Acta Biomaterialia最新文献

{"title":"Inhalation of macrophage membrane-coated hydrogel microparticles for inflammation alleviation of acute lung injury in vivo","authors":"Liang Song ,&nbsp;Zihe Zhai ,&nbsp;Wei Ouyang ,&nbsp;Jie Ding ,&nbsp;Shuqin Wang ,&nbsp;Shifen Li ,&nbsp;Min Liang ,&nbsp;Feng Xu ,&nbsp;Changyou Gao","doi":"10.1016/j.actbio.2024.12.015","DOIUrl":"10.1016/j.actbio.2024.12.015","url":null,"abstract":"<div><div>Hydrogel microparticles (HMPs) have many advantages for biomedical applications, particularly for minimally invasive therapy, for example, acute lung injury (ALI) that is characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators in the microenvironment. In this study, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were designed and prepared by using a membrane emulsification device. The HMPs were composed of double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal linkages and unsaturated double bonds. Surface-coating of inflammatory macrophage (M1) cell membranes was performed to obtain the membrane-coated HBPAK HMPs (mem HMPs) via electrostatic force. The mem HMPs exhibited strong ROS-scavenging and anti-inflammatory properties both <em>in vitro</em> and <em>in vivo</em>. After administered by inhalation in an ALI mouse model, the mem HMPs reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation. Our results suggest that the mem HMPs could serve as a potential therapeutic platform for treating inflammatory diseases with high efficiency.</div></div><div><h3>Statement of significance</h3><div>Hydrogel microparticles (HMPs) with minimally invasive delivery are advantageous for acute lung injury (ALI) characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators. Herein, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were prepared by copolymerizing double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal bonds and unsaturated double bonds in a membrane emulsification device. The HMPs covered with inflammatory macrophage (M1) cell membranes (mem HMPs) exhibited strong ROS-scavenging and anti-inflammation properties, reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 409-418"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796677","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":"Incorporation of metal-doped silicate microparticles into collagen scaffolds combines chemical and architectural cues for endochondral bone healing","authors":"Janina Stadter ,&nbsp;Andreas Hoess ,&nbsp;Hans Leemhuis ,&nbsp;Aaron Herrera ,&nbsp;Rebecca Günther ,&nbsp;Simone Cho ,&nbsp;Stephanie Diederich ,&nbsp;Gabriela Korus ,&nbsp;Richard Frank Richter ,&nbsp;Ansgar Petersen","doi":"10.1016/j.actbio.2024.12.029","DOIUrl":"10.1016/j.actbio.2024.12.029","url":null,"abstract":"<div><div>Regeneration of large bone defects remains a clinical challenge until today. While existing biomaterials are predominantly addressing bone healing via direct, intramembranous ossification (IO), bone tissue formation via a cartilage phase, so-called endochondral ossification (EO) has been shown to be a promising alternative strategy. However, pure biomaterial approaches for EO induction are sparse and the knowledge how material components can have bioactive contribution to the required cartilage formation is limited. Here, we combined a previously developed purely architecture-driven biomaterial approach with the release of therapeutic metal ions from tailored silicate microparticles. The delivery platform was free of calcium phosphates (CaP) that are known to support IO but not EO and was employed for the release of lithium (Li), magnesium (Mg), strontium (Sr) or zinc (Zn) ions. We identified an ion-specific cellular response in which certain metal ions strongly enhanced cell recruitment into the material and showed superior chondrogenesis and deposition collagen II by human mesenchymal stromal cells (MSCs). At the same time, in some cases microparticle incorporation altered the mechanical properties of the biomaterial with consequences for cell-induced biomaterial contraction and scaffold wall deformation. Collectively, the results suggest that the incorporation of metal-doped silicate microparticles has the potential to further improve the bioactivity of architectured biomaterials for bone defect healing via EO.</div></div><div><h3>Statement of significance</h3><div>Endochondral bone healing, a process that resembles embryonic skeletal development, has gained prominence in regenerative medicine. However, most therapeutic biomaterial strategies are not optimized for endochondral bone healing but instead target direct bone formation through IO. Here, we report on a novel approach to accelerate biomaterial-guided endochondral bone healing by combining cell-guiding collagen scaffolds with therapeutic metal-doped silicate microparticles. While other strategies, such as hypoxia-mimic drugs and iron-chelating biomaterials, have been documented in the literature before to enhance EO, our approach uniquely implements enhanced bioactivity into a previously developed biomaterial strategy for bone defect regeneration. Enhanced cell recruitment into the material and more pronounced chondrogenesis were observed for specific hybrid scaffold formulations, suggesting a high relevance of this new biomaterial for improved endochondral bone healing.