Acta biomaterialia最新文献

{"title":"Bone mineral tessellation: Atomic force microscopy of the volume-filling mineralization pattern in hydrated and dehydrated states.","authors":"Valentin Nelea, Eran Ittah, Marc D McKee, Natalie Reznikov","doi":"10.1016/j.actbio.2025.05.016","DOIUrl":"10.1016/j.actbio.2025.05.016","url":null,"abstract":"<p><p>Bone is a specialized hard connective tissue with a hierarchical organization of its components. At the micrometer scale, mineral entities of roughly uniform shape tessellate in 3D within an organized, crosslinked and hydrated scaffold of mostly type I collagen. Here we report on the visualization by atomic force microscopy (AFM) of the volume-filling mineralization pattern of tesselles in lamellar bone, in hydrated and dehydrated conditions (for human, bovine, porcine and ovine bone). Microscale mineral tessellation was clearly visible when bulk lamellar bone was hydrated, whereas dry bone showed submicron nanogranularity instead of tesselle boundaries. Time-lapse AFM experiments of gradual passive dehydration of bone revealed topographical changes for all bone species with the tessellation appearance vanishing after two weeks of dehydration. AFM adhesion forces dropped within the first days of dehydration in all bone species, indicating that surface stickiness is more sensitive to passive dehydration than is stiffness. Irrespective of the bone species, AFM stiffness measurements found that hydrated bone was more compliant than dehydrated bone. AFM Young's modulus measurements of more recently formed osteonal lamellae intersecting with older interstitial lamellae found that the modulus in both hydrated and dehydrated states was lower in the osteonal lamellae. Modelling of water sorption to the surface of stochiometric hydroxyapatite showed that the presence of rigid hydration shells delineates the tesselle boundaries and smoothens the nanogranularity, confirming the AFM observations. This study highlights the importance of regarding water as a fundamental architecting component of bone. STATEMENT OF SIGNIFICANCE: Here we report on visualization of the mineral tessellation pattern in lamellar bone by atomic force microscopy (AFM) in hydrated and dehydrated conditions. We show that lamellar bone (human, bovine, porcine and ovine) contains a universal volume-filling mineral tessellation. The visibility of the tessellation pattern by AFM strongly depends on the state of bone hydration. Modelling water sorption to the surface of stochiometric hydroxyapatite indicated that mechanical and morphological characteristics of lamellar bone (e.g., stiffness, adhesion, contours of tesselle boundaries) can be attributed to the presence of rigid hydration shells. This study highlights the importance of water incorporation as a fundamental component of bone, on par with the mineral and the organic extracellular matrix.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014815","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":"IL-21R-Targeted Nano-immunosuppressant Prevents Acute Rejection in Allogeneic Transplantation by Blocking Maturation of T Follicular Helper Cells.","authors":"Xiandong Zeng, Yixiao Pan, Jiangtao Lin, Zhigang Zheng, Huimin Wu, Yining Wang, You Wu, Yufei Shen, Yujia Chen, Yifan Zhao, Qiang Xia, Yourong Duan, Kang He","doi":"10.1016/j.actbio.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.012","url":null,"abstract":"<p><p>During organ transplantation, immune rejection is a primary cause of graft failure. In the underlying pathophysiology of rejection, T follicular helper (Tfh) cells and interleukin-21 (IL-21) play pivotal roles. Tfh cells exacerbate the humoral immune response by promoting B cell differentiation and antibody production, which leads to damage of the transplanted tissue. IL-21, a key pro-inflammatory cytokine, binds to its receptor (IL-21R) to enhance both the growth and function of Tfh cells, while also further driving B cell activation and differentiation into plasma cells. Building on this knowledge, we have developed a tacrolimus-based nano-inhibitor designed to target Tfh cells. This nano-inhibitor is constructed using a mPEG-PLGA-PLL (PEAL) scaffold, with IL-21R monoclonal antibodies conjugated to its surface, and tacrolimus encapsulated within the structure. In vitro experiments demonstrated that this nano-inhibitor effectively targets Tfh cells, inhibiting the differentiation of naive CD4+ T cells into Tfh cells. In co-culture systems of T and B cells, it significantly suppresses the activation of both cell types, leading to a reduction in IgG antibody production. In vivo, the nano-inhibitor selectively targets secondary lymphoid organs, reduces systemic inflammation, minimizes lymphocyte infiltration into the graft, and induces immune