Acta Biomaterialia最新文献

{"title":"Perfluorohexane nanodroplet-assisted mechanical high intensity focused ultrasound cavitation: A strategy for hepatocellular carcinoma treatment","authors":"Jie Yang ,&nbsp;Min Liao ,&nbsp;Zhenru Wu ,&nbsp;Xiaodi Liu ,&nbsp;Zhiwen Zheng ,&nbsp;Wenhui Wang ,&nbsp;Zhe Wu ,&nbsp;Qiang Lu","doi":"10.1016/j.actbio.2025.01.061","DOIUrl":"10.1016/j.actbio.2025.01.061","url":null,"abstract":"<div><div>The activation of immune-stimulatory molecules is critical for effective antitumor immunotherapy. Mechanical high-intensity focused ultrasound (mHIFU) sustains this activation in tumor cell debris through cavitation. To enhance cavitation, perfluorohexane nanodroplets (NDs-PFH) were utilized in this study to lower the cavitation threshold during mHIFU ablation. Our results showed that NDs-PFH combined with mHIFU induced 77.2 % Hepa 1–6 tumor cells death, and activated the release of damage-associated molecular patterns (such as HMGB1, CRT, and ATP), enhancing dendritic cell maturation (20.2 %) and <em>T</em> cell activation (1.8 % of TNF-α⁺ and 2.7 % of IFN-γ⁺). In vivo<em>,</em> the combination of NDs-PFH and mHIFU effectively suppressed both primary and distant untreated tumors, reducing the tumor volume by 83.3 % (from 657.4 mm³ to 110.0 mm³) and metastatic tumor volume by 76.6 % (from 365.5 mm³ to 85.6 mm³) through enhanced anticancer immune response and a robust abscopal effect. Furthermore, combining NDs-PFH with mHIFU significantly enhanced the efficacy of immune checkpoint inhibitors in liver cancer. When combined with αPD-1 therapy, tumor inhibition improved by 30 % (from 63.6 mm³ to 19.3 mm³) compared to αPD-1 monotherapy. These results highlight the potential of combining mHIFU with a PFH nano-loaded drug delivery system as a promising strategy for advancing antitumor immunotherapy.</div></div><div><h3>Statement of significance</h3><div>Mechanical high-intensity focused ultrasound (mHIFU) can ablate tumors via cavitation effects, however, achieving these effects typically requires an extremely high cavitation threshold. In this study, we utilized widely used perfluorohexane nanodroplets (NDs-PFH) to effectively lower the cavitation threshold. The tumor cell debris generated by the combination of NDs-PFH and mHIFU not only induced immunogenic cells death but also activated antitumor immune responses within the tumor microenvironment. Additionally, our findings demonstrated that this combination elicited a significant abscopal effect and enhanced the efficacy of immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 297-308"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082541","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":"Deep learning assisted prediction of osteogenic capability of orthopedic implant surfaces based on early cell morphology","authors":"Andi Li ,&nbsp;Xinyi Li ,&nbsp;Zhiwen Zhang ,&nbsp;Zihui Huang ,&nbsp;Liqiang He ,&nbsp;Yuhang Yang ,&nbsp;Jiapeng Dong ,&nbsp;Shuting Cai ,&nbsp;Xujie Liu ,&nbsp;Hongli Zhao ,&nbsp;Yan He","doi":"10.1016/j.actbio.2025.01.059","DOIUrl":"10.1016/j.actbio.2025.01.059","url":null,"abstract":"<div><div>The surface modification of titanium (Ti) and its alloys is crucial for improving their osteogenic capability, as their bio-inert nature limits effective osseointegration despite their prevalent use in orthopedic implants. However, these modification methods produce varied surface properties, making it challenging to standardize criteria for assessing the osteogenic capacity of implant surfaces. Additionally, traditional evaluation experiments are time-consuming and inefficient. To overcome these limitations, this study introduced a high-throughput, efficient screening method for assessing the osteogenic capability of implant surfaces based on early cell morphology and deep learning. The Orthopedic Implants-Osteogenic Differentiation Network (OIODNet) was developed using early cell morphology images and corresponding alkaline phosphatase (ALP) activity values from cells cultured on Ti and its alloy surfaces, achieving performance metrics exceeding 0.98 across all six evaluation parameters. Validation through metal-polyphenol network (MPN) coatings and cell experiments demonstrated a strong correlation between OIODNet's predictions and actual ALP activity outcomes, confirming its accuracy in predicting osteogenic potential based on early cell morphology. The Osteogenic Predictor application offers an intuitive tool for predicting the osteogenic capacity of implant surfaces. Overall, this research highlights the potential to accelerate progress at the intersection of artificial intelligence and biomaterials, paving the way for more efficient screening of osteogenic capabilities in orthopedic implants.