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 260-278"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824977","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":"Super-hydrophilic and super-lubricating Zwitterionic hydrogel coatings coupled with polyurethane to reduce postoperative dura mater adhesions and infections","authors":"Hui Rong ,&nbsp;Shupeng Sun ,&nbsp;Manhua Lu ,&nbsp;Yiqun Zhang ,&nbsp;Lingyuan Liu ,&nbsp;Ziwei Guo ,&nbsp;Zimeng Zhang ,&nbsp;Zhanpeng Ye ,&nbsp;Jianhua Zhang ,&nbsp;Budong Chen ,&nbsp;Shuangyang Li ,&nbsp;Anjie Dong","doi":"10.1016/j.actbio.2024.12.038","DOIUrl":"10.1016/j.actbio.2024.12.038","url":null,"abstract":"<div><div>The dura trauma or large defects due to neurosurgical procedures can result in potential complications. Dural replacements have proven effective to reduce the risk of seizures, meningitis, cerebrospinal fluid leakage, cerebral herniation, and infection. Although various artificial dural patches have been developed, addressing iatrogenic infections and cerebral adhesions resulting from patches implantation remains a challenge. This study employed a network interpenetration modification strategy to introduce super-hydrophilic and super-lubricity zwitterionic hydrogel coatings on polyurethane Neuro-Patch® (NP®) dura mater patch. The successful modification with the hydrogel coating preserved the intrinsic properties of the NP®, such as their anti-leakage and tensile strength capabilities, while effectively reducing biofouling on the surface of the patches. Additionally, by constructing subdural implantation for each dura mater substitute in rabbits, we observed that artificial dura mater patches modified with the hydrogel coating effectively reduced the incidence of postoperative cerebral adhesions and infections. This suggests a promising application prospect of the hydrogel coating in dural repair.</div></div><div><h3>Statement of significance</h3><div>The development of dural substitutes with anti-leakage, anti-adhesion and anti-infection functions is the key to the treatment of dural defects and cerebrospinal fluid leakage during trauma or neurosurgery. In this study, the amphoteric ionic hydrogel coating was firmly modified on the surface of polyurethane with a mild modification process to give the patch super-hydrophilic and super-lubricating properties. The adhesion of non-specific proteins and bacteria is effectively reduced. The rabbit dural defect repair model showed that the introduction of zwitterionic hydrogel coating effectively reduced the occurrence of postoperative infection, and no tissue adhesion was observed. Taken together, this study offers a promising way to enhance the performance of artificial dural patches, potentially benefiting patients undergoing neurosurgery.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 206-217"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831190","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":"Mechanistic insights into mosquito antennal architecture for auditory adaptations","authors":"Adwait A. Trikanad ,&nbsp;Phani Saketh Dasika ,&nbsp;Hoover Pantoja-Sánchez ,&nbsp;Ximena E. Bernal ,&nbsp;Pablo D. Zavattieri","doi":"10.1016/j.actbio.2024.12.031","DOIUrl":"10.1016/j.actbio.2024.12.031","url":null,"abstract":"<div><div>Unlike organisms equipped with tympanal ears, mosquitoes hear using their antennae, which are lightweight sensory structures capable of detecting sound. Here, we study the antennae of two species — <em>Aedes aegypti</em> and <em>Uranotaenia lowii</em> — known to use hearing for different functions. Through the use of geometrically comprehensive computational models, we find that architectural features in the mosquito antenna provide mechanisms that promote the detection of species and sex specific acoustic targets amidst the non-target signals produced by their own wingbeats. Structurally, we find that the increased surface area of sensory hairs provides enhanced sensitivity while the tapering effect of intersegmental variation affects the tuning response. These features result in the highest antennal sensitivity through vibration at specific natural frequency modes that correspond to frequencies associated with their acoustic targets.