Acta Biomaterialia最新文献

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Sequential delivery of cardioactive drugs via microcapped microneedle patches for improved heart function in post myocardial infarction rats 通过微帽微针贴片序贯给药改善心肌梗死后大鼠心功能。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-15 DOI: 10.1016/j.actbio.2024.12.009
Fengpu He , Syed Muntazir Andrabi , Haiwang Shi , Yura Son , Huiliang Qiu , Jingwei Xie , Wuqiang Zhu
{"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}
引用次数: 0
X-ray triggered bimetallic nanoassemblies as radiosensitizers and STING agonists for a CDT/radio-immunotherapy strategy X 射线触发双金属纳米组件作为 CDT/放射免疫疗法战略的放射增敏剂和 STING 激动剂。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-15 DOI: 10.1016/j.actbio.2024.12.030
Ruifang Chen , Jinglang Gong , Ziyi Yu , Xiyao Wu , Changjun Li , Yiling Ruan , Shouju Wang , Xiaolian Sun
{"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 Mn<sup>2+</sup> 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 Mn<sup>2+</sup> and enhances ROS generation. The released Mn<sup>2+</sup> 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}
引用次数: 0
Dhvar5- and MSI78-coated titanium are bactericidal against methicillin-resistant Staphylococcus aureus, immunomodulatory and osteogenic Dhvar5- 和 MSI78 涂层钛对耐甲氧西林金黄色葡萄球菌具有杀菌、免疫调节和成骨作用。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.016
B. Costa , J. Coelho , V. Silva , H. Shahrour , N.A. Costa , A.R. Ribeiro , S.G. Santos , F. Costa , G. Martínez-de-Tejada , C. Monteiro , M.C.L. Martins
{"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/mm<sup>2</sup>) or MSI78 (0.5 ± 0.3 µM/mm<sup>2</sup>) 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}
引用次数: 0
Incorporation of cerium oxide nanoparticles into the micro-arc oxidation layer promotes bone formation and achieves structural integrity in magnesium orthopedic implants 在微弧氧化层中加入氧化铈纳米粒子可促进骨形成,并实现镁骨科植入物的结构完整性。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.008
Guan-Lin Wu , Chin-En Yen , Wei-Chien Hsu , Ming-Long Yeh
{"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}
引用次数: 0
Engineering a nano-drug delivery system to regulate m6A modification and enhance immunotherapy in gastric cancer 利用纳米给药系统调节胃癌中的 m6A 修饰并加强免疫疗法。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.036
Zhengshuo Li , Xiaoyue Zhang , Can Liu , Yangge Wu , Yuqing Wen , Run Zheng , Chenxiao Xu , Junrui Tian , Qiu Peng , Xiang Zheng , Jia Wang , Qun Yan , Lingyu Wei , Jian Ma
{"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}
引用次数: 0
Expansion limits of meshed split-thickness skin grafts 网状裂厚植皮的扩张极限。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.038
Haomin Yu , Mohammad Jafari , Aliza Mujahid , Chelsea F Garcia , Jaisheel Shah , Riya Sinha , Yuxuan Huang , Delaram Shakiba , Yuan Hong , Danial Cheraghali , John R.S. Pryce , Jacob A. Sandler , Elliot L. Elson , Justin M. Sacks , Guy M. Genin , Farid Alisafaei
{"title":"Expansion limits of meshed split-thickness skin grafts","authors":"Haomin Yu ,&nbsp;Mohammad Jafari ,&nbsp;Aliza Mujahid ,&nbsp;Chelsea F Garcia ,&nbsp;Jaisheel Shah ,&nbsp;Riya Sinha ,&nbsp;Yuxuan Huang ,&nbsp;Delaram Shakiba ,&nbsp;Yuan Hong ,&nbsp;Danial Cheraghali ,&nbsp;John R.S. Pryce ,&nbsp;Jacob A. Sandler ,&nbsp;Elliot L. Elson ,&nbsp;Justin M. Sacks ,&nbsp;Guy M. Genin ,&nbsp;Farid Alisafaei","doi":"10.1016/j.actbio.2024.11.038","DOIUrl":"10.1016/j.actbio.2024.11.038","url":null,"abstract":"<div><div>Split-thickness skin grafts are widely used to treat chronic wounds. Procedure design requires surgeons to predict how much a patch of the patient's own skin expands when it is meshed with rows of slits and stretched over a larger wound area. Accurate prediction of graft expansion remains a challenge, with current models overestimating the actual expansion, leading to suboptimal outcomes. Inspired by the principles of mechanical metamaterials, we developed a model that distinguishes between the kinematic rearrangement of structural elements and their stretching, providing a more accurate prediction of skin graft expansion. Our model was validated against extensive data from skin graft surgeries, demonstrating vastly superior predictive capability compared to existing methods. This metamaterial-inspired approach enables informed decision-making for potentially improving healing outcomes.</div></div><div><h3>Statement of Significance</h3><div>Accurately predicting the expansion of meshed skin grafts is crucial for minimizing patient trauma and optimizing healing outcomes in reconstructive surgery. However, current quantitative models, which treat grafts as tessellated trusses of rigid bars, fail to accurately estimate graft expansion. We have uncovered the mechanisms underlying skin graft expansion and developed a straightforward method based on these findings. This method, designed for practical use by surgeons, provides accurate predictions of graft expansion, as validated against extensive data from skin graft surgeries.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 325-335"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712194","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}
