Acta Biomaterialia最新文献

{"title":"The ultrastructure of the starfish skeleton is correlated with mechanical stress","authors":"Raman,&nbsp;Susanna Labisch,&nbsp;Jan-Henning Dirks","doi":"10.1016/j.actbio.2024.12.032","DOIUrl":"10.1016/j.actbio.2024.12.032","url":null,"abstract":"<div><div>Echinoderms and vertebrates both possess mesodermal endoskeletons. In vertebrates, the response to mechanical loads and the capacity to remodel the ultrastructure of the skeletal system are fundamental attributes of their endoskeleton. To determine whether these characteristics are also inherent in Echinoderms, we conducted a comprehensive biomechanical and morphological study on the endoskeleton of <em>Asterias rubens</em>, a representative model organism for Echinoderm skeletons. Our analysis involved high-resolution X-ray CT scans of entire individual ossicles, covering the full stereom distribution along with the attached muscles. Leveraging this data, we conducted finite element analysis to explore the correlation between mechanical loads acting on an ossicle and its corresponding stereom structure. To understand the effects of localized stress concentration, we examined stereom regions subjected to high mechanical stress and compared them to areas with lower mechanical stress. Our results show that the stereom microstructure, both in terms of thickness and orientation, corresponds closely to the mechanical loading experienced by the ossicles. Additionally, by comparing the stereom structures of ossicles in various developmental stages, we assessed the general remodeling capacity of these ossicles. Our findings suggest that the ability to adapt to mechanical loads is a common feature of mesoderm endoskeletons within the Deuterostomia taxonomic group. However, the material remodelling may be a specific trait unique to vertebrate endoskeletons.</div></div><div><h3>Statement of Significance</h3><div>This study shows a correlation between the ultrastructure and the mechanical stress in the starfish endoskeleton, suggesting that this fundamental structure-function relationship may be an ancestral feature of not only vertebrate endoskeletons. However, unlike vertebrate skeletons, not all starfish ossicles remodel in response to changing stress, indicating a potential divergence in skeletal adaptation mechanisms. Our methodological approach combines morphometrics and finite element modeling and thus provides a powerful tool to investigate biomechanics in complex skeletal structures.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 279-290"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the mechanics of networked type II collagen: Experiments, constitutive modeling, and validation","authors":"Phoebe Szarek ,&nbsp;David M. Pierce","doi":"10.1016/j.actbio.2024.12.043","DOIUrl":"10.1016/j.actbio.2024.12.043","url":null,"abstract":"<div><div>In this study we investigate the mechanics of type II collagen fibrils, an essential structural component in many load-bearing tissues including cartilage. Although type II collagen plays a crucial role in maintaining tissue integrity, the stress–stretch and failure response of type II collagen fibrils in tension is not established in the current mechanics literature. To address this knowledge gap, we conducted tensile tests on isolated collagen networks from articular cartilage and established a validated constitutive model for type II collagen fibril. We identified two distinct failure mechanisms: one without softening before failure and another with pronounced softening. Our findings reveal that network morphology significantly influences the bulk mechanical response, providing a framework for modeling the complex behavior of collagen fibrils in both healthy and diseased tissues. The validated model enhances the accuracy of finite element models used in analyses of soft tissues and may deepen our understanding of the mechanical progression of diseases like osteoarthritis. Our results offer valuable insights into the mechanics of type II collagen, with implications for improving computational models and for guiding future studies in tissue regeneration and disease treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 267-278"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960191","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 bacteria-responsive nanoplatform with biofilm dispersion and ROS scavenging for the healing of infected diabetic wounds","authors":"Yin Zheng ,&nbsp;Mingyue Wang ,&nbsp;Xinge Zhang ,&nbsp;Zhongming Wu ,&nbsp;Ling Gao","doi":"10.1016/j.actbio.2024.12.042","DOIUrl":"10.1016/j.actbio.2024.12.042","url":null,"abstract":"<div><div>Delayed