Acta Biomaterialia最新文献

{"title":"Human bone ultrastructure in 3D: Multimodal correlative study combining nanoscale X-ray computed tomography and quantitative polarized Raman spectroscopy","authors":"Tatiana Kochetkova ,&nbsp;Tatiana Kormilina ,&nbsp;Silvan Englisch ,&nbsp;Dominik Drobek ,&nbsp;Benjamin Apeleo Zubiri ,&nbsp;Oliver Braun ,&nbsp;Michel Calame ,&nbsp;Stefan Remund ,&nbsp;Beat Neuenschwander ,&nbsp;Johann Michler ,&nbsp;Philippe Zysset ,&nbsp;Erdmann Spiecker ,&nbsp;Jakob Schwiedrzik","doi":"10.1016/j.actbio.2025.03.045","DOIUrl":"10.1016/j.actbio.2025.03.045","url":null,"abstract":"<div><div>Unique mechanical properties of cortical bone are defined by the arrangement and ratio of its organic and inorganic constituents. This arrangement can be influenced by ageing and disease, urging the understanding of normal and deviant morphological patterns down to the nanoscale level, as much as the exploration of techniques able to grant that knowledge. Here, the ultrastructure and composition of seven samples taken from the femoral neck cortical bone of a single donor (52 y.o. female, no metabolic bone disease) is assessed with emerging characterization techniques. Laboratory-based nanoscale X-ray computed tomography providing ∼50 nm spatial resolution at (16 nm)³ voxel size resolves not only the lacuno-canalicular network but also the mineral ellipsoids associated with mineralized collagen fibrils (MCF). Site-matching 3D data with quantitative polarized Raman spectroscopy provides, in turn, complementary information on relative mineral and organic composition, while both techniques allow to quantify the MCF orientation. Bone matrix composition and lacuna-canalicular network organization are shown to vary between the osteonal and interstitial zones. Both plywood and gradual oscillating motifs of bone lamellation are observed, in line with existing theories. By combining these two methods, future studies can concentrate on other bone ultrastructural units of interest like interlamellar and cement interfaces, the structure of MCF around lacunae and near Haversian channels, as well as the influence of metabolic diseases on bone ultrastructure.</div></div><div><h3>Statement of significance</h3><div>This study provides new insights into bone hierarchical organization, revealing local composition and lacuno-canalicular network organization within osteonal and interstitial bone zones, as well as their mineralized collagen fiber (MCF) orientation within the lamella. Synchrotron-like resolution was achieved on a laboratory-based nano-CT by exposing the volumes of interest from the bulk sample and applying machine learning segmentation algorithms. Site-matched analysis with quantitative Polarized Raman spectroscopy (qPRS) provided indirect access to relative mineral and organic composition variations and local MCF out-of-plane angle, with good agreement between the two methods. The proposed correlative experiment workflow greatly facilitates the characterization of bone ultrastructure and can be applied to other fields dealing with ordered hierarchical materials of similar feature sizes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 302-318"},"PeriodicalIF":9.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744604","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":"Advances in nanodelivery systems based on apoptosis strategies for enhanced rheumatoid arthritis therapy","authors":"Zongquan Zhang ,&nbsp;Yilin Liu ,&nbsp;Xiaoya Liang ,&nbsp;Qian Wang ,&nbsp;Maochang Xu ,&nbsp;Xi Yang ,&nbsp;Jun Tang ,&nbsp;Xinghui He ,&nbsp;Yufeng He ,&nbsp;Dan Zhang ,&nbsp;Chunhong Li","doi":"10.1016/j.actbio.2025.03.043","DOIUrl":"10.1016/j.actbio.2025.03.043","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder primarily characterized by persistent synovial inflammation and progressive bone erosion. The pathogenesis of RA involves a complex cascade of cellular and molecular events, including sustained hyperactivation of macrophages, excessive recruitment and activation of neutrophils, pathological proliferation and invasion of fibroblast-like synoviocytes (FLS), and dysregulated differentiation and function of osteoclasts (OCs). The inflammatory factors secreted by these dysregulated cells significantly disrupt the joint microenvironment through multiple pathological mechanisms, primarily by promoting synovial inflammation, cartilage matrix degradation, osteoclast-mediated bone erosion, and pathological angiogenesis. Therapeutic strategies targeting the induction of apoptosis in these malignant cells have demonstrated considerable potential in preclinical studies, offering a promising approach to enhance treatment outcomes by simultaneously reducing inflammatory cytokine production and inhibiting pathogenic cell proliferation. However, conventional therapeutic drugs are limited in clinical applications because of their high toxicity and side effects. Inflammation induces