</div></div><div><h3>Statement of Significance</h3><div>Our study provides valuable insights into the remarkable architectural design of mosquito antennae and its role in auditory adaptations. By dissecting the intricate geometry of antennal architecture in <em>Aedes aegypti</em> and <em>Uranotaenia lowii</em>, we uncover mechanisms that enhance sensitivity to specific acoustic cues while mitigating interference from wingbeat noise. This research builds upon and extends the existing understanding, providing a deeper comprehension of how mosquitoes navigate their acoustic environment. Our findings have significant implications for understanding sensory adaptations in insects and may inspire the development of bioinspired sensing technologies. We believe our work will interest a broad audience by offering new perspectives on the intersection of biomechanics and sensory biology, which can also find applications in the design of bioinspired architected materials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 165-174"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824613","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":"TEVAR versus open aortic arch replacement in ex vivo perfused human thoracic aortas","authors":"Masoud Yusefi ,&nbsp;Emmanouil Agrafiotis ,&nbsp;Peter Regitnig ,&nbsp;Günther Laufer ,&nbsp;Gerhard Sommer ,&nbsp;Gerhard A. Holzapfel ,&nbsp;Heinrich Mächler","doi":"10.1016/j.actbio.2024.12.019","DOIUrl":"10.1016/j.actbio.2024.12.019","url":null,"abstract":"&lt;div&gt;&lt;div&gt;This study aims to assess the outcomes of therapeutic options for aortic arch pathologies by comparing thoracic endovascular aortic repair (TEVAR) with open arch replacement (OAR) using woven polyester grafts from a mechanical and biomechanical perspective, with emphasis on &lt;em&gt;ex vivo&lt;/em&gt; perfused human thoracic aortas reproducing heart rate and stroke volume conditions. Eleven non-diseased thoracic aortas from human cadavers were divided into TEVAR (&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;n&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mn&gt;5&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;) and OAR (&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;n&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mn&gt;6&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;) and tested using a custom-built mock circulation loop. Pressure, diameter, and stroke volume were monitored during perfusion before and after the intervention. Samples undergoing TEVAR showed a higher ascending systolic pressure post-intervention than OAR (TEVAR: &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mn&gt;137&lt;/mn&gt;&lt;mo&gt;±&lt;/mo&gt;&lt;mn&gt;9&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; &lt;!--&gt; &lt;!--&gt;mmHg vs OAR: &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mn&gt;126&lt;/mn&gt;&lt;mo&gt;±&lt;/mo&gt;&lt;mn&gt;6&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; &lt;!--&gt; &lt;!--&gt;mmHg, &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;p&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;017&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;). After the intervention, a significant discrepancy in the mean pressure differences between the ascending and descending aorta &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;Δ&lt;/mi&gt;&lt;mi&gt;P&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; was observed (TEVAR: &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mn&gt;9&lt;/mn&gt;&lt;mo&gt;±&lt;/mo&gt;&lt;mn&gt;3&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; &lt;!--&gt; &lt;!--&gt;mmHg vs OAR: &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mo&gt;±&lt;/mo&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; &lt;!--&gt; &lt;!--&gt;mmHg, &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;p&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;004&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;). Input impedance at zero frequency, approximating Windkessel resistance, was higher for TEVAR than for OAR (TEVAR: &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;78&lt;/mn&gt;&lt;mo&gt;±&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;04&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; vs OAR: &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;66&lt;/mn&gt;&lt;mo&gt;±&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;03&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; &lt;!--&gt; &lt;!--&gt;mmHg&lt;!--&gt; &lt;!--&gt;s/ml, &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;p&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;004&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;). A correlation was found between the resistance and the negative peak of the time-normalized wave intensity analysis (Kendall’s coefficient &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;τ&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;35&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; and &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;p&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;023&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;). Another correlation was observed between resistance and &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;Δ&lt;/mi&gt;&lt;mi&gt;P&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; (&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;τ&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;51&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;, &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;p&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;mo&gt;.