wound healing in patients with diabetes remains a major health challenge worldwide. Uncontrolled bacterial infection leads to excessive production of reactive oxygen species (ROS) and persistent inflammatory responses, which seriously hinder conventional physiological healing processes after injury. Biofilms, as protective barriers for bacteria, pose a critical obstacle to effective bacterial eradication. Herein, an innovative therapeutic nanoplatform with <em>in situ</em> antibacterial and antioxidant properties is developed for enhancing infected diabetic wound healing. The enrichment of phenylboronic acid (PBA) moieties on the nanoplatform enhances biofilm penetration, actively anchors and aggregates the enclosed bacteria through the \"multivalent effect\", with an anchoring efficiency as high as 80 %. Additionally, glycine moieties on the nanoplatform ensure spatial extensibility by charge repulsion, enabling targeted antibiotic release around bacteria. This precise antibacterial effect increases the bactericidal activities of the nanoplatform against <em>S. aureus</em> or <em>P. aeruginosa</em> by 25 % and 22 % respectively, effectively eliminating the bacteria and dispersing the biofilms. Furthermore, 3,4-dihydropyrimidin-2(1H)-one (DHPM) moieties act as ROS scavengers that alleviate oxidative stress and inflammatory responses, promoting tissue repair progression into the proliferative phase characterized by increased extracellular matrix deposition, angiogenesis, and granulation tissue formation, ultimately accelerating diabetic wound healing. Overall, this work presents an innovative bacterial response strategy for achieving <em>in situ</em> antibacterial and antioxidant effects in infected tissues and provides a promising therapeutic approach for treating infected diabetic wounds.</div></div><div><h3>Statement of significance</h3><div>Infected diabetic wound management remains a major world health issue. Severe bacterial infection leads to excessive oxidative stress and persistent inflammatory response, which seriously hinders the wound healing process. As a protective barrier for bacteria, biofilms are a key obstacle to effective bacterial clearance. This study provides a bacteria-responsive nanoplatform for the healing of infected diabetic wounds. The nanoplatform not only exhibits improved biofilm penetration but also actively anchors the enclosed bacteria and enables targeted antibiotic release to disperse the biofilm. The DHPM moieties of the nanoplatform act as ROS scavengers which could alleviate inflammatory responses, promote tissue repair progression into the proliferative phase, and ultimately accelerate diabetic wound repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 545-558"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878926","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 GSH-responsive oxidative stress nanoamplifier for self-augmented chemo/chemodynamic therapy to reverse cisplatin resistance","authors":"Yanjuan Huang ,&nbsp;Meng Xia ,&nbsp;Congjun Xu ,&nbsp;Zijun Lin ,&nbsp;Meixu Chen ,&nbsp;Xianmin Shi ,&nbsp;Yaqing Ding ,&nbsp;Yan Xiao ,&nbsp;Chunshun Zhao","doi":"10.1016/j.actbio.2024.12.041","DOIUrl":"10.1016/j.actbio.2024.12.041","url":null,"abstract":"<div><div>Drug resistance and off-target toxicity of cisplatin (CDDP) pose significant challenges in effectively treating non-small cell lung cancer (NSCLC). Recently, chemodynamic therapy (CDT), an emerging reactive oxygen species (ROS)-mediated tumor-specific therapeutic modality, has shown great potential in sensitizing multidrug resistance tumor cells. Herein, a glutathione (GSH)-responsive Pt(IV) prodrug-based oxidative stress nanoamplifier (CuBSO@Pt_C16) was developed for effective chemo/chemodynamic therapy to reverse CDDP resistance in NSCLC. CuBSO@Pt_C16, a lipid-coated nanoagent, was constructed by coordinating Cu²⁺ with l-buthioninesulfoximine (BSO) as the core framework, and Pt(IV) prodrug (Pt_C16) was concurrently loaded on the outer lipid bilayer. With appropriate particle size (∼35 nm) and good physiological stability, CuBSO@Pt_C16 efficiently accumulated at tumor tissue. Under high intracellular GSH levels, Pt_C16 was reduced to generate cytotoxic CDDP that induced cell-killing and boosted intracellular H₂O₂ levels, and the CuBSO core was disassembled to release Cu ions and BSO simultaneously. The released BSO could efficiently reduce the intracellular GSH content to weaken its detoxification effect on CDDP, leading to more Pt-DNA adduct formation and more severe DNA damage. Meanwhile, Cu ions catalyzed the intracellular elevated H₂O₂ into highly lethal •OH through Fenton-like reactions, and the reduction of GSH weakened the •OH elimination, which jointly amplified the intracellular oxidative stress levels, finally achieving enhanced chemo/chemodynamic therapeutic effect and reversing CDDP resistance in NSCLC. Therefore, this work offers an inspirational idea for effectively treating drug-resistant cancers.