morphological and functional changes in cells within the rheumatoid arthritis microenvironment (RAM), particularly the overexpression of specific receptors on cell membranes. This phenomenon has driven the development of ligand-modified targeted nanodelivery systems (NDSs), which can specifically target and induce apoptosis in specific cell types, thereby enhancing therapeutic efficacy. This paper comprehensively reviews the research progress of targeted NDSs based on apoptosis strategies for RA therapy, with a detailed discussion of their advantages in inducing apoptosis in various disease-associated cells. Furthermore, the potential of combining apoptosis of multiple cell types for RA treatment is explored. This review is expected to improve insights into the apoptosis of malignant cells to enhance RA therapy.</div></div><div><h3>Statement of Significance</h3><div>This review highlights recent advances in nanodelivery systems (NDSs) based on apoptotic strategies for enhanced rheumatoid arthritis (RA) therapy. Unlike conventional NDSs, these optimized systems specifically induce apoptosis in malignant cells within the RA microenvironment by integrating multiple therapeutic strategies. By summarizing the latest research, our work demonstrates the potential of these NDSs to suppress inflammatory responses and prevent bone destruction through targeted elimination of malignant cells, offering a novel direction for RA treatment. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective therapeutic approaches for RA and other chronic inflammatory diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 87-103"},"PeriodicalIF":9.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744597","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":"Evaluating the single crystallinity of sea urchin calcite","authors":"Sebastian Hoerl ,&nbsp;Erika Griesshaber ,&nbsp;Antonio G. Checa ,&nbsp;Aimo Winkelmann ,&nbsp;Frank Förster ,&nbsp;Osama Alsheikha ,&nbsp;Felix Hidalgo ,&nbsp;Elena Sturm ,&nbsp;Sandro Jahn ,&nbsp;Wolfgang W. Schmahl","doi":"10.1016/j.actbio.2025.03.044","DOIUrl":"10.1016/j.actbio.2025.03.044","url":null,"abstract":"<div><div>Recent advancements in electron backscatter diffraction (EBSD) data evaluation enable the determination of misorientation between crystals below 0.1°, while with conventional EBSD data evaluation, the smallest misorientation precision between crystals scatters between 0.5°-1°. Sea urchin tests and spines are lightweight biomaterials with a serrated microstructure comprising interlinked calcite crystals. We investigated the microstructure and crystallographic texture of <em>Cidaris cidaris</em> and <em>Paracentrotus lividus</em> test and spine calcite with advanced EBSD measurement and data evaluation. In particular, we re-evaluated the widely accepted single-crystallinity of sea urchin calcite. We found that the test and the spines comprise calcite crystals with different fabrics and a significant variation in crystal co-orientation strength. Even the highly co-oriented calcite of <em>C. cidaris</em> and <em>P. lividus</em> is not perfectly single-crystalline. We found test and spine portions that feature significant internal misorientations (1-3°). Test c-axis orientation in <em>C. cidaris</em> is tangential to the outer test surface, while in the spines, it is parallel to the morphological axis of the spine. Primary and secondary spines feature a bimodal crystal texture comprising co-oriented calcite surrounded by a cortex of misoriented crystals. Crystal misorientation in the spine cortex seems to result mainly from competitive growth determinants. Deciphering the degree of crystallinity and mode of crystal organisation of biological hard tissues is vital for understanding their exceptional control of structure, material architecture and material properties.</div></div><div><h3>Statement of significance</h3><div>Echinoids form lightweight biomineralised skeletal elements with outstanding material properties and a complex microstructure formed of interlinked calcite crystals. The degree of crystallinity and the crystallographic organisation of the calcitic tests and spines are still under debate. We investigate and discuss the crystallinity, microstructure, and texture of <em>Cidaris cidaris</em> and <em>Paracentrotus lividus</em> test and spine crystals. Unprecedented and not yet used for biomineralised carbonate tissues, we apply electron backscatter diffraction pattern matching data evaluation, enabling detection of misorientation precision below 0.1°, relative to 0.5°-1° misorientation precision obtained from conventional EBSD data evaluation. We demonstrate that sea urchin test plates and spines are not single crystals. They feature internal small-angle misorientations and poorly co-oriented, polycrystalline regions with intricate microstructures.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 334-355"},"PeriodicalIF":9.