tolerance toward the transplanted tissue. In addition, no significant toxicity was observed in vitro or in vivo. As a therapeutic agent that simultaneously modulates both T and B cell responses, we believe it holds significant promise for broader applications in transplantation immunotherapy. STATEMENT OF SIGNIFICANCE: This study presents a groundbreaking nano-immunosuppressant designed to target both T and B cells, addressing the critical challenge of acute rejection in allogeneic transplantation. By combining tacrolimus nanoparticles with IL-21 receptor antibodies, this immunosuppressant effectively suppresses Tfh cell proliferation and B cell activation, significantly reducing IgG generation. The formulation enhances tacrolimus's bioavailability, minimizes off-target toxicity, and overcomes its narrow therapeutic window. In vitro and in vivo studies show reduced lymphocyte infiltration, lower inflammatory markers, and decreased nephrotoxicity compared to conventional tacrolimus.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037176","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":"Electrohydrodynamically-printed Serpentine Fiber Scaffolds with Enhanced Conductivity and Elasticity for Post-Myocardial Infarction Repair.","authors":"Liyan Fu, Kang Han, Jie Qi, Qi Lei, Xiaomin Wang, Jinmin Wu, Na Yang, Ying Li, Yuming Kang, Xiaojing Yu, Liuyang Zhang, Mao Mao, Jiankang He","doi":"10.1016/j.actbio.2025.05.014","DOIUrl":"10.1016/j.actbio.2025.05.014","url":null,"abstract":"<p><p>Myocardial infarction remains a leading threat to cardiovascular health, with electrical conduction abnormalities in the infarcted myocardium significantly exacerbating cardiac dysfunction. Enhancing the conductive microenvironment in the infarcted region is essential for promoting myocardial repair. In this study, we developed gold-coated serpentine microfiber-based cardiac scaffolds using electrohydrodynamic printing, which mimicked the intricate architecture of the myocardial tissue's fibrous membrane and allowed for up to 20 % elastic deformation, similar to the maximum strain of the natural heart. Compared to uncoated serpentine scaffolds and traditional linear cardiac scaffolds, the gold-coated serpentine cardiac scaffolds demonstrated enhanced expression of myocardial-specific proteins, including connexin-43 and α-actinin, increased myocardial cell contraction frequency, and better mechanical compatibility with natural cardiac deformation. In a rat model of myocardial infarction, implantation of gold-coated serpentine cardiac scaffolds over four weeks provided significant mechanical support to the infarcted region, reduced myocardial hypertrophy, and markedly improved left ventricular remodeling and cardiac function. Collectively, our findings highlight the potential of serpentine conductive fiber scaffolds as a promising therapeutic strategy for post-myocardial infarction repair, offering innovative insights into the treatment of heart diseases. STATEMENT OF SIGNIFICANCE: This study introduces gold-coated serpentine microfiber scaffolds, created via electrohydrodynamic printing, as a promising solution for post-myocardial infarction repair. These scaffolds, designed to mimic the natural myocardial architecture, offer up to 20 % elastic deformation and enhanced electrical conductivity. Their superior mechanical properties, biocompatibility, and ability to support myocardial cell function make them a promising strategy for restoring heart function post-infarction.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048437","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":"Large animal model of controlled peripheral artery calcification.","authors":"Alexey Kamenskiy, Barbara Batista de Oliveira, Frazer Heinis, Pranav Renavikar, John Eberth, Jason MacTaggart","doi":"10.1016/j.actbio.2025.04.055","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.055","url":null,"abstract":"<p><p>Peripheral artery disease (PAD) in the lower extremity arteries leads to significant morbidity and mortality. Arterial calcification contributes to poor clinical outcomes and greatly increases the risk of amputation. Current treatments for calcific lesions are limited and yield suboptimal results. A large animal model that closely mimics calcific PAD and accommodates human-sized devices could enhance the development of safer and more effective therapies. Our objective was to create a swine model of late-stage arterial calcification to test the efficacy and side effects of surgical interventions. To induce lesions, swine received injections of CaCl₂ directly into the media and periadventitial spaces of the iliac, femoral, and popliteal arteries using a micro-needle catheter. The injection sites were varied to create eccentric and