Acta Biomaterialia最新文献

{"title":"A biomimetic nanofiber composite hydrogel with tissue adhesion, self-healing and antibacterial ability for infected wound healing","authors":"Yinghao Tian ,&nbsp;Xiaogang Bao ,&nbsp;Shunmin Wang ,&nbsp;Chen Tang ,&nbsp;Nianqi Wu ,&nbsp;Guifei Li ,&nbsp;Kaixuan Ren ,&nbsp;Jingbo Yin ,&nbsp;Shifeng Yan ,&nbsp;Guohua Xu","doi":"10.1016/j.actbio.2025.04.002","DOIUrl":"10.1016/j.actbio.2025.04.002","url":null,"abstract":"<div><div>Skin injuries represent a significant clinical challenge, as conventional dressings frequently induce secondary trauma and microbial infiltration due to suboptimal barrier properties, ultimately delaying tissue repair. Ideal wound dressings should not only replicate the structure of native skin tissue but also create an environment conducive to cell viability. In this study, an injectable nanofiber composite self-healing hydrogel was developed for treating infected wounds. The antimicrobial properties of the hydrogel were achieved through the adsorption of branched polyethyleneimine (PEI) on gelatin fibers, while its self-healing capabilities were enhanced via Schiff base reactions and its tissue adhesion was strengthened by the incorporation of dopamine. Results demonstrated that the hydrogel exhibited strong biocompatibility and antimicrobial activity, promoted macrophage polarization towards the M2 phenotype, effectively suppressed inflammation, and facilitated wound healing in an infected wound model.</div></div><div><h3>Statement of significance</h3><div>Wound infections pose a significant clinical challenge, often impeding healing and, in severe cases, leading to ulceration or life-threatening complications. In this study, a gelatin nanofiber composite hydrogel (PGF@ALG/PLGA hydrogel) functionalized with branched polyethyleneimine (PEI) was developed to address infected wounds through a biomimetic structure and enhanced pro-healing properties. The gelatin nanofibers within the hydrogel matrix facilitated electrostatic immobilization of PEI, effectively mitigating its inherent cytotoxicity by restricting free cationic charge exposure while ensuring localized surface enrichment. The resulting hydrogel exhibited robust tissue adhesion and autonomous self-healing capability. In infected wound models, the PEI-modified nanofibers within PGF@ALG/PLGA hydrogels demonstrated obvious antibacterial efficacy and promoted macrophage polarization to the M2 phenotype, synergistically accelerating the transition from the inflammatory phase to tissue regeneration. These findings underscore the therapeutic potential of PGF@ALG/PLGA hydrogel as a multifunctional platform for managing chronic infected wounds.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 326-339"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788977","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":"Low-temperature plasma effect-induced enhancement of osteogenic activity in calcium phosphate ceramics","authors":"Fengxiong Luo ,&nbsp;Yu Yang ,&nbsp;Dongxuan Li ,&nbsp;Ruiqi Mao ,&nbsp;Yawen Huang ,&nbsp;Jian Lu ,&nbsp;Xiangdong Zhu ,&nbsp;Kefeng Wang ,&nbsp;Yujiang Fan ,&nbsp;Xingdong Zhang","doi":"10.1016/j.actbio.2025.04.048","DOIUrl":"10.1016/j.actbio.2025.04.048","url":null,"abstract":"<div><div>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.</div></div><div><h3>Statement of Significance</h3><div>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.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 667-685"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044690","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":"Effects of iron accumulation and its chelation on oxidative stress in intracortical implants","authors":"Melissa E. Franklin ,&nbsp;Jordan L. Grant ,&nbsp;Grant M. Lee ,&nbsp;Anabel Alvarez-Ciara ,&nbsp;Cassie Bennett ,&nbsp;Serene Mattis ,&nbsp;Nicolas Gallardo ,&nbsp;Natalie Corrales ,&nbsp;Xinyan Tracy Cui ,&nbsp;Jeffrey R. Capadona ,&nbsp;Wolfgang J. Streit ,&nbsp;Jean-Hubert Olivier ,&nbsp;Robert W. Keane ,&nbsp;W. Dalton Dietrich ,&nbsp;Juan Pablo de Rivero Vaccari ,&nbsp;Abhishek Prasad","doi":"10.1016/j.actbio.2025.05.026","DOIUrl":"10.1016/j.actbio.2025.05.026","url":null,"abstract":"<div><div>Long-term reliability of microelectrodes implanted in the cortex is hindered due to the foreign body response that occurs at the electrode-tissue interface. Following implantation, there is disruption of the blood-brain-barrier and vasculature, resulting in activation of immune cells and release of erythrocytes. As a result of hemolysis, erythrocytes degrade to heme and then to free iron. Excess free iron can participate in the Fenton Reaction, producing reactive oxygen species (ROS). Iron-mediated ROS production can contribute to oxidation of lipids, proteins, and DNA, facilitating a hostile environment of oxidative stress leading to oxidative cellular damage, cytotoxicity, and cell death. The objective of this study was to show the iron accumulation