</div></div><div><h3>Statement of significance</h3><div>Cisplatin (CDDP) faces challenges in treating non-small cell lung cancer (NSCLC) due to drug resistance and off-target toxicity. Herein, a GSH-responsive nanoreactor (CuBSO@Pt_C16) was developed for effective chemo/chemodynamic therapy to address CDDP resistance. CuBSO@Pt_C16 could efficiently traffic to tumor site and response to high GSH levels in tumor cells to release CDDP, Cu ions and buthioninesulfoximine (BSO) simultaneously. CDDP could induce DNA damage and boost intracellular H₂O₂ levels, which then served as the substrate of Cu to induce •OH generation through Fenton-like reactions. Meanwhile, the released BSO efficiently reduced the intracellular GSH content to weaken its detoxification effect on CDDP and the elimination of the •OH, leading to amplified intracellular oxidative stress and more severe damage to induce cell death.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 440-454"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873573","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 self-forming bone membrane generated by periosteum-derived stem cell spheroids enhances the repair of bone defects","authors":"Jintao Zhong ,&nbsp;Wenhua Li ,&nbsp;Hetong Li ,&nbsp;Jin Zhang ,&nbsp;Zuoxu Hou ,&nbsp;Xiao Wang ,&nbsp;Enhui Zhou ,&nbsp;Ke Lu ,&nbsp;Weida Zhuang ,&nbsp;Hongxun Sang","doi":"10.1016/j.actbio.2024.12.058","DOIUrl":"10.1016/j.actbio.2024.12.058","url":null,"abstract":"<div><div>The periosteum, a highly specialized thin tissue, is instrumental in contributing to as much as 70 % of early bone formation. Recognizing the periosteum's vital physiological roles, the fabrication of a biomimetic periosteum has risen as an auspicious strategy for addressing extensive bone defects. In the study, we obtained such biomimetic periosteum by utilizing periosteum-derived stem cells (PDSCs) spheroids. These spheroids are induced to spontaneously generate a bioactive membrane on a delicate 3D-printed polycaprolactone (PCL) substrate. This process yields a biomimetic periosteum rich in the resources needed for bone repair. The <em>in vitro</em> evaluations demonstrated that this membrane can act as a repository for growth factors and stem cells. The release kinetics confirmed a sustained delivery of BMP-2 and VEGF, which promoted enhanced osteogenesis and angiogenesis <em>in vitro</em>, respectively. The <em>in vivo</em> results further highlighted robust bone regeneration from critical cranial defects upon the application of this biomimetic periosteum. The biomimetic periosteum, easily harvested and potent in bioactivity, presents substantial clinical potential, particularly for the treatment of critical-sized bone defects.</div></div><div><h3>Statement of Significance</h3><div>PDSC theoretically demonstrates substantial potential in membrane construction, a value we've harnessed in this pioneering application. By employing cell spheroids, we've successfully integrated a substantial number of cells into the membrane framework. PDSC spheroids exhibit the remarkable ability to self-assemble into functional membranes, endowing them with robust biological capabilities that enhance their performance in biological systems. The <em>in vitro</em> evaluations demonstrated that this membrane can act as a repository for growth factors and stem cells. The <em>in vivo</em> bone repair facilitated by this membrane is notably effective, characterized by superior bone quality and accelerated formation rates. This process mirrors the natural intramembrane ossification, offering a promising approach to bone integration and regeneration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 185-201"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916474","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":"Long-range directional growth of neurites induced by magnetic forces","authors":"Tasmin Nahar ,&nbsp;Monte Gates ,&nbsp;Emilie Secret ,&nbsp;Jean-Michel Siaugue ,&nbsp;Jérôme Fresnais ,&nbsp;Michael Rotherham ,&nbsp;Heidi R. Fuller ,&nbsp;Sharon J. Brown ,&nbsp;Alicia J. El Haj ,&nbsp;Neil D. Telling","doi":"10.1016/j.actbio.2024.12.057","DOIUrl":"10.1016/j.actbio.2024.12.057","url":null,"abstract":"<div><div>The ability to control the growth and