引用次数: 0
Decellularized porcine dermal hydrogel enhances implant-based wound healing in the setting of irradiation 脱细胞猪真皮水凝胶可增强辐照环境下植入伤口的愈合。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.009
Lillian DeCostanza , Graham M. Grogan , Anthony C. Bruce , Corrina M. Peachey , Evan A. Clark , Kristen Atkins , Tina Tylek , Michael D. Solga , Kara L. Spiller , Shayn M. Peirce , Christopher A. Campbell , Patrick S. Cottler
{"title":"Decellularized porcine dermal hydrogel enhances implant-based wound healing in the setting of irradiation","authors":"Lillian DeCostanza ,&nbsp;Graham M. Grogan ,&nbsp;Anthony C. Bruce ,&nbsp;Corrina M. Peachey ,&nbsp;Evan A. Clark ,&nbsp;Kristen Atkins ,&nbsp;Tina Tylek ,&nbsp;Michael D. Solga ,&nbsp;Kara L. Spiller ,&nbsp;Shayn M. Peirce ,&nbsp;Christopher A. Campbell ,&nbsp;Patrick S. Cottler","doi":"10.1016/j.actbio.2024.11.009","DOIUrl":"10.1016/j.actbio.2024.11.009","url":null,"abstract":"<div><div>Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in implant-based breast reconstruction, and has shown to modulate the healing response. However, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective biomaterial integration requires regulating the immune response, fibrosis, and adipocyte-driven functionalization. Extracellular matrix (ECM) hydrogels have demonstrated utility in tissue regeneration, and decreasing inflammation and fibrosis in various tissues. Therefore, we hypothesized that a Decellularized Porcine Dermal (DPD) hydrogel to support ADM integration would prevent excessive fibrosis, regulate the macrophage response, and promote adipogenesis. Exploration of DPD hydrogel during ADM implantation in mice (healthy and radiated) revealed long-term effects of irradiation on implant wound healing. DPD hydrogel rescued radiation-induced fibrosis, restoring capsule thickness of healthy mice, and did not increase the fibroblast migration into the ADM. As a modulating soft tissue filler, DPD hydrogel also promoted adipocyte infiltration in healthy and irradiated mice. Detailed macrophage analysis showed that radiation led to the increase in pro-inflammatory, transition, and reparative markers. Despite relatively subtle effects on individual macrophage phenotype markers, multidimensional flow cytometry analysis revealed that DPD hydrogel temporally regulated two subpopulations. he presence of DPD resulted in significantly reduced CD9<sup>Hi</sup>Arg1<sup>Hi</sup>CD301b<sup>Lo</sup> and CD163<sup>Hi</sup>CD38<sup>Hi</sup>CD301b<sup>Hi</sup> macrophages in healthy mice at one week, and a significant increase in CD9<sup>High</sup> macrophages with low expression of other markers at 6 weeks in irradiated mice. DPD hydrogel promotes a decreased fibrotic, and adipocyte-promoting coordination of wound healing in healthy and irradiated wound beds while not disrupting the immunomodulatory effects of ADM.</div></div><div><h3>Statement of significance</h3><div>Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in post-mastectomy implant-based breast reconstruction, and positively affects wound healing. Following breast reconstruction, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective wound healing and biomaterial integration requires regulating the cellular immune response. Extracellular matrix hydrogels have demonstrated utility in tissue regeneration and decreasing inflammation and fibrosis in various tissues, but has yet to be utilized in the setting of breast reconstruction. Here, we demonstrated that a decellularized dermal hydrogel as an adjunct to ADM, decreases fibrosis and promotes adipogenesis during the coordination of wound healing in healthy and clinically relevant microenvironments that have received radiation therapy while not disrupting the immunomodulatory effects of implanted ADM.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 260-275"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634125","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}
引用次数: 0
In vitro corrosion and biocompatibility of additively manufactured biodegradable molybdenum 添加剂制造的可生物降解钼的体外腐蚀性和生物相容性。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.019
Zhipei Tong , Gencheng Gong , He Huang , Guixing Cai , Liudang Fang , Hui Yu , Chuanqiang Li , Yufeng Zheng , Dong Bian