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744602","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":"Development and calibration of digital twins for human skin growth in tissue expansion","authors":"Joel Laudo ,&nbsp;Tianhong Han ,&nbsp;Ariel E. Figueroa ,&nbsp;Joanna Ledwon ,&nbsp;Arun K. Gosain ,&nbsp;Taeksang Lee ,&nbsp;Adrian Buganza Tepole","doi":"10.1016/j.actbio.2025.03.026","DOIUrl":"10.1016/j.actbio.2025.03.026","url":null,"abstract":"<div><div>Tissue expansion (TE), an essential technique in reconstructive surgery, leverages the growth of skin in response to stretch. However, human skin growth dynamics have not been evaluated in vivo. Previously, we quantified this process in a porcine model and developed a calibrated computational framework. Here, we create patient-specific finite element (FE) models of skin growth in TE using longitudinal 3D photos collected during TE treatment. These geometries enable Bayesian model calibration, accounting for uncertainties in boundary conditions, mechanical properties, and biological parameters. The framework incorporates prior knowledge from the porcine model as well as literature information on human skin mechanics. The likelihood function assesses alignment between predicted and observed geometries, and predicted and observed skin growth. To efficiently sample the posterior distribution, we use Markov Chain Monte Carlo (MCMC) with Gaussian process surrogates, reducing computational cost. This pipeline is demonstrated in five TE cases. Post-calibration, FE models closely match 3D photos, with errors below 2 mm on average. Notably, Bayesian calibration collapses the critical stretch parameter posterior distribution. This study presents the first in vivo measurement of human skin growth, confirming that FE models accurately capture TE in the clinical setting, and that porcine-derived parameters provide a strong prior for Bayesian calibration in the clinical case. These findings support the development of personalized digital twins for TE, enhancing surgical planning and outcomes.</div><div><strong>Statement of significance</strong></div><div>Tissue expansion (TE) is widely used in reconstructive surgery, particularly for breast reconstruction and pediatric defect repair. While skin growth has been quantified in animal models, this work provides the first clinical measurement of human skin growth during TE. We employ a Bayesian calibration framework to create personalized finite element (FE) simulations for five TE cases. The initial FE model is constructed from a patient’s 3D photo taken at the start of treatment. Then, uncertainties in mechanical and biological parameters as well as boundary conditions are sampled and the model run. We use Gaussian process surrogates to replace the FE model. Calibration of parameters is done with 3D photos taken longitudinally during TE. This pipeline for skin digital twins can enhance personalized TE procedures, optimizing outcomes and reducing complications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 267-280"},"PeriodicalIF":9.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733540","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":"Recent advances in blood-brain barrier-on-a-chip models","authors":"Johanna Vetter ,&nbsp;Ilaria Palagi ,&nbsp;Ari Waisman ,&nbsp;Andreas Blaeser","doi":"10.1016/j.actbio.2025.03.041","DOIUrl":"10.1016/j.actbio.2025.03.041","url":null,"abstract":"<div><div>The blood-brain barrier is a physiological barrier between the vascular system and the nervous system. Under healthy conditions, it restricts the passage of most biomolecules into the brain, making drug development exceedingly challenging. Conventional cell-based in vitro models provide valuable insights into certain features of the BBB. Nevertheless, these models often lack the three-dimensional structure and dynamic interactions of the surrounding microenvironment, which greatly influence cell functionality. Consequently, considerable efforts have been made to enhance in vitro models for drug development and disease research. Recently, microfluidic organ-on-a-chip systems have emerged as promising candidates to better mimic the dynamic nature of the BBB. This review provides a comprehensive overview of recent BBB-on-chip devices. The typical building blocks, chip designs, the perfusion infrastructure, and readouts used to characterize and evaluate BBB formation are presented, analyzed, and discussed in detail.