and the downstream effects of oxidative stress at the injury site. A 16-channel microelectrode array (MEA) was implanted in the rat somatosensory cortex. Our results indicated significant elevation of NOX complex subunits across timepoints, suggesting sustained oxidative stress. In a separate group of animals, we administered an iron chelator, deferoxamine mesylate (DFX), to evaluate the effects of chelation on iron accumulation, oxidative stress and damage, and neuronal survival. Results indicate that animals with iron chelation showed reduced ferric iron and markers of oxidative stress and damage corresponding with increased expression of neuronal cell bodies and electrophysiological functional performance. In summary, the study reveals the role of iron in mediating oxidative stress and the effects of modulating iron levels using iron chelation at the electrode-tissue interface.</div></div><div><h3>Statement of significance</h3><div>Iron accumulation has been observed in central nervous system injuries and in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. While the role of iron is studied in various neurodegenerative diseases and traumatic brain injury, iron accumulation and its effect on oxidative stress is not known for intracortical implants where there is a persistent injury due to the presence of a foreign device in the brain tissue. The study seeks to understand the effects of iron accumulation on oxidative stress and damage at the electrode-tissue interface in intracortical implants by using iron chelation as a method of modulating iron levels at the interface.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 703-723"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047859","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-Formed Tissue-Adhesive Macroporous Scaffolds Enhance Cell Infiltration and Tissue Regeneration","authors":"Farnoosh Saeedinejad ,&nbsp;Fatemeh Alipanah ,&nbsp;Steven Toro ,&nbsp;Noah Pereira ,&nbsp;Delaram Ghanbariamin ,&nbsp;Ivan Jozic ,&nbsp;Tannin A. Schmidt ,&nbsp;Elmira Arab-Tehrany ,&nbsp;Yu Shrike Zhang ,&nbsp;Ali Tamayol ,&nbsp;Mohamadmahdi Samandari","doi":"10.1016/j.actbio.2025.04.049","DOIUrl":"10.1016/j.actbio.2025.04.049","url":null,"abstract":"<div><div>Macroporous hydrogels have shown significant promise in tissue engineering and regenerative medicine. However, conventional macroporous scaffold fabrications are complex and incompatible with <em>in situ</em> customization and fabrication. Here, we propose a highly translational approach for the <em>in situ</em> formation of adhesive macroporous scaffolds through microfluidic homogenization of gas into a self-crosslinkable gelatin and transglutaminase (TG) mixture using a double syringe system. Using this strategy, the tissue defect can be evaluated, and the precursor, with the desired composition and volume, foamed and administered <em>in situ</em>. The TG-induced crosslinking stabilizes the pores, leading to strong tissue adhesion and accurate defect geometry approximation. We demonstrate precise control over the porosity, by changing the foaming parameters, and crosslinking kinetics, by adjusting the concentration of gelatin and TG. The resulting foam scaffolds offer controlled pore distribution, flexibility, tissue adhesion, stability, sustained protein release profile, and cell permissibility, with a faster biodegradation profile compared to bulk hydrogel compartments. Consequently, enhanced cell infiltration and reduced fibrous capsule formation are observed upon subcutaneous injection of foams compared to bulk hydrogels. Finally, the scaffolds demonstrate significant improvements in the rate and quality of the healing compared to the bulk hydrogels for the treatment of full-thickness cutaneous wounds in mice.</div></div><div><h3>Statement of Significance</h3><div>A highly translational method is presented for the <em>in situ</em> formation of tissue-adhesive macroporous scaffolds through microfluidic homogenization of gas into a self-crosslinkable hydrogel precursor using a double syringe system. This approach allows precise control over porosity and pore size, facilitating cell infiltration, tissue integration, and improved wound healing compared to bulk hydrogels, highlighting their potential in regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 358-377"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059462","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":"Enhanced delivery of camptothecin to colorectal carcinoma using a tumor-penetrating peptide targeting p32","authors":"Yanhao Jiang ,&nbsp;Zhiren Wang ,&nbsp;Wenpan Li ,&nbsp;Teng Ma ,&nbsp;Mengwen Li ,&nbsp;Shuang Wu ,&nbsp;Ethan Lin ,&nbsp;Karlie Elizabeth Flader ,&nbsp;Mengjiao Ma ,&nbsp;Mengyang Chang ,&nbsp;Hongmin Li ,&nbsp;Wei Wang ,&nbsp;Jianqin Lu","doi":"10.1016/j.actbio.2025.05.036","DOIUrl":"10.1016/j.actbio.2025.05.036","url":null,"abstract":"<div><div>Camptothesome, a sphingomyelin (SM)-conjugated