{"title":"In vitro corrosion and biocompatibility of additively manufactured biodegradable molybdenum","authors":"Zhipei Tong ,&nbsp;Gencheng Gong ,&nbsp;He Huang ,&nbsp;Guixing Cai ,&nbsp;Liudang Fang ,&nbsp;Hui Yu ,&nbsp;Chuanqiang Li ,&nbsp;Yufeng Zheng ,&nbsp;Dong Bian","doi":"10.1016/j.actbio.2024.11.019","DOIUrl":"10.1016/j.actbio.2024.11.019","url":null,"abstract":"<div><div>Recently, molybdenum (Mo) has been recognized a promising biodegradable metal, however, it is difficult to be processed through traditional deformation or machining due to its high strength &amp; hardness. Additive manufacturing is a good way to get rid of this dilemma. Here, Mo components were directly fabricated with fine Mo powder through selective laser melting (SLM). Microstructure, <em>in-vitro</em> corrosion behaviors and biocompatibility of the as-obtained Mo were thoroughly investigated. Compared to Mo fabricated through rotary swaging (RS), ineluctable hot cracks were found in SLMed bulk Mo, and those defects accelerated the initial ion release rate (1.31 μg·mL<sup>−1</sup>·d<sup>−1</sup> during the first week, one order of magnitude higher than that of RSed Mo). The unique SLMed microstructure resulted in different surface chemical components, constituent phases and corrosion layer structures, thus leading to a different corrosion mode and corrosion evolution along with time. SLMed Mo exhibited good hemocompatibility, and mouse/rat-derived mesenchymal stem cells have certain tolerance to soluble Mo in the sample extracts. However, the deteriorative surface condition on SLMed Mo impaired its biocompatibility to directly attached cells. Cells could adhere onto SLMed Mo, however their proliferation and spreading were impaired along with further corrosion. Additive manufacturing is a powerful tool to fabricate Mo based structural parts, however, the issue of microstructural defects should be well resolved. Close attention should be paid to the hot-cracks and accompanied fast &amp; non-uniform corrosion.</div></div><div><h3>Statement of Significance</h3><div>Additive manufacturing is a good way to fabricate implants based on refractory and un-processable biodegradable metals. Here, Mo components were directly fabricated with Mo powder through selective laser melting (SLM). Microstructure, <em>in-vitro</em> corrosion behaviors and biocompatibility of the as-obtained Mo were thoroughly investigated. Compared to Mo fabricated through traditional rotary swaging (RS), the unique SLMed microstructure resulted in different corrosion mode and corrosion evolution along with time. Localized corrosion appeared at the micro-cracks in SLMed samples, thus leading to a 10-fold ion release at week 1. Cells could adhere onto SLMed Mo, however their proliferation and spreading were impaired along with further corrosion. Close attention should be paid to the hot-cracks and accompanied fast &amp; non-uniform corrosion.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 66-79"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689827","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}
引用次数: 0
Construction of piezoelectric, conductive and injectable hydrogels to promote wound healing through electrical stimulation 构建压电、导电和可注射水凝胶,通过电刺激促进伤口愈合。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.028
Yunyun Wu , Yanjing Wang , Weili Li , Diyi Li , Panpan Song , Yaqing Kang , Xiaoqing Han , Xinbo Wang , Hongkun Tian , Abdur Rauf , Jiao Yan , Haiyuan Zhang , Xi Li
{"title":"Construction of piezoelectric, conductive and injectable hydrogels to promote wound healing through electrical stimulation","authors":"Yunyun Wu ,&nbsp;Yanjing Wang ,&nbsp;Weili Li ,&nbsp;Diyi Li ,&nbsp;Panpan Song ,&nbsp;Yaqing Kang ,&nbsp;Xiaoqing Han ,&nbsp;Xinbo Wang ,&nbsp;Hongkun Tian ,&nbsp;Abdur Rauf ,&nbsp;Jiao Yan ,&nbsp;Haiyuan Zhang ,&nbsp;Xi Li","doi":"10.1016/j.actbio.2024.11.028","DOIUrl":"10.1016/j.actbio.2024.11.028","url":null,"abstract":"<div><div>Piezoelectric, conductive, and injectable hydrogel (SPG hydrogel) is constructed to rapidly close wounds, efficiently harvest biomechanical energy from animal motion, and generate electrical stimulation for electrotherapy of wound healing. 3-amino-4-methoxybenzoic acid (AMB) monomer was polymerized and grafted onto the gelatin, which was further crosslinked using EDC/NHS and embedded with strontium titanate nanoparticles (80.5 wt%), forming SPG hydrogel. This SPG hydrogel had high tissue adhesion ability, and could generate the output voltage (maximum output voltage 1 V) and current (maximum output current 0.5 nA) upon mechanical bending, promoting NIH-3T3 cell migration and proliferation. Upon application to the mice wound model, the SPG hydrogel rapidly closed the skin wound, smoothed the wound's appearance, reduced the remaining wound size, and increased epidermal thickness, demonstrating remarkable wound healing capabilities. This study suggests that the body motion-promoted electrotherapy offers a promising strategy for wound healing.