</div></div><div><h3>Statement of Significance</h3><div>The blood-brain barrier (BBB) is a highly selective barrier that controls what can enter the brain. While it protects the brain from harmful substances, it also hinders the delivery of treatments for neurological diseases such as Alzheimer's and Parkinson's. Due to its complexity, studying the BBB in living organisms remains difficult. However, recent advances in “organ-on-a-chip” technology have allowed scientists to create small, engineered models that replicate the BBB. These models provide a powerful platform to study diseases and test potential drugs with greater accuracy than traditional methods. Organ-on-a-chip devices are designed to mimic the behavior of organs or tissues in the human body, offering a more realistic and controlled environment for research. This review highlights recent breakthroughs in BBB-on-a-chip technology, showing how these models enhance current research and have the potential to transform the way we study brain diseases and develop new drugs. By integrating biology and engineering, BBB-on-a-chip technology has the potential to transform neuroscience research, improve drug development, and enhance our understanding of brain disorders.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 1-28"},"PeriodicalIF":9.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702339","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":"Early collagen degeneration in the temporomandibular intradiscal junction portends the onset of discal pathogenesis","authors":"Jiahao Zhou ,&nbsp;Liang Xie ,&nbsp;Jie Zhang,&nbsp;Xinyi Deng,&nbsp;Haozhe Chen,&nbsp;Songsong Zhu,&nbsp;Nan Jiang","doi":"10.1016/j.actbio.2025.03.021","DOIUrl":"10.1016/j.actbio.2025.03.021","url":null,"abstract":"<div><div>The temporomandibular intradiscal junction is a structural transition region connecting anteroposterior and circumferential aligned collagens fibers in the temporomandibular joint disc. Despite inherent stiffness, this region is incredibly susceptible to perforation under pathological conditions. This study aimed to determine whether the intradiscal junction was the initiation destructive site for discal degeneration. Utilizing high-resolution microscopy and nanoindentation, we characterized the structural and mechanical properties of the intradiscal junction. In rabbit models of anterior disc displacement-mediated temporomandibular osteoarthritis, we observed a significant reduction in collagen fibril diameter and an increase in denatured procollagen within the intradiscal junction as early as one week post-surgery, further spreading across the whole disc. Mass spectrometry proteomics showed that the alteration of the intradiscal junction was the consequence of mechanical stimuli mediated by tenascin-C and metalloproteinase-3. Notably, these degenerative changes were blocked by early reduction of the discal position. In vitro monotonic loading confirmed the dominant contribution of the intradiscal junction to the overall mechanical function of the disc. The present findings underscore the pivotal role of the intradiscal junction in the pathogenesis of discal degeneration, providing early detection indicators and therapeutics.</div></div><div><h3>Statement of significance</h3><div>Temporomandibular joint osteoarthritis (TMJOA) is a prevalent disorder affecting the structure and mechanics of the TMJ disc, with no effective early detection or treatment strategies. This study identifies the temporomandibular intradiscal junction (IJ) as the site where discal pathogenesis begins. Degeneration at the IJ involves reduced collagen fibril diameter and denatured procollagens, compromising the mechanical properties of the entire disc. Rescuing the IJ's position through TMJ anchorage surgery may restore mechanosensitive homeostasis and prevent further discal degeneration. These findings highlight the importance of the IJ in the discal progression, payving the way for early detection methods and treatment strategies that target aberrant remodeling in this critical region to slow or reverse disease.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 283-293"},"PeriodicalIF":9.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694777","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":"Enhancing the biocompatibility of phakic intraocular lens via selective fibronectin trapping","authors":"Yueze Hong ,&nbsp;Jianyu Xin ,&nbsp;Peng Wang ,&nbsp;Yanhong Song ,&nbsp;Xiangling Fan ,&nbsp;Li Yang ,&nbsp;Gaoyang Guo ,&nbsp;Daihua Fu ,&nbsp;Yan Dai ,&nbsp;Fanjun Zhang ,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2025.03.039","DOIUrl":"10.1016/j.actbio.2025.03.039","url":null,"abstract":"<div><div>Myopia has become a significant public health problem in recent decades, resulting in a profound public health and financial burden. The phakic intraocular lens (PIOL) utilized in myopia intraocular refractive surgery is constantly facing challenges in terms of uveal biocompatibility. Inspired by the “sandwich theory”, this study proposes the hypothesis that fibronectin (FN) can improve biocompatibility, and then creatively constructs a selective in-situ trap FN strategy. Specifically, PIOL surfaces with amide bonds covalently linking collagen were prepared, where selectivity was achieved by specific binding of collagen to FN. The obtained collagen modified material reduces immune response by reducing M1 polarization of macrophages, and its functionality and safety have been verified in vitro and in vivo. The grafting of collagen on the PIOL surface was able to occupy adsorption sites and inhibit the non-specific adsorption of other proteins while mimicking the extracellular matrix (ECM) microenvironment, further reducing the foreign body rejection. Overall, this strategy helps to address the issue of uveal biocompatibility in PIOL from a material design perspective, providing more economical and diversified options for patients with surgical needs.