</div></div><div><h3>Statement of significance</h3><div>By leveraging deep learning, this study introduces the Orthopedic Implants-Osteogenic Differentiation Network (OIODNet), which utilizes early cell morphology data and alkaline phosphatase (ALP) activity values to provide a high-throughput, accurate method for predicting osteogenic capability. With performance metrics exceeding 0.98, OIODNet's accuracy was further validated through experiments involving metal-polyphenol network (MPN) coatings, showing a strong correlation between the model's predictions and experimental outcomes. This research offers a powerful tool for more efficient screening of implant surfaces, marking a transformative step in the integration of artificial intelligence and biomaterials, while opening new avenues for advancing orthopedic implant technologies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 559-568"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082538","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":"Improved tendon repair with optimized chemically modified mRNAs: Combined delivery of Pdgf-BB and IL-1Ra using injectable nanoparticles","authors":"Bettina Faustini ,&nbsp;Thomas Lettner ,&nbsp;Andrea Wagner ,&nbsp;Herbert Tempfer ,&nbsp;Nevra Pelin Cesur ,&nbsp;Christine Lehner ,&nbsp;Chantal Brouwer ,&nbsp;Karin Roelofs ,&nbsp;Olga Mykhailyk ,&nbsp;Christian Plank ,&nbsp;Jaap Rip ,&nbsp;Renate Gehwolf ,&nbsp;Andreas Traweger","doi":"10.1016/j.actbio.2025.02.025","DOIUrl":"10.1016/j.actbio.2025.02.025","url":null,"abstract":"<div><div>Tendon injuries, common in both athletic and non-athletic populations, present significant challenges due to their slow healing and the formation of scar tissue, which impairs function and potentially increases the risk of (re-)rupture. Conventional treatments often yield suboptimal functional and structural repair. This study investigates the potential of mRNA-based therapeutics to enhance tendon healing by targeting 2 distinct pathways via the delivery of chemically modified ARCA-capped mRNAs (cmRNAs) encoding Interleukin-1 receptor antagonist (IL1RA) and Platelet-Derived Growth Factor-BB (PDGF-BB) using injectable nanoparticle (NP) carriers. <em>In vitro</em> experiments demonstrate successful cmRNA delivery and translation, resulting in increased tendon cell proliferation, migration, and anti-inflammatory responses. <em>In vivo,</em> cmRNA treatment notably enhances tendon repair in a rat patellar tendon defect model, by reducing pro-inflammatory cytokines and fibrotic markers while enhancing repair tissue structure. These findings suggest that NP-based cmRNA delivery represents a promising therapeutic strategy for improving tendon healing, offering better outcomes over existing treatments by targeting both inflammatory and regenerative pathways.</div></div><div><h3>Statement of significance</h3><div>In this study, we investigate an mRNA-based therapeutic approach aimed at enhancing tendon healing in a small animal model. Utilizing bioreducible poly(amidoamine)-based polymeric nanoparticles (PAA PNPs) for the delivery of cmRNAs encoding Interleukin-1 receptor antagonist (IL1RA) and Platelet-Derived Growth Factor-BB (PDGF-BB), we demonstrate effective delivery and protein translation <em>in vitro</em> and <em>ex vivo</em>, resulting in enhanced tendon cell proliferation, migration, and robust anti-inflammatory responses. By combining these therapeutic cmRNAs, we show improved tendon repair <em>in vivo</em>, with accelerated tissue regeneration, better collagen fiber organization, and signs of reduced fibrotic scarring. These findings highlight the potential of nanoparticle-mediated cmRNA delivery targeting two distinct pathways to improve tendon healing, offering a promising alternative to current treatments that often yield suboptimal results.