orientation of neurites over long distances has significant implications for regenerative therapies and the development of physiologically relevant brain tissue models. In this study, the forces generated on magnetic nanoparticles internalised within intracellular endosomes are used to direct the orientation of neuronal outgrowth in cell cultures. Following differentiation, neurite orientation was observed after 3 days application of magnetic forces to human neuroblastoma (SH-SY5Y) cells, and after 4 days application to rat cortical primary neurons. The direction of neurite outgrowth was quantified using a 2D Fourier transform analysis, showing agreement with the derived magnetic force vectors. Orientation control was found to be effective over areas &gt;1cm² using modest forces of ∼10 fN per endosome, apparently limited only by the local confluence of the cells. A bioinformatics analysis of protein expression in cells exposed to magnetic forces revealed changes to cell signaling and metabolic pathways resulting in enhanced carbohydrate metabolism, as well as the perturbation of processes related to cellular organisation and proliferation. Additionally, in cell culture regions where the measured force vectors converged, large (∼100 µm) SH-SY5Y neuroclusters loaded with nanoparticles were found, connected by unusually thick linear neurite fibres. This could suggest a magnetically driven enhancement of neurocluster growth, with the clusters themselves contributing to the local forces that direct outgrowth. Such structures, which have not been previously observed, could provide new insights into the development and possible enhancement of neural circuitry.</div></div><div><h3>Statement of Significance</h3><div>A magnetic force approach for directing outgrowth in neuronal cells over macroscopic areas is successfully demonstrated. Cells were incubated with magnetic nanoparticles which were sequestered into intracellular compartments. Permanent magnet arrays created local intracellular magnetic force vectors mediated via the internalized nanoparticles, which were found to precisely guide neurite orientation. Analysis of cellular protein expression suggested the mechanism for directed growth involved specific cell signaling and metabolic pathways. In addition, highly unusual straight and thick neural fibers were observed that connected large ‘magnetic’ spherical cell clusters. The results reported will advance nanotechnology and cell therapy for neuro-regeneration where magnetic forces could help to reconnect damaged neurons, or even build artificial neuronal architectures.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 215-230"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printed biomimetic bilayer limbal implants for regeneration of the corneal structure in limbal stem cell deficiency","authors":"Leying Wang ,&nbsp;Xiongfeng Nie ,&nbsp;Yuan Wei ,&nbsp;Qiankun Chen ,&nbsp;Yage Sun ,&nbsp;Xinrui Zhao ,&nbsp;Xizhan Xu ,&nbsp;Wenguang Liu ,&nbsp;Qingfeng Liang","doi":"10.1016/j.actbio.2025.01.011","DOIUrl":"10.1016/j.actbio.2025.01.011","url":null,"abstract":"<div><div>Limbal stem cell deficiency (LSCD) causes vision loss and is often treated by simple corneal epithelial cell transplantation with poor long-term efficiency. Here, we present a biomimetic bilayer limbal implant using digital light processing 3D printing technology with gelatin methacrylate (GelMA) and poly (ethylene glycol) diacrylate (PEGDA) bioinks containing corneal epithelial cells (CECs) and corneal stromal stem cells (CSSCs), which can transplant CECs and improve the limbal niche simultaneously. The GelMA/PEGDA hydrogel possessed robust mechanical properties to support surgical transplantation and had good transparency, suitable swelling and degradation rate as a corneal implant. Encapsulated CECs and CSSCs maintained viability and proliferative activity in the bilayer limbal implant. In vivo, both CEC-loaded and CEC/CSSC-loaded hydrogel could repair the corneal surface in the LSCD model effectively. Notably, the corneal epithelial healing was faster, and corneal opacity and neovascularization were minimal in CEC/CSSC-loaded group. These findings highlight the feasibility of 3D printing in limbal construction, providing CEC/CSSC-loaded limbal implants as a treatment strategy for LSCD and corneal blindness.