</div></div><div><h3>Statement of significance</h3><div>1. A phakic intraocular lens material with high ocular biocompatibility has been prepared. 2. By introducing acrylic anhydride and activating it, collagen is covalently grafted onto the surface of HEMA without altering its structure. 3. By utilizing the collagen binding domain in the structure of fibronectin, selective adsorption of fibronectin is enhanced, forming extracellular matrix analogs that reduce macrophage M1 polarization and lower inflammation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 240-255"},"PeriodicalIF":9.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694781","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":"Bioactive Peptide-Based Composite Hydrogel for Myocardial Infarction Treatment: ROS Scavenging and Angiogenesis Regulation","authors":"Qiuhao Luo ,&nbsp;Zhanshan Gao ,&nbsp;Long Bai ,&nbsp;Haolong Ye ,&nbsp;Haonan Ye ,&nbsp;Yue Wang ,&nbsp;Yue Gao ,&nbsp;Tianzi Chen ,&nbsp;Haijin Chen ,&nbsp;Yin Liu ,&nbsp;Li Yang ,&nbsp;Cheng Hu ,&nbsp;Dongdong Wu ,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2025.03.035","DOIUrl":"10.1016/j.actbio.2025.03.035","url":null,"abstract":"<div><div>After myocardial infarction (MI), the affected area of the myocardium falls into a state of ischemia and hypoxia, and subsequently, cardiomyocytes undergo a series of pathological changes and eventually transform into scar tissue. Therefore, restoring blood perfusion and reducing reactive oxygen species (ROS) are essential to promote the repair process of damaged myocardium. Here, the MMP12 (YWDAW) peptide which has a good antioxidant effect in deep-sea fish muscle, and the KRX (MRPYDANKR) peptide which shows a pro-angiogenesis effect from mammalian endothelial genes, were utilized collaboratively and loaded into an injectable GelMA hydrogel to achieve minimally invasive implantation and long-term retention at the MI site. The incorporation of bioactive peptides builds a stable and efficient system, which in addition to effectively removing ROS and promoting angiogenesis, avoids cell apoptosis and inflammation in the long run, and effectively inhibits the process of myocardial fibrosis. Both <em>in vivo</em> and <em>in vitro</em> experiments have shown that the combination of two short peptides with anti-oxidation and angiogenesis therapy can eventually achieve rapid repair of damaged myocardial tissue. This study fully demonstrated that natural functional peptides have great potential in promoting the repair and regeneration of infarcted hearts.</div></div><div><h3>Statement of Significance</h3><div>We have successfully synthesized antioxidant and pro-angiogenic peptides, which were subsequently incorporated into an injectable hydrogel matrix. This bioactive hydrogel system demonstrates dual therapeutic functions, effectively scavenging ROS while promoting angiogenesis, thereby facilitating cardiac tissue repair. Notably, the chemical synthesis approach employed in peptide production establishes a robust foundation for scalable manufacturing and broad biomedical applications, particularly in cardiovascular therapeutics.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 167-183"},"PeriodicalIF":9.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694769","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":"Construction of anti-calcification small-diameter vascular grafts using decellularized extracellular matrix/poly (L-lactide-co-ε-caprolactone) and baicalin-cathepsin S inhibitor","authors":"Yanjiao Teng ,&nbsp;Xiaohai Zhang ,&nbsp;Lin Song ,&nbsp;Jianing Yang ,&nbsp;Duo Li ,&nbsp;Ziqi Shi ,&nbsp;Xiaoqin Guo ,&nbsp;Shufang Wang ,&nbsp;Haojun Fan ,&nbsp;Li Jiang ,&nbsp;Shike Hou ,&nbsp;Seeram Ramakrishna ,&nbsp;Qi Lv ,&nbsp;Jie Shi","doi":"10.1016/j.actbio.2025.03.033","DOIUrl":"10.1016/j.actbio.2025.03.033","url":null,"abstract":"<div><div>The long-term transplantation of small-diameter vascular grafts (SDVGs) is associated with a risk of calcification, which is a key factor limiting the clinical translation of SDVG. Hence, there is an urgency attached to the development of new SDVGs with anti-calcification properties. Here, we used decellularized extracellular matrix (dECM) and poly (L-lactide-co-ε-caprolactone) (PLCL) as base materials and combined these with baicalin, cathepsin S (Cat S) inhibitor to prepare PBC-SDVGs by