> and <em>in vivo</em> experiments confirmed the safety and efficacy of this material. The results showed that the material could continuously and efficiently generate hydrogen in simulated physiological environments (100 mg of material could generate 8.6 % hydrogen), effectively eliminate cellular reactive oxygen species (ROS positive rate reduced by 85.89 %), reduce cellular senescence and apoptosis (cell death rate decreased by 52 %, SA-βgal expression decreased by 78.3 %), promote normal chondrocyte function (Col II expression increased by 67.4 %, Ki67 expression increased by 87.5 %), and improve osteoarthritis in rats (OARSI score increased by 216 %). The <em>in situ</em> hydrogen generation and control system designed in this study provides a new method for the hydrogen's local and stable treatment of osteoarthritis.</div></div><div><h3>Statement of significance</h3><div>Hydrogen (H₂) has great potential in the treatment of osteoarthritis by alleviating oxidative stress, but its rapid diffusion and short retention time make it difficult to exert stable therapeutic effects. This study introduces an innovative injectable material combining H–Si nanosheets and GelMA short fibers to address this issue. By enabling continuous <em>in situ</em> hydrogen generation, this material effectively eliminates reactive oxygen species, reduces oxidative stress and inflammation, and promotes tissue repair. <em>In vitro</em> and <em>in vivo</em> experiments demonstrate its high hydrogen generation efficiency, safety, and therapeutic efficacy, offering a promising new approach for osteoarthritis management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 406-419"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303133","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":"Engineered myovascular tissues for studies of endothelial/satellite cell interactions","authors":"Torie Broer ,&nbsp;Nick Tsintolas ,&nbsp;Karly Purkey ,&nbsp;Stewart Hammond ,&nbsp;Sophia DeLuca ,&nbsp;Tianyu Wu ,&nbsp;Ishika Gupta ,&nbsp;Alastair Khodabukus ,&nbsp;Nenad Bursac","doi":"10.1016/j.actbio.2024.09.020","DOIUrl":"10.1016/j.actbio.2024.09.020","url":null,"abstract":"<div><div>In native skeletal muscle, capillaries reside in close proximity to muscle stem cells (satellite cells, SCs) and regulate SC numbers and quiescence through partially understood mechanisms that are difficult to study <em>in vivo</em>. This challenge could be addressed by the development of a 3-dimensional (3D) <em>in vitro</em> model of vascularized skeletal muscle harboring both a pool of quiescent SCs and a robust network of capillaries. Still, studying interactions between SCs and endothelial cells (ECs) within a tissue-engineered muscle environment has been hampered by the incompatibility of commercially available EC media with skeletal muscle differentiation. In this study, we first optimized co-culture media and cellular ratios to generate highly functional vascularized human skeletal muscle tissues (“myovascular bundles”) with contractile properties (∼10 mN/mm²) equaling those of avascular, muscle-only tissues (“myobundles”). Within one week of muscle differentiation, ECs in these tissues formed a dense network of capillaries that co-aligned with muscle fibers and underwent initial lumenization. Incorporating vasculature within myobundles increased the total SC number by 82%, with SC density and quiescent signature being increased proximal (≤20μm) to EC networks. <em>In vivo</em>, at two weeks post-implantation into dorsal window chambers in nude mice, vascularized myobundles exhibited improved calcium handling compared to avascular implants. In summary, we engineered highly functional myovascular tissues that enable studies of the roles of EC-SC crosstalk in human muscle development, physiology, and disease.</div></div><div><h3>Statement of significance</h3><div>In native skeletal muscle, intricate relationships between vascular cells and muscle stem cells (“satellite cells”) play critical roles in muscle growth and regeneration. Current methods for <em>in vitro</em> engineering of contractile skeletal muscle do not recreate capillary networks present <em>in vivo</em>. Our study for the first time generates <em>in vitro</em> robustly vascularized, highly functional engineered human skeletal muscle tissues. Within these tissues, satellite cells are more abundant and, similar to <em>in vivo</em>, they are more dense and less proliferative proximal to endothelial cells. Upon implantation in mice, vascularized engineered muscles show improved calcium handling compared to muscle-only implants. We expect that this versatile <em>in vitro</em> system will enable studies of muscle-vasculature crosstalk in human development and disease.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 65-78"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303130","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}