</div></div><div><h3>Statement of significance</h3><div>This study aimed to enhance the long-term prognosis of limbal epithelial cell transplantation in patients with limbal stem cell deficiency by developing a 3D limbal implant that encapsulates corneal epithelial cells and limbal niche cells simultaneously. The 3D printed implant offers the advantages of mimicking the natural layered limbal structure and were found to enhance the regenerative capacity of corneal epithelial cells, suppress inflammation, and alleviate corneal scarring in vivo. This study highlights the importance of limbal microenvironment remodeling in the treatment of limbal stem cell deficiency and the potential of 3D printing in the treatment of corneal diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 157-170"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973562","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 of hemoglobin microbubbles for acoustic blood oxygen sensing: A study on PEGylation and gas core modification for in vivo applications","authors":"Ghazal Rastegar ,&nbsp;Bahareh Kianpour ,&nbsp;Teja Pathour,&nbsp;Mohammad Musa Salman,&nbsp;Shashank R. Sirsi","doi":"10.1016/j.actbio.2024.12.024","DOIUrl":"10.1016/j.actbio.2024.12.024","url":null,"abstract":"<div><div>The creation of innovative ultrasound contrast agents (UCAs) with the ability to monitor oxygen levels in real-time holds immense potential for advancing early diagnosis of various medical conditions such as hypoxic/reperfusion injury. In this study, we propose the development of oxygen sensitive UCAs using microbubbles composed of hemoglobin (HbMBs), which can function as sensors for blood oxygen levels. Previously, we performed a study highlighting the initial proof-of-concept efficacy of air-filled HbMBs in detecting oxygenation changes in vitro, offering a promising tool for clinically detecting tissue hypoxia. Nevertheless, a significant drawback of this approach is the potential for immune reactions and toxicity when hemoglobin is outside its natural red blood cell environment. Moreover, in vitro, HbMBs had low stability, with more than 90% decrease in their concentration after 120 minutes. Therefore, careful consideration of the surface properties and the gas core of HbMBs is crucial. Here, we formulated PEGylated HbMBs (PHbMBs), and investigated their stability, immunogenicity, and their acoustic response in oxygenated and deoxygenated media in vitro. We optimized PEGylated HbMBs (PHbMBs), showing a 42% reduction in immunogenicity and significantly improved stability in vitro, while maintaining their oxygen-binding and acoustic response. In vivo, PHbMBs demonstrated similar contrast enhancement to that of non-PEGylated MBs, demonstrating that PEGylation does not decrease HbMBs’ acoustic signaling. Finally, changing the gas core from air to PFB increased PHbMBs’ mean circulation time more than 11-fold, without diminishing their responsiveness to oxygen. Overall, the proposed oxygen sensitive PHbMBs offer a promising avenue for real-time acoustic detection of blood oxygen levels, paving the way for potential clinical applications in monitoring critically ill patients.</div></div><div><h3>Statement of significance</h3><div>This research explores the emergent field of Acoustic Oxygen Imaging in vivo using hemoglobin-based microbubbles. This innovative contrast agent approach involves imaging using crosslinked biomaterial comprised of the hemoglobin protein, aiming to transform the way we monitor blood oxygen levels with ultrasound.</div><div>This work fundamentally addresses central concerns of improving bubble stability and circulation life for eventual clinical use, while minimizing toxicity. Importantly, we demonstrate that PEGylation of hemoglobin microbubbles enhances their stability, reduces immunogenicity, and maintains acoustic responsiveness. The incorporation of perfluorobutane into the bubble core increases the longevity of these microbubbles in circulation, while sustaining their oxygen sensitivity. Favorable in vivo results highlight the potential of this technology in real-time acoustic detection of blood oxygen levels.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 305-315"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822865","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 of a peptide-based tumor-activated checkpoint inhibitor for cancer immunotherapy","authors":"Zhen Zhao,&nbsp;John Fetse,&nbsp;Umar-Farouk Mamani,&nbsp;Yuhan Guo,&nbsp;Yuanke Li,&nbsp;Pratikkumar Patel,&nbsp;Yanli Liu,&nbsp;Chien-Yu Lin,&nbsp;Yongren Li,&nbsp;Bahaa Mustafa,&nbsp;Kun Cheng","doi":"10.1016/j.actbio.2024.12.051","DOIUrl":"10.1016/j.actbio.2024.12.051","url":null,"abstract":"<div><div>Antibody-based checkpoint inhibitors have achieved great success in cancer immunotherapy, but their uncontrollable immune-related adverse events remain a major challenge. In this study, we developed a tumor-activated