&lt;/mo&gt;&lt;mn&gt;001&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;). Looking at the replication of heart rate and stroke volume over the course of the study, the observed differences can largely be attributed to the type of intervention. The results suggest that TEVAR has adverse effects compared to OAR, particu","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 140-150"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824773","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":"Sequential delivery of cardioactive drugs via microcapped microneedle patches for improved heart function in post myocardial infarction rats","authors":"Fengpu He ,&nbsp;Syed Muntazir Andrabi ,&nbsp;Haiwang Shi ,&nbsp;Yura Son ,&nbsp;Huiliang Qiu ,&nbsp;Jingwei Xie ,&nbsp;Wuqiang Zhu","doi":"10.1016/j.actbio.2024.12.009","DOIUrl":"10.1016/j.actbio.2024.12.009","url":null,"abstract":"<div><div>After myocardial infarction, the heart undergoes adverse remodeling characterized by a series of pathological changes, including inflammation, apoptosis, fibrosis, and hypertrophy. In addition to cardiac catheter-based re-establishment of blood flow, patients typically receive multiple medications that aim to address these different mechanisms underlying left ventricular remodeling. The current study aims to establish a versatile multi-drug delivery platform for the controlled and sequential delivery of multiple therapeutic agents in a single treatment. Toward this goal, we generated a microcapped microneedle patch carrying methylprednisolone, interleukin-10, and vascular endothelial growth factor. In vitro characterization demonstrated a time-sequenced release pattern of these drug: methylprednisolone for the first 3 days, interleukin-10 from day 1 to 15, and vascular endothelial growth factor from day 3 to 25. The therapeutic effects of the microneedle patch were evaluated in a rat model of acute myocardial infarction induced by permanent ligation of left anterior descending coronary artery. Heart function was measured using trans-thoracic echocardiography. Heart inflammation, apoptosis, hypertrophy and angiogenesis were evaluated using histology. Our data indicated that, at 28 days after patch transplantation, animals receiving the microneedle patch with sequential release of these three agents showed reduced inflammation, apoptosis and cardiac hypertrophy compared to the animals receiving control patch without sequential release of these agents, which is associated with the improved angiogenesis and heart function. In conclusion, the microneedle patch can be utilized to deliver multiple therapeutic agents in a controlled and sequential manner that aligns with the pathological phases following myocardial infarction.</div></div><div><h3>Statement of significance</h3><div>The post-myocardial infarction heart remodeling is characterized by a series of pathological events including acute inflammation, apoptosis, fibrosis, cardiac hypertrophy, and depressed heart function. In current clinical practice, multiple procedures and drugs given at different time points are necessary to combat these series of pathological events. In this study, we developed a novel microcapped microneedle patch for the controlled sequential delivery of triple cardioprotective drugs aiming to combat acute inflammation and cardiac hypertrophy, and promote angiogenesis. This study presents a comprehensive therapeutic approach, with the microneedle patch addressing multifaceted pathological processes during post-myocardial infarction left ventricular remodeling. This cardiac drug delivery system has the potential to improve patient treatment by delivering drugs in alignment with the series of time-dependent pathological phases following myocardial infarction, ultimately improving clinical outcomes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 235-247"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792974","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":"X-ray triggered bimetallic nanoassemblies as radiosensitizers and STING agonists for a CDT/radio-immunotherapy strategy","authors":"Ruifang Chen ,&nbsp;Jinglang Gong ,&nbsp;Ziyi Yu ,&nbsp;Xiyao Wu ,&nbsp;Changjun Li ,&nbsp;Yiling Ruan ,&nbsp;Shouju Wang ,&nbsp;Xiaolian Sun","doi":"10.1016/j.actbio.2024.12.030","DOIUrl":"10.1016/j.actbio.2024.12.030","url":null,"abstract":"<div><div>Radiotherapy (RT) is a cornerstone of cancer therapy, but its effectiveness is constrained by dose-limiting toxicity and inadequate systemic immune activation. To overcome these limitations, we have engineered an X-ray-responsive nanoassembly (sMnAu NAs) by cross-linking monodisperse MnAu nanoparticles (NPs) with radiation-responsive diselenide-containing linkers. MnAu alloy NPs not only provide Au NPs for radiosensitization, but also control Mn (0) release, which stimulates Fenton-like reaction for chemodynamic therapy and is transferred into Mn²⁺ to activate the STING pathway for immunotherapy. The responsive design not only improves tumor accumulation <em>via</em> EPR effect during circulation, but also achieves deep penetration of MnAu NPs following X-ray induced disassembly. The synergistic combination of chemodynamic therapy, radiotherapy and immunotherapy exhibits remarkable inhibition of tumor growth and metastasis. Overall, our sMnAu NAs represent a promising radiosensitizer for chemodynamic therapy and radiotherapy to enhance immunotherapy.