concentric lesions of differing lengths and patterns. Adjacent non-calcified arterial segments served as intersubject controls. The lesions were allowed to mature, and Computed Tomography Angiography and Intravascular Ultrasound imaging demonstrated ring-like calcification patterns and no pulsatility as early as 4 weeks after induction. Mechanical testing of excised arteries mirrored the mechanical properties of calcified human vessels, including characteristic stiffening. Histological analysis further confirmed that the calcified arteries in this model closely resembled human calcified femoropopliteal vessels, displaying inflammation, accumulation of collagen and glycosaminoglycans, elastin degradation, and smooth muscle cell loss within a degenerated tunica media. This porcine model replicates key pathological features of human calcific disease and provides a robust platform to evaluate the impacts and mechanisms of calcium-modifying treatments. STATEMENT OF SIGNIFICANCE: Arterial calcification is a key contributor to poor outcomes in peripheral artery disease (PAD). Our study presents a swine model of controlled peripheral artery calcification produced using targeted calcium chloride injections delivered endovascularly via a microneedle catheter. This approach creates arterial calcific lesions that closely replicate the mechanical, structural, and histological features of human calcified arteries. Additionally, the model accommodates human-sized devices, providing a robust platform for testing advanced biomaterials, devices, and therapies designed to modify or reverse calcification. By addressing a significant gap in preclinical research, our work aims to enhance treatment strategies for PAD, with the potential to reduce amputation rates and improve patient outcomes.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057874","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":"Integration of mechanics and immunology: Perspective for understanding fibrotic disease mechanisms and innovating therapeutic strategies.","authors":"Min Lei, Guobao Chen","doi":"10.1016/j.actbio.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.011","url":null,"abstract":"<p><p>The treatment of fibrotic diseases has long posed a medical challenge due to the complex mechanisms underlying their occurrence and progression. Emerging evidence suggests that fibrosis development is influenced not only by biochemical factors but also by the activation of mechanotransduction in response to mechanical stimuli. Mechanoimmunology, an interdisciplinary field that examines how the immune system is influenced by physical forces and mechanical environments, has recently demonstrated significant importance and considerable potential for application in the study of fibrotic diseases. While the mechanisms by which biochemical signals regulate the immune system have been extensively explored, the progression of fibrosis is often impacted by both immune dysregulation and mechanical changes. During fibrosis, immune cells encounter strong mechanical stimuli, such as stiffer substrates and altered viscoelasticity, which activate their own mechanotransduction pathways and subsequently influence fibrosis progression. Targeting the mechanosensation of immune cells to enhance or inhibit their mechanoreception and mechanotransduction, thereby enhancing the anti-fibrotic role they play in the fibrotic process, could help innovate therapeutic strategies for fibrotic diseases. STATEMENT OF SIGNIFICANCE: Fibrotic disease progression is often associated with dysregulation of both tissue mechanical properties and immune responses. The fibrotic microenvironment's altered mechanical properties both result from and drive fibrosis, while immune cells actively sense and respond to these mechanical cues through mechanotransduction pathways. Emerging mechanoimmunology research highlights how mechanical stimuli influence immune cell behavior, yet the precise regulatory mechanisms remain unclear. This review examines mechanical communication in fibrosis, focusing on immune cells' mechanosensing capabilities and their role in disease progression, which helps to enhance our understanding of the pathogenesis of fibrosis and inform innovative strategies to open up mechano-immune pathways targeting fibrosis therapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058669","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":"Simultaneous measurement of tensile and shear elasticity and anisotropy in human skeletal muscle tissue using steered ultrasound shear waves.","authors":"Ricardoj Andrade, Apolline Racapé, Mar Hernández-Secorún, Ha-Hien-Phuong Ngo, Alice Lemoine, Nicolas Etaix, Thomas Frappart, Christophe Fraschini, Jean-Luc Gennisson, Antoine Nordez","doi":"10.1016/j.actbio.