nanoparticle that is specifically active in tumors but not in normal tissues. We discovered a short anti-PD-L1 peptide that blocks the PD-1/PD-L1 interaction. The peptide was modified with a PEG chain through a novel matrix metalloproteinase-2 (MMP-2)-specific cleavage linker. The modified TR3 peptide self-assembles into a micelle-like nanoparticle (TR3-M-NP), which remains inactive and unable to block the PD-1/PD-L1 interaction in its native form. However, upon cleavage by MMP-2 in tumors, it releases the active peptide. The TR3-M-NP_5k nanoparticle was specifically activated in tumors through enzyme-mediated cleavage, leading to the inhibition of tumor growth and extended survival compared to control groups. In summary, TR3-M-NP shows great potential as a tumor-responsive immunotherapy agent with reduced toxicities.</div></div><div><h3>Statement of significance</h3><div>In this study, we developed a bioactive peptide-based checkpoint inhibitor that is active only in tumors and not in normal tissues, thereby potentially avoiding immune-related adverse effects. We discovered a short anti-PD-L1 peptide, TR3, that blocks the PD-1/PD-L1 interaction. We chemically modified the TR3 peptide to self-assemble into a micelle-like nanoparticle (TR3-M-NP), which itself cannot block the PD-1/PD-L1 interaction but releases the active TR3 peptide in tumors upon cleavage by MMP-2. In contrast, the nanoparticle is randomly degraded in normal tissues into peptides fragments that cannot block the PD-1/PD-L1 interaction. Upon intraperitoneal injection, TR3-M-NP_5k was activated specifically in tumors through enzyme cleavage, leading to the inhibition of tumor growth and extended survival compared to the control groups. In summary, TR3-M-NP holds significant promise as a tumor-responsive immunotherapy agent with reduced toxicities. The bioactive platform has the potential to be used for other types of checkpoint inhibitor.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 484-497"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883812","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":"Innovative perspectives on metal free contrast agents for MRI: Enhancing imaging efficacy, and AI-driven future diagnostics","authors":"Abdul Wahab ,&nbsp;Muhammad Suhail ,&nbsp;Tatiana Eggers ,&nbsp;Khurram Shehzad ,&nbsp;Ozioma Udochukwu Akakuru ,&nbsp;Zahoor Ahmad ,&nbsp;Zhichao Sun ,&nbsp;M. Zubair Iqbal ,&nbsp;Xiangdong Kong","doi":"10.1016/j.actbio.2025.01.005","DOIUrl":"10.1016/j.actbio.2025.01.005","url":null,"abstract":"<div><div>The U.S. Food and Drug Administration (FDA) has issued a boxed warning and mandated additional safety measures for all gadolinium-based contrast agents (GBCAs) used in clinical magnetic resonance imaging (MRI) due to their prolonged retention in the body and associated adverse health effects. This review explores recent advancements in CAs for MRI, highlighting four innovative probes: ORCAs, CEST CAs, ¹⁹F CAs, and HP ¹³C MRI. ORCAs offer a metal-free alternative that enhances imaging through nitroxides. CEST MRI facilitates the direct detection of specific molecules via proton exchange, aiding in disease diagnosis and metabolic assessment. ¹⁹F MRI CAs identify subtle biological changes, enabling earlier detection and tailored treatment approaches. HP ¹³C MRI improves visualization of metabolic processes, demonstrating potential in cancer diagnosis and monitoring. Finally, this review concludes by addressing the challenges facing the field and outlining future research directions, with a particular focus on leveraging artificial intelligence to enhance diagnostic capabilities and optimize both the performance and safety profiles of these innovative CAs.</div></div><div><h3>Statement of significance</h3><div>The review addresses the urgent need for safer MRI contrast agents in light of FDA warnings about GBCAs. It highlights the key factors influencing the stability and functionality of metal-free CAs and recent advancements in designing ORCAs, CEST CAs, 19F CAs, and HP ¹³C probes and functionalization that enhance MRI contrast. It also explores the potential of these agents for multimodal imaging and targeted diagnostics while outlining future research directions and the integration of artificial intelligence to optimize their clinical application and safety. This contribution is pivotal for driving innovation in MRI technology and improving patient outcomes in disease detection and monitoring.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 83-106"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967426","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}