</div></div><div><h3>Statement of Significance</h3><div>As a principal treatment modality in cancer management, RT is limited due to the co-irradiation of organs at risk and subsequent normal tissue toxicities. This study reported an X-ray responsive radiosensitizer prepared by cross-linking monodisperse MnAu NPs with diselenide-containing linkers. Upon X-ray irradiation, sMnAu NAs accumulate in tumors and disassemble into MnAu NPs, enabling deeper penetration. The increased surface area of MnAu NPs enhances the exposure of Mn(0), which reacts into Mn²⁺ and enhances ROS generation. The released Mn²⁺ activates the STING pathway, potentiating the X-ray-induced immune response. The synergistic integration of CDT, RT, and immunotherapy results in a potent suppression of tumor growth and metastasis. Collectively, this X-ray activatable CDT/radio-immunotherapy strategy holds great potential for effective cancer treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 366-376"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824784","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":"Dhvar5- and MSI78-coated titanium are bactericidal against methicillin-resistant Staphylococcus aureus, immunomodulatory and osteogenic","authors":"B. Costa ,&nbsp;J. Coelho ,&nbsp;V. Silva ,&nbsp;H. Shahrour ,&nbsp;N.A. Costa ,&nbsp;A.R. Ribeiro ,&nbsp;S.G. Santos ,&nbsp;F. Costa ,&nbsp;G. Martínez-de-Tejada ,&nbsp;C. Monteiro ,&nbsp;M.C.L. Martins","doi":"10.1016/j.actbio.2024.11.016","DOIUrl":"10.1016/j.actbio.2024.11.016","url":null,"abstract":"<div><div>Infection is one of the major issues associated with the failure of orthopedic devices, mainly due to implant bacterial colonization, biofilm formation, and associated antibiotic resistance. Antimicrobial peptides (AMP) are a promising alternative to conventional antibiotics given their broad-spectrum of activity, low propensity to induce bacterial resistance, and ability to modulate host immune responses. Dhvar5 (LLLFLLKKRKKRKY) and MSI78 (GIGKFLKKAKKFGKAFVKILKK) are two AMP with broad-spectrum activity against bacteria, including methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), one of the most problematic etiologic agents in Orthopedic Devices-Related Infections (ODRI). This work aims to evaluate the bactericidal, immunomodulatory and osteogenic potential of Dhvar5- and MSI78-coated titanium surfaces (AMP-Ti). Two AMP-Ti surfaces were successfully obtained by grafting Dhvar5 (0.8 ± 0.1 µM/mm²) or MSI78 (0.5 ± 0.3 µM/mm²) onto titanium substrates through a polydopamine layer. Both AMP-Ti were bactericidal against MRSA, eradicating bacteria upon contact for 6 h in a culture medium supplemented with human plasma proteins. The AMP-Ti immunomodulatory potential was evaluated using human primary macrophages, by assessing surfaces capacity to induce pro-/anti-inflammatory (M1/M2) markers and cytokines. While in naïve conditions both AMP-Ti surfaces slightly promoted the M2 marker CD163, in response to LPS and IFN-γ (simulating a bacterial infection), both AMP increased the M1 marker CCR7 and enhanced macrophage secretion of pro-inflammatory IL-6 and TNF-α cytokines, particularly for Ti-MSI78 surfaces. Additionally, both AMP-Ti surfaces were cytocompatible and promoted osteoblastic cell differentiation. This proof-of-concept study demonstrated the high potential of Dhvar5- and MSI78-Ti as antimicrobial coatings for ODRI prevention.</div></div><div><h3>Statement of significance</h3><div>This study investigates the bactericidal effects of the antimicrobial peptides Dhvar5 and MSI78, immobilized on titanium (Ti) surfaces through a polydopamine coating, aiming at the prevention of Orthopedic-Device Related Infections (ODRIs). The developed coatings displayed MRSA-sterilizing activity, while revealing an immunomodulatory potential towards macrophages and promoting osteoblastic cell differentiation. This strategy allows a quick and easy immobilization of high quantities of AMP, unlike most other approaches, thus favoring its clinical translation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 98-112"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634032","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":"Incorporation of cerium oxide nanoparticles into the micro-arc oxidation layer promotes bone formation and achieves structural integrity in magnesium orthopedic implants","authors":"Guan-Lin Wu ,&nbsp;Chin-En Yen ,&nbsp;Wei-Chien Hsu ,&nbsp;Ming-Long