</div></div><div><h3>Statement of significance</h3><div>Piezoelectric nanomaterials are often incorporated into hydrogels to create piezoelectric hydrogels for wound healing. However, piezoelectric nanomaterials tend to agglomerate within the hydrogel matrix, and the hydrogel's low conductivity hinders efficient electron transfer. Together, both factors significantly reduce the piezoelectric effect. In this study, we developed an SPG hydrogel to improve the homogeneity and conductivity of the piezoelectric hydrogel. We first designed a conductive PG hydrogel and then immoblized piezoelectric STO nanoparticles within its matrix through coordination chemistry. Upon mechanical deformation, the uniformly distributed STO nanoparticles can generate electricity, which can efficiently transfer through the conductive matrix to the hydrogel's surface. This design shows great potential for wound healing applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 205-215"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694023","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}
引用次数: 0
Multi-phoretic nanomotor with consistent motion direction for enhanced cancer therapy 具有一致运动方向的多流体纳米马达,用于增强癌症治疗。
IF 9.4 1区 医学
Acta Biomaterialia Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.037
Wei Zhang , Yangyang Xiang , Qi Guo , Xiaotong Wang , Lukai Zhang , Jiaxin Guo , Ridong Cong , Wei Yu , Xing-Jie Liang , Jinchao Zhang , Dandan Liu
{"title":"Multi-phoretic nanomotor with consistent motion direction for enhanced cancer therapy","authors":"Wei Zhang ,&nbsp;Yangyang Xiang ,&nbsp;Qi Guo ,&nbsp;Xiaotong Wang ,&nbsp;Lukai Zhang ,&nbsp;Jiaxin Guo ,&nbsp;Ridong Cong ,&nbsp;Wei Yu ,&nbsp;Xing-Jie Liang ,&nbsp;Jinchao Zhang ,&nbsp;Dandan Liu","doi":"10.1016/j.actbio.2024.11.037","DOIUrl":"10.1016/j.actbio.2024.11.037","url":null,"abstract":"<div><div>Nanomotors have emerged as promising candidates for the deep penetration of loaded drugs into cancer stem cells (CSCs) located within the core of tumor tissues. A crucial factor in maximizing the clinical potential of nanomotors lies in their ability to respond dynamically to various stimuli in the tumor microenvironment. By adjusting their propulsion mechanisms in response to various stimuli, nanomotors can maintain directional movement, thus improving drug distribution and therapeutic efficacy. In this study, we present the design of a pH-responsive multi-phoretic propelled Janus nanomotor, comprising a SiO<sub>2</sub>@Pt core@shell nanosphere and half-wrapped acrylic acid polymers (PAA)-conjugated gold (Au) nanoparticles (JMSNs@Pt@P-Au). The JMSNs@Pt@P-Au catalyze endogenous H<sub>2</sub>O<sub>2</sub> into O<sub>2</sub>, propelling the nanomotors into solid tumors. Within the tumor microenvironment, the contraction of PAA triggers contact between the Au and Pt layers, facilitating self-electrophoresis propulsion. Simultaneously, a local thermal gradient is generated on the Au layer under near-infrared light irradiation, propelling the nanomotor through thermophoresis. Exploiting the unique structure of JMSNs@Pt@P-Au, the driving forces generated by H<sub>2</sub>O<sub>2</sub> catalysis, self-electrophoresis, and thermophoresis exhibit consistent motion directions. This consistency not only provides thrust for deep penetration but also enhances their targeted therapeutic efficiency against CSCs <em>in vivo</em>. This combination of nanomotor-driven power sources holds significant potential for designing intelligent, active drug delivery systems for effective CSC-targeted cancer therapy.</div></div><div><h3>Statement of Significance</h3><div>Deep penetration of nanomedicine in solid tumor tissue and cells is still an important challenge that restricts the therapeutic effect. Multiple-propelled nanomotors have been confirmed to be self-propulsive that overcome the limited penetration in solid tumor. However, their effective translation toward clinical applications is limited due to the inability to alter their propelled mechanisms in response to the actual physiological environment, resulting in speed and inconsistent movement directions. In this work, we designed a multi-phoretic propelled Janus nanomotor (JMSNs@Pt@P-Au) that exhibited three propelled mechanisms in response to the changes of pH value. Noteworthy is their heightened speed and remarkable tumor tissue penetration observed <em>in vitro</em> and <em>in vivo</em> without adverse effects. Such multi-phoretic propulsion offers considerable promise for developing advanced nanomachines with a stimuli-responsive switch of propulsion modes in biomedical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 352-368"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717730","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}
引用次数: 0
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