electrospinning. Baicalin contains carboxyl and hydroxyl groups that can interact with chemical groups in dECM powder, potentially blocking calcium nucleation sites. Cat S inhibitor prevents elastin degradation and further reduces the risk of calcification. PBC-SDVGs were biocompatible and when implanted in rat abdominal aorta, accelerated endothelialization, enhanced vascular tissue regeneration, inhibited elastin degradation, and promoted macrophage polarization M2 phenotype to regulate inflammation. After 3 months of implantation, the results of Doppler ultrasound, MicroCT, and histological staining revealed a significant reduction in calcification. In summary, the developed anti-calcification SDVGs offer a promising strategy for long-term implantation with significant clinical application potential.</div></div><div><h3>Statement of Significance</h3><div>The dECM and PLCL were used as base materials, connected with baicalin, and loaded with Cat S inhibitor to prepare PBC-SDVGs. The baicalin and dECM powder formed hydrogen bonds to crosslink together reducing the calcium deposition. <em>In vitro</em>, the vascular graft downregulated the expression level of osteogenic genes and promoted macrophage polarization toward an anti-inflammatory M2 phenotype, thereby reducing calcification. The PBC-SDVGs implanted in rat abdominal aorta can accelerate endothelialization, enhance vascular tissue regeneration, inhibit elastin degradation, reduce inflammation response and calcification.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 184-201"},"PeriodicalIF":9.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694771","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":"Modulating biomechanical and integrating biochemical cues to foster adaptive remodeling of tissue engineered matrices for cardiovascular implants","authors":"Pascal Breitenstein ,&nbsp;Valery L. Visser ,&nbsp;Sarah E. Motta ,&nbsp;Marcy Martin ,&nbsp;Melanie Generali ,&nbsp;Frank P.T. Baaijens ,&nbsp;Sandra Loerakker ,&nbsp;Christopher K. Breuer ,&nbsp;Simon P. Hoerstrup ,&nbsp;Maximilian Y. Emmert","doi":"10.1016/j.actbio.2025.03.036","DOIUrl":"10.1016/j.actbio.2025.03.036","url":null,"abstract":"<div><div>Cardiovascular disease remains one of the leading causes of mortality in the Western world. Congenital heart disease affects nearly 1 % of newborns, with approximately one-fourth requiring reconstructive surgery during their lifetime. Current cardiovascular replacement options have significant limitations. Their inability to grow poses particular challenges for pediatric patients. Tissue Engineered Matrix (TEM)-based <em>in situ</em> constructs, with their self-repair and growth potential, offer a promising solution to overcome the limitations of current clinically used replacement options. Various functionalization strategies, involving the integration of biomechanical or biochemical components to enhance biocompatibility, have been developed for Tissue Engineered Vascular Grafts (TEVG) and Tissue Engineered Heart Valves (TEHV) to foster their capacity for <em>in vivo</em> remodeling. In this review, we present the current state of clinical translation for TEVG and TEHV, and provide a comprehensive overview of biomechanical and biochemical functionalization strategies for TEVG and TEHV. We discuss the rationale for functionalization, the implementation of functionalization cues in TEM-based TEVG and TEHV, and the interrelatedness of biomechanical and biochemical cues in the <em>in vivo</em> response. Finally, we address the challenges associated with functionalization and discuss how interdisciplinary research, especially when combined with <em>in silico</em> models, could enhance the translation of these strategies into clinical applications.</div></div><div><h3>Statement of significance</h3><div>Cardiovascular disease remains one of the leading causes of mortality, with current replacements being unable to grow and regenerate. In this review, we present the current state of clinical translation for tissue engineered vascular grafts (TEVG) and heart valves (TEHV). Particularly, we discuss the rationale and implementation for functionalization cues in tissue engineered matrix-based TEVGs and TEHVs, and for the first time we introduce the interrelatedness of biomechanical and biochemical cues in the <em>in-vivo</em> response. These insights pave the way for next-generation cardiovascular implants that promise better durability, biocompatibility, and growth potential. Finally, we address the challenges associated with functionalization and discuss how interdisciplinary research, especially when combined with <em>in silico</em> models, could enhance the translation of these strategies into clinical applications .</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 48-67"},"PeriodicalIF":9.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675034","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}