camptothecin (CPT) vesicular nanotherapeutic, addresses the poor solubility and lactone instability of CPT while enhancing drug loading, pharmacokinetics, and tumor distribution compared to CPT physically entrapped in conventional liposomes. Despite these improvements, the tumor uptake remains limited. To further enhance the tumor delivery efficiency and minimize the off-target distribution, we functionalize Camptothesome with the LinTT1 peptide, a CendR motif, which binds to overexpressed p32 proteins on tumor cell surface, initiating effective transcytosis for deep tumor penetration. Via systematic screening, the optimal peptide ratio on Camptothesome is identified. LinTT1/Camptothesome significantly increases cancer cell uptake without affecting normal cell internalization, resulting in enhanced anti-colorectal cancer cells activity. Additionally, decorating Camptothesome with the LinTT1 cell-penetrating peptide enables effective transcytosis via a Golgi-dependent intracellular trafficking mechanism, significantly improving the intratumoral delivery while reducing distribution to normal tissues. In a human HCT116 xenograft colorectal cancer (CRC) mouse model, LinTT1/Camptothesome demonstrates superior antitumor efficacy compared to both Camptothesome and Onivyde by upregulating cleaved caspase-3 and γH2AX. Our study substantiates the potential of leveraging a tumor-penetrating peptide to enhance the tumor delivery efficiency of Camptothesome, maximizing its therapeutic index for improved treatment of human CRC.</div></div><div><h3>Statement of significance</h3><div>Despite the improved tumor delivery achieved by Camptothesome, its tumor distribution and penetration remain limited. This is because the enhanced permeability and retention effect only facilitates nanotherapeutic distribution to tumor periphery through leaky vasculature. The C-end Rule (CendR) motif-neuropilin receptor system enhances tumor-homing peptides by binding to cellular surface receptors, triggering transcytosis. Herein, LinTT1, the most potent CendR peptide that binds to the overexpressed p32 receptor on cancer cells, was effectively engineered onto Camptothesome using thiol-maleimide lipid chemistry. The LinTT1/Camptothesome significantly enhanced tumor uptake and penetration while minimizing accumulation in normal tissues, demonstrating remarkable anticancer efficacy in a human xenograft colorectal cancer model. Our findings highlight the critical role of tumor-homing peptides in unlocking the full therapeutic potential of Camptothesome.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 629-640"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086049","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":"Sex- and region-specific differences in microstructural remodeling and passive biomechanics of the aorta correlate with aneurysm propensity in a mouse model of severe Marfan syndrome","authors":"Krashn Kumar Dwivedi,&nbsp;Yufan Wu,&nbsp;Jacob Rother,&nbsp;Jessica E. Wagenseil","doi":"10.1016/j.actbio.2025.05.056","DOIUrl":"10.1016/j.actbio.2025.05.056","url":null,"abstract":"<div><div>Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the gene that encodes fibrillin-1, a glycoprotein necessary for elastic fiber assembly and stability in the large elastic arteries. MFS is associated with aortic aneurysms that typically occur in the proximal ascending aorta and have worse outcomes in males. Mechanisms for the sex- and region-specific differences in aneurysm development and outcomes are unknown. We quantified aortic geometry, microstructural remodeling, and passive biomechanics of the thoracic ascending, thoracic descending, abdominal suprarenal, and abdominal infrarenal aorta in 4 months old male and female <em>Fbn1^mgR/mgR</em> (a model of severe MFS) and littermate wild-type mice to determine correlations between aortic geometry, microstructural remodeling, biomechanics, and aneurysmal dilation. We showed that aneurysmal dilation was strongly correlated with unloaded thickness, microstructural remodeling including loss of elastic fibers, deposition of collagen fibers, and decrease in cell nuclei number, and mechanical metrics including physiologic and ex vivo circumferential material stiffness. A multivariable mixed model showed that unloaded thickness, elastic fiber degradation, and ex vivo material stiffness predicted aneurysmal dilation with an adjusted R² = 0.8818. Our results highlight the potential of geometric, microstructural remodeling, and biomechanical metrics to serve as physical biomarkers for personalized aortic aneurysm diagnosis and management in MFS.