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.010","url":null,"abstract":"<p><p>Load-bearing skeletal muscle tissues are reinforced by intricate networks of protein fibers aligned in preferential orientations, imparting direction-dependent mechanical properties (anisotropy). Characterizing this anisotropy in vivo is essential for understanding both normal and pathological muscle function, as well as structural integrity. However, current noninvasive techniques are limited in their ability to accurately measure the mechanical properties of anisotropic tissues such as skeletal muscle. Here, we used an innovative angle-resolved ultrasound elastography method, recently developed by our team, to simultaneously quantify tensile and shear elasticity and anisotropy, enabling comprehensive assessment of muscle biomechanics. We fully characterized the mechanical properties of the biceps brachii in fourteen healthy young adults under passive and active axial loadings, revealing distinct shear and tensile mechanical behaviors both along and across muscle fibers. Notably, tensile and shear moduli along the main fiber orientation were found to be uncoupled, while cross-muscle fiber measurements exhibited a consistent modulus ratio of 3.4 ± 0.2, regardless of axial loading conditions or intensities. These findings highlight the anisotropic nature of skeletal muscle and provide valuable insights into its in vivo mechanical behavior. Both shear and tensile anisotropy increased with muscle axial physiological loading, indicating that our method is sensitive to changes in anisotropic tissue mechanics. Lastly, we demonstrated that angle-resolved ultrasound shear wave elastography provides direct estimates of shear and tensile properties, offering significant promise for clinical applications, including neuromuscular disease diagnostics and monitoring, biomechanical modeling for predicting tissue responses to loading and therapies, and tissue engineering. STATEMENT OF SIGNIFICANCE: : Conventional ultrasound shear wave elastography techniques overlook the anisotropy of skeletal muscles, leading to incomplete tissue mechanical characterization. In this study, we leveraged an innovative angle-resolved elastography method to assess tensile and shear elasticity, along with their anisotropic factors, of human muscle in vivo. For the first time, we reveal the intricate relationships between tensile and shear elasticities during active and passive physiological loading. This technique enhances our understanding of muscle mechanics and has promising clinical implications for muscle health and neuromuscular disease management, where tissue structural and mechanical properties are often altered. Additionally, it could help in developing constitutive models for muscle tissue and contribute to the design of tissue-engineered materials.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065112","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":"Low-temperature plasma effect-induced enhancement of osteogenic activity in calcium phosphate ceramics.","authors":"Fengxiong Luo, Yu Yang, Dongxuan Li, Ruiqi Mao, Yawen Huang, Jian Lu, Xiangdong Zhu, Kefeng Wang, Yujiang Fan, Xingdong Zhang","doi":"10.1016/j.actbio.2025.04.048","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.048","url":null,"abstract":"<p><p>Calcium phosphate (Ca-P) ceramics are promising bioactive material that can be used for the remodeling and regeneration of bone tissue. However, it's sintering temperature-dependent mechanical strength, which is negatively correlated with its bioactivity, causes difficulties in improving the comprehensive performance of Ca-P ceramics. Here, the femtosecond laser (FSL) with low-temperature plasma effect was adopted to modify the hydroxyapatite (HA) ceramics after high temperatures (1250 °C) sintering, pursuing higher mechanical strength along with better osteogenic activity. The changes in the physicochemical properties of the materials and the osteogenic activity were characterized and investigated. Cell evaluations and in vivo experiments were performed to assess and verify the effect of FSL processing on the osteogenic capability of HA ceramics. The results indicated that α- and β-tricalcium phosphate (TCP) multiphase components were formed on the HA ceramic surfaces after laser treatment, simultaneously bringing about surface micro-nano porous structure, accelerated release of calcium (Ca) and phosphate (Pi) ions, enhancement of roughness, hydrophilicity and surface energy. Their synergistic effect facilitated apatite precipitation on the HA surface, promoted osteogenic differentiation and osteogenic/angiogenic gene expression. In vivo results also confirmed the enhancement of HA ceramic osteogenic activity by FSL