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 451-466"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412071","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":"Extracellular matrix ligands modulate the endothelial progenitor cell secretome for enhanced angiogenesis","authors":"Vanessa F.C. Dartora ,&nbsp;Randy Carney ,&nbsp;Aijun Wang ,&nbsp;Peng Qiu ,&nbsp;Alyssa Panitch","doi":"10.1016/j.actbio.2025.02.028","DOIUrl":"10.1016/j.actbio.2025.02.028","url":null,"abstract":"<div><div>Wound healing is a complex physiological process fundamentally dependent on angiogenesis for effective tissue repair. Endothelial progenitor cells (EPCs) have shown significant potential in promoting angiogenesis, primarily through their secretome, rich in proteins and extracellular vesicles (EVs) essential for cell signaling and tissue regeneration. This study investigates the effect of a collagen-bound proteoglycan mimetic (LXW7-DS-SILY or LDS), that binds to the αvβ3 integrin receptor, on the EPC secretome, with a dual focus on the proteomic content and the functional properties of EVs. Utilizing high-resolution two-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS) alongside bioinformatic analysis, we identified significant alterations in protein expression profiles, particularly in angiogenesis and wound healing pathways. The functional impact of these changes was validated through biological assays, where the whole secretome and the EV fraction from EPCs seeded on collagen-bound LDS markedly enhanced vascular network formation, driven by the increase of growth factors and angiogenic regulators such as FGFR1, NRP1, and ANGPT2 within the EV fraction. Gene Ontology (GO) enrichment analysis further highlighted the enrichment of proteins within the EVs driving biological processes, including 'response to wounding' and 'positive regulation of cell motility'. These results underscore that LDS modulates the EPC secretome and significantly enhances its angiogenic potential, offering a promising therapeutic strategy for non-healing and ischemic wounds and suggesting that biomaterials can be modified to control the EV secretome to enhance tissue repair. Functional assays validating the omics data highlight the robustness of LDS as a targeted therapeutic for enhancing angiogenesis and tissue repair in clinical settings. Moreover, the pivotal role of EVs in mediating pro-angiogenic effects offers insights into developing biomaterial therapies that exploit key regulators within the EPC secretome for wound healing.</div></div><div><h3>Statement of significance</h3><div>This manuscript explores how a proteoglycan mimetic that binds to both collagen and the α_vβ₃ integrin receptor affects the proteome component of the secretome from endothelial progenitor cells (EPCs). It presents functional biological data, analytical data, and proteomic analysis of the soluble and extracellular vesical (EV) components of the secratome. The proteomic data maps to the observed enhanced angiogenic potential of the EVs. These results suggest that by controlling the cellular environment and judicially engineering how cells interact with a biomaterial can influence the proteomic composition of EVs to enhance tissue regeneration. This is the foundation of future work aimed at engineering biomaterial cell systems to influence the proteomic component of EVs for therapeutic use.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 240-255"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426845","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":"Subcutaneous liposomal delivery improves monoclonal antibody pharmacokinetics in vivo","authors":"Maryam Karimi ,&nbsp;Arash Aslanabadi ,&nbsp;Ben Atkinson ,&nbsp;Mahsa Hojabri ,&nbsp;Arshi Munawwar ,&nbsp;Roza Zareidoodeji ,&nbsp;Krishanu Ray ,&nbsp;Parham Habibzadeh ,&nbsp;Hanife Nur Karakoc Parlayan ,&nbsp;Anthony DeVico ,&nbsp;Alonso Heredia ,&nbsp;Abdolrahim Abbasi ,&nbsp;Mohammad M. Sajadi","doi":"10.1016/j.actbio.2025.02.035","DOIUrl":"10.1016/j.actbio.2025.02.035","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Background Monoclonal antibodies (mAbs) effectively treat and prevent various diseases, but their clinical application is hindered by issues related to the route of administration and pharmacokinetics (PK). Intravenous (IV) administration is cumbersome, while subcutaneous (SC) administration is hampered by lower bioavailability and potential for immunogenicity. This study evaluated the efficacy of liposomal formulations in enhancing the subcutaneous (SC) delivery and PK of broadly neutralizing antibodies (bNAbs) directed against HIV.