Yeh","doi":"10.1016/j.actbio.2024.11.008","DOIUrl":"10.1016/j.actbio.2024.11.008","url":null,"abstract":"<div><div>Biodegradable metals offer significant advantages by reducing the need for additional surgeries following bone fixation. These materials, with their optimal mechanical and degradable properties, also mitigate stress-shielding effects while promoting biological processes essential for healing. This study investigated the in vitro and in vivo biocompatibility of ZK60 magnesium alloy coated with a micro-arc oxidative layer incorporated with cerium oxide nanoparticles in orthopedic implants. The results demonstrated that the magnesium substrate undergoes gradual degradation, effectively eliminating long-term inflammation during bone formation. The micro-arc oxidative coating forms a dense ceramic layer, acting as a protective barrier that reduces corrosion rates and enhances the biocompatibility of the magnesium substrate. The incorporation of cerium oxide nanoparticles improves the tribological properties of the coating, refining degradation patterns and improving osteogenic characteristics. Furthermore, cerium oxide nanoparticles enhance bone reconstruction by facilitating appropriate interconnections between newly formed bone and native bone tissue. Consequently, cerium oxide nanoparticles contribute to favorable biosafety outcomes and exceptional bone remodeling capabilities by supporting bone healing and sustaining a prolonged degradation process, ultimately achieving dynamic equilibrium in bone formation.</div></div><div><h3>Statement of significance</h3><div>This study comprehensively examined the incorporation of cerium oxide nanoparticles into biodegradable magnesium through a micro-arc oxidative process for use in orthopedic implants. This study conducted a comprehensive analysis involving material characterization, biodegradability testing, in vitro osteogenesis assays, and in vivo implantation, highlighting the potential benefits of the distinctive properties of cerium oxide nanoparticles. This research emphasizes the ability of cerium oxide nanoparticles to enhance the biodegradability of magnesium and facilitate remarkable bone regeneration, suggesting promising advantages for additive materials in orthopedic implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 80-97"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634137","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":"Engineering a nano-drug delivery system to regulate m6A modification and enhance immunotherapy in gastric cancer","authors":"Zhengshuo Li ,&nbsp;Xiaoyue Zhang ,&nbsp;Can Liu ,&nbsp;Yangge Wu ,&nbsp;Yuqing Wen ,&nbsp;Run Zheng ,&nbsp;Chenxiao Xu ,&nbsp;Junrui Tian ,&nbsp;Qiu Peng ,&nbsp;Xiang Zheng ,&nbsp;Jia Wang ,&nbsp;Qun Yan ,&nbsp;Lingyu Wei ,&nbsp;Jian Ma","doi":"10.1016/j.actbio.2024.11.036","DOIUrl":"10.1016/j.actbio.2024.11.036","url":null,"abstract":"<div><div>Cancer cell membrane-derived nanoparticle drug delivery system enables precise drug delivery to tumor tissues and is a new effective way to treat solid tumors. The aim of this study is to develop a safe and effective cancer cell membrane-derived nano-delivery system targeting gastric cancer. We previously reported that EPH receptor A2 (EphA2) is an important target for gastric cancer. RNA m6A methyltransferases METTL3 is upregulated in multiple cancers and promotes cancer development by increasing the expression of multiple oncogenes. We design a new nano-delivery system PLGA-STM-TAT: nanoparticles PLGA (poly lactic acid-hydroxyacetic acid) loaded with METTL3 inhibitor STM2457 and cell-penetrating peptide TAT, and then covered with gastric cancer cell membranes equipped with YSA peptides by means of click chemistry, which targeting EphA2. The nanoparticles are specifically enriched in gastric cancer tissues, significantly increased drug accumulation, and inhibited cancer cell proliferation by decreasing key oncogenes c-MYC and BRD4. During drug administration, we found that the expression of the immune checkpoint molecule PD-L1 was suppressed, and the anti-tumor immune effect was enhanced by the nano-delivery system in combination with anti-PD1. This cancer cell membrane-derived nano-delivery system provides a new biological strategy to treat gastric cancer through effective m6A modulation and EphA2 targeting.</div></div><div><h3>Statement of significance</h3><div>M6A modifications have important biological roles, especially in tumors. Targeting highly modified m6A in gastric cancer becomes a challenge. We developed a nano-drug delivery system for modulating m6A that could produce an effective anti-cancer therapeutic effect and that the nanoparticles enhanced antitumor immunity when combined with anti-PD1.This cancer cell membrane-derived new nano-drug delivery system shows great promise as an antitumor approach by modulating m6A modification and targeting EphA2 in gastric cancers.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 412-427"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712184","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}