</div></div><div><h3>Statement of significance</h3><div>Marfan syndrome (MFS) is a genetic disease associated with aortic aneurysms that have distinct sex- and region-specific outcomes. The mechanisms driving these variations are unclear. We used a severe MFS mouse model (<em>Fbn1^mgR/mgR</em>) to explore differences in microstructural remodeling and passive wall mechanics along the aortic length in males and females. We correlated these changes with aneurysm severity, as quantified by aortic dilation. We found that sex- and region-specific alterations in unloaded thickness, microstructural remodeling, and passive mechanical properties of the aortic wall play a critical role in aortic dilation. Our findings showed that mechanical metrics, particularly ex vivo material stiffness, may serve as biomarkers for the diagnosis and management of aortic aneurysms.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 218-235"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144919","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":"Trimethylamine N-oxide–derived zwitterion coating for polyurethane ureteral stents prevents encrustation formation","authors":"Kaiguo Xia ,&nbsp;Guang Chen ,&nbsp;Bingbing Hou ,&nbsp;Zhe Wang ,&nbsp;Yaqi Zhu ,&nbsp;Yuexian Xu ,&nbsp;Shanfu Zhang ,&nbsp;Qiang Xuan ,&nbsp;Yezi You ,&nbsp;Zongyao Hao","doi":"10.1016/j.actbio.2025.04.058","DOIUrl":"10.1016/j.actbio.2025.04.058","url":null,"abstract":"<div><div>A ureteral stent with strong resistance to proteins, bacteria, and multivalent ions is crucial for the safe treatment of urologic diseases. Generally, the proteins, bacteria, and multivalent ions present in urine tend to bind to the stent surface, leading to aggregation, nucleation, and subsequent stent encrustation. Stent encrustation can induce or exacerbate urinary tract infections and obstructions, thereby seriously harming kidney function. Although hydrophilic coatings on ureteral stents can reduce the binding of proteins, bacteria, and multivalent ions, encrustation still occurs. To date, preventing stent encrustation formation remains a significant challenge. Here, we grafted dense trimethylamine oxide (TMAO)-derived zwitterionic polymers onto the stent surface via a branched amplification strategy. These zwitterions can strongly bind water molecules, forming a stable hydration layer that repels proteins, bacteria, and multivalent ions from adhering to the surface of the polyurethane ureteral stent, thus rendering the stent anti-encrustation. The results showed that the TMAO-derived zwitterion-coated stents exhibited a significantly reduced encrustation weight (13.8% of the original polyurethane stent) and demonstrated good safety. This approach offers a promising method for enhancing stent encrustation resistance.</div></div><div><h3>Statement of Significance</h3><div>This study successfully developed a TMAO-derived zwitterionic coating on the surface of a polyurethane stent, creating a superhydrophilic surface with a minimal contact angle of 5.2^o. This surface effectively shields the stent from interactions with proteins, bacteria, and multivalent ions in urine, demonstrating favorable anti-protein adsorption and antibacterial adhesion properties. The superhydrophilic surface formed by the TMAO-derived zwitterionic coating on the stents (PTMAO-s) provides strong anti-fouling resistance and enhanced anti-encrustation properties. Under identical conditions, the encrustation resistance of PTMAO-s is approximately 7.2-fold greater than that of original polyurethane stents (PU), 3.6-fold greater than Bard commercial stents, and 2.1-fold greater than betaine-coated stents (PSBG-s).</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 464-475"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994093","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":"Effects of PDMS culture on stem cell differentiation towards definitive endoderm and hepatocytes","authors":"Christopher T. Clark ,&nbsp;Yao Wang ,&nbsp;Devin C. Johnson ,&nbsp;Seohyun C. Lee ,&nbsp;Quinton Smith","doi":"10.1016/j.actbio.2025.05.017","DOIUrl":"10.1016/j.actbio.2025.05.017","url":null,"abstract":"<div><div>The generation of human induced pluripotent stem cell (hiPSC) derivatives for regenerative medicine applications holds tremendous promise in treating various disorders. One critical target includes liver disease, in which the primary curative treatment is a cellular transplant aimed to restore the lost function of hepatocytes. In an effort to improve the differentiation of hiPSC-derived liver tissue, we manipulated the mechanical conditions of endoderm specification through directed perturbation of the cytoskeleton and through 2D substrate culture on viscoelastic materials. Through a combination of qRT-PCR, immunofluorescence staining, and functional assays, we found that mechanical cues can bias endoderm specification in an actomyosin and Yes-associated protein (YAP) dependent manner, unveiling new insights into mechanotransduction in germ layer specification and downstream maturation toward parenchymal cells.