treatment. This study presents an effective strategy of introducing FSL etching to high-temperature sintered Ca-P ceramics to improve the bone regeneration of HA ceramics and attain satisfactory mechanical strength at the same time. It will further promote the clinical application of HA ceramics in the field of bone regenerative repair. STATEMENT OF SIGNIFICANCE: This study introduces a method that uses the low-temperature plasma effect of the femtosecond laser (FSL) to modify the surfaces of high-temperature sintered hydroxyapatite (HA) ceramics, enhancing their osteogenic activity while maintaining the original mechanical strength. FSL processing induces the formation of bioactive multiphase of tricalcium phosphate (α-TCP and β-TCP) on the surfaces, creates micro-nano topographies, improves hydrophilicity and surface energy, promoting osteoblast differentiation and osteogenic gene expression for faster bone regeneration. This method overcomes the issue that high-temperature sintered HA ceramics have high strength but low osteogenic activity. It provides a modification method for HA ceramics with well-characterized performance enhancements, offering a convenient and effective strategy for high quality bone regenerative repair.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044690","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":"Emergence of Snail Mucus as a Multifunctional Biogenic Material for Biomedical Applications.","authors":"Pritha Sarkar, Disha Iyengar, Kausik Mukhopadhyay","doi":"10.1016/j.actbio.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.006","url":null,"abstract":"<p><p>Snails are mollusks or shelled gastropods found everywhere on Earth. Biologically, snail mucus can be described as a multifunctional natural polymeric gel with adhesive and antimicrobial properties, rendering it a promising ingredient in pharmaceutics and biomedical applications. These properties have been exploited in cosmetics and dermatology applications over the last few years. However, the exploration of snail mucus for other biomedical applications, e.g., wound healing and drug delivery, remains new and very promising. Against this backdrop, this review explores the potential of snail mucus for a wide spectrum of biomedical applications, ranging from wound healing to cancer treatment to regenerative engineering. It will be emphasized how its application in wound healing has gained traction owing to its antimicrobial and anti-inflammatory properties. Beyond wound care, snail mucus has been investigated as a drug delivery vehicle in treating diabetes and targeted cancer therapies. While further extensive research and clinical trials are needed to solidify the efficacy of snail mucus as a biomaterial, this review will shed light on the prospect of using snail mucus alone and in combination with other natural or synthetic biopolymers as soft materials for widespread biomedical applications. STATEMENT OF SIGNIFICANCE: Exploring snail mucus as a biomaterial across various fields, including oncology, drug delivery, cosmetics, antibacterial properties, and wound healing, presents a fascinating avenue for zootherapy research. This review provides an in-depth account of the recent developments in snail mucus' potential for a broad spectrum of biomedical applications, from wound healing to cancer treatment and regenerative engineering. It highlights the growing interest in mucus' use in wound healing, attributed to its antimicrobial and anti-inflammatory properties. It has also been investigated as a drug delivery vehicle for diabetes treatment and targeted cancer therapies. The impact of such research is significant, as it could lead to the creation of innovative biomaterials for a wide range of applications, revolutionizing the field of biomaterials.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045845","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":"Endogenous dysregulated energy and amino acid metabolism delay scaffold-guided large volume bone regeneration in a diabetic rat model with Leptin receptor deficiency.","authors":"Daniela B Dias, WingLee Chan, Agnes Ellinghaus, Raphaela Fritsche-Guenther, Janine Wiebach, André Bembennek, Tanja Laske, Jan Baumbach, Georg N Duda, Jennifer A Kirwan, Patrina S P Poh","doi":"10.1016/j.actbio.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.007","url":null,"abstract":"<p><p>Scaffold-guided bone regeneration (SGBR) offers a promising solution for treating large-volume bone defects. However, its efficacy in compromised healing environments, such as those associated with metabolic conditions like Type 2 Diabetes (T2D), remains poorly understood. This study evaluates the potential of 3D-printed polycaprolactone (PCL) scaffolds for large-volume bone regeneration in preclinical models simulating T2D-induced metabolic challenges. Our results reveal that scaffolds alone are insufficient to overcome the metabolic barriers to effective bone regeneration. Metabolomic analysis of regenerating tissue identified significant disruptions in key metabolic pathways involved in energy production and amino acid synthesis in T2D rats compared to controls. Notably, aconitic acid, ornithine, and glycine levels were elevated in non-diabetic conditions, whereas phosphoenolpyruvate was markedly increased under T2D conditions. Secondary harmonic generation (SHG) imaging further demonstrated impaired collagen organization within T2D regenerating tissue, correlating with disrupted collagen synthesis critical for bone matrix formation. In vitro, the exogenous supplementation of alpha-ketoglutarate (α-KG)-a crucial citric acid cycle intermediate-enhanced mineralized tissue formation in human adipose-derived mesenchymal stem cells (hAdMSCs) from T2D donors, achieving levels superior to non-T2D cells. These findings underscore the metabolic underpinnings of impaired bone regeneration in T2D. Optimized 3D printed scaffolds alone do not counterbalance the impaired regeneration in T2D. Here we highlight a therapeutic potential of metabolic supplementation to optimize SGBR outcomes. This study provides a critical foundation for advancing translational research and developing regenerative therapies tailored to high-risk metabolic disease populations. STATEMENT OF SIGNIFICANCE: Scaffold-guided bone regeneration (SGBR) holds great promise for addressing large bone defects, but its efficacy in metabolically challenged conditions like Type 2 Diabetes (T2D) remains limited. This study uses a metabolomics-driven approach to reveal how metabolic dysregulation in T2D, including disruptions in energy and amino acid pathways, impairs collagen organization and extracellular matrix (ECM) formation-critical for successful bone healing. By identifying α-ketoglutarate (α-KG) as a potential supplement to restore metabolic balance, this work offers novel insights into enhancing scaffold performance under compromised conditions. These findings provide a foundation for integrating bioactive compounds into scaffold designs, advancing personalized strategies in regenerative medicine, and addressing a critical gap in bone defect treatment for diabetic patients.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056029","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":"Optical Coherence Elastography Measures Mechanical Tension in the Lens and Capsule.","authors":"Xu Feng, Guo-Yang Li, Yuxuan Jiang, Owen Shortt-Nguyen, Seok-Hyun Yun","doi":"10.1016/j.actbio.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.009","url":null,"abstract":"<p><p>Lens tension is essential for accommodative vision but remains difficult to measure with precision. Here, we present an optical coherence elastography (OCE) technique that quantifies both tension and elastic modulus in the lens capsule and underlying tissue. This method derives mechanical parameters from surface wave dispersion across a critical frequency range of 1-30 kHz. Using isolated lenses from six-month-old pigs, we measured intrinsic anterior capsular tensions of 0-20 kPa and posterior capsular tensions of 40-50 kPa, induced by intra-lenticular pressure at the cortical surface. The mean shear moduli of anterior and posterior capsules were 630 kPa and 400 kPa, respectively, nearly 100-fold greater than that of the cortical tissues, where tensions were below 1 kPa. Biaxial zonular stretching (∼4% strain) increased anterior capsular tension by 67 kPa, with a low uncertainty of only 2 kPa. This optical method holds significant promise for diagnosing and managing accommodative dysfunctions through lens mechanics assessment in clinical settings. STATEMENT OF SIGNIFICANCE: Optical coherence elastography (OCE) is a rapidly advancing imaging modality, but its applications have been limited to stiffness measurements. This work represents a significant innovation by extending OCE capabilities to include force and stress quantification, broadening its potential applications in biomedical and clinical contexts. The ability to measure in situ capsular tension in the eye lens is a major breakthrough, as capsular tension is essential for transferring zonular fiber forces to the lens tissue during accommodation-a process critical for vision. This study provides quantitative insights into the mechanical mechanisms of accommodation and holds strong promise as a clinical tool for assessing lens tissue mechanics, addressing a capability gap in current clinical practice.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032028","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}