</div></div><div><h3>Statement of significance</h3><div>The translational potential of using human induced pluripotent stem cell (hiPSC) derived hepatocytes to therapeutically improve impaired liver function holds great clinical promise. However, challenges remain in efficiently differentiating functional hepatocytes with mature marker expression. In an effort to improve the differentiation efficiency of hepatocytes, the role of early mechanosensing mechanisms was investigated in the specification of hiPSCs to definitive endoderm progenitor populations. Through a combination of cytoskeletal modulation, control of mechanoresponsive, yes-associated protein expression, and culture on physiologically compliant PDMS substrates, we found that soft environments not only improve progenitor specification but also impact the downstream functionality of differentiated hepatocytes. These results contribute to the collective appreciation that mechanical cues are critical in developmental processes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 508-519"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055713","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":"Emergence of snail mucus as a multifunctional biogenic material for biomedical applications","authors":"Pritha Sarkar ,&nbsp;Disha Iyengar ,&nbsp;Kausik Mukhopadhyay","doi":"10.1016/j.actbio.2025.05.006","DOIUrl":"10.1016/j.actbio.2025.05.006","url":null,"abstract":"<div><div>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.</div></div><div><h3>Statement of Significance</h3><div>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.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 21-46"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045845","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":"A Chitosan-based Hydrogel to Modulate Immune Cells and Promote Periodontitis Healing in the High-Fat Diet-induced Periodontitis Rat Model","authors":"Yi Zhu ,&nbsp;Aiman Ali ,&nbsp;Gabriel Mulinari dos Santos ,&nbsp;João Paulo Soares Franciscon ,&nbsp;Rafael Scaf de Molon ,&nbsp;Cynthia Goh ,&nbsp;Edilson Ervolino ,&nbsp;Leticia Helena Theodoro ,&nbsp;Annie Shrestha","doi":"10.1016/j.actbio.2025.05.034","DOIUrl":"10.1016/j.actbio.2025.05.034","url":null,"abstract":"<div><div>Periodontitis is a multifactorial inflammatory disease driven by prolonged, dysregulated inflammation between dysbiotic microbiota and the host immune system. Risk factors such as metabolic syndrome exacerbate periodontitis progression through systemic inflammation. Current treatments primarily focus on removing pathogenic dental plaque, but subsequent healing relies mainly on the host immune response. Modulating the local immune environment, particularly dendritic cells (DCs) and T-cells, in periodontitis complicated by metabolic syndrome could enhance the healing process. The objective of this study is to develop a biomaterial-based adjuvant therapy to immunomodulate DCs and T-cells and promote healing in periodontitis complicated by metabolic syndrome. We developed and characterized a chitosan-based thermosensitive injectable self-assembled hydrogel (TISH), which exhibited an interconnected porous structure conducive to cell migration and adhesion. TISH was loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) and resveratrol (TISH(GR)), enabling sustained release over time. Mechanistically, TISH(GR) suppressed inflammatory signalling pathways (MAPKs and NF-κB) downstream of Toll-like receptor-4 in DCs. In a high-fat diet-induced periodontitis rat model, TISH(GR) administered as an adjuvant to SRP significantly alleviated periodontal inflammation and tissue destruction compared to SRP alone. TISH(GR) treatment was associated with decreased TH17 cell infiltration and elevated expression of the Tregs-associated cytokine IL-10 in the periodontium. In conclusion, TISH(GR) was developed and optimized as an injectable immunomodulatory hydrogel targeting DCs and T-cells. It demonstrated promising potential to attenuate inflammation and enhance periodontal healing, particularly in immunocompromised patients with metabolic syndrome.</div></div><div><h3>Statement of significance</h3><div>Current treatments for periodontitis primarily focus on dental plaque removal, with healing heavily dependent on the host immune system. However, metabolic diseases can dysregulate the local immune response, exacerbating periodontal inflammation and impairing post-treatment healing. In this study, we developed a chitosan-based hydrogel designed to immunomodulate dendritic cells and T-cells, polarizing them toward an anti-inflammatory phenotype that promotes tissue repair. When administered as an adjuvant to scaling and root planing, this combination therapy significantly enhanced periodontal healing and reduced tissue damage in a high-fat diet complicated periodontitis model. These findings highlight the clinical potential of this hydrogel formulation to improve treatment outcomes, particularly in challenging clinical cases involving metabolic comorbidities.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 452-463"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087089","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}