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Methods:&lt;/em&gt; mAbs were encapsulated in liposomes with and without PEGylation. The liposomes were characterized for particle size, polydispersity index, zeta potential, and release. Thereafter, mice were injected with free mAbs or liposome-encapsulated mAbs, and PK was evaluated.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Results:&lt;/em&gt; Liposomes exhibited sizes of 85–92 nm with negative surface charges. Encapsulation efficiencies were 61 % for PEGylated and 58 % for non-PEGylated liposomes. Stability testing over 16 weeks revealed that formulations remained stable at 4 °C but showed leakage at 37 C. Cytotoxicity assays confirmed that the liposomal formulations did not affect cell viability or induce apoptosis in HMEC-1 cells. In vivo, PK studies in humanized FcRn mice indicated that the PEGylated formulations generally had higher half-life, Cmax, AUC, and MRT, and lower CL values compared to their non-PEGylated formulations of the same injection type. Both liposomal formulations showed improvements in bioavailability and extended half-life compared to free mAbs administered via SC and IV routes. Compared to the gold standard of IV free mAb injection, SC injection of antibodies encapsulated in PEGylated liposome had up to 80 % higher bioavailability and 45 % extension of half-life. Compared to the SC free mAb injection, the differences were even more pronounced, with liposomal SC injection having up to 113 % higher bioavailability and 81 % extension of half-life.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Conclusion:&lt;/em&gt; Overall, liposomal encapsulation effectively protected SC injected mAbs from degradation, facilitated sustained release, and improved PK profiles, suggesting a promising strategy for enhancing the therapeutic potential of mAbs in conditions that need repeated injections. Future work should further optimize liposomal formulations to increase loading capacity, stability, and release kinetics.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;This study addresses a challenge in the administration of monoclonal antibodies (mAbs). Intravenous administration requires additional resources, including nursing staff, making it time-consuming and costly. Although subcutaneous (SC) administration offers a less expensive and more patient-friendly option, it suffers from lower bioavailability and potentially shorter half-life. In this study, we encapsulated mAbs in liposomal formulations specifically designed to enhance their pharmacokinetics","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 522-535"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451192","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":"Machine learning identifies remodeling patterns in human lung extracellular matrix","authors":"Monica J. Emerson ,&nbsp;Oliver Willacy ,&nbsp;Chris D. Madsen ,&nbsp;Raphael Reuten ,&nbsp;Christian B. Brøchner ,&nbsp;Thomas K. Lund ,&nbsp;Anders B. Dahl ,&nbsp;Thomas H.L. Jensen ,&nbsp;Janine T. Erler ,&nbsp;Alejandro E. Mayorca-Guiliani","doi":"10.1016/j.actbio.2024.12.062","DOIUrl":"10.1016/j.actbio.2024.12.062","url":null,"abstract":"<div><div>Organ function depends on the three-dimensional integrity of the extracellular matrix (ECM). The structure resulting from the location and association of ECM components is a central regulator of cell behavior, but a dearth of matrix-specific analysis keeps it unresolved. Here, we deploy a high-resolution, 3D ECM mapping method and design a machine-learning powered pipeline to detect and characterize ECM architecture during health and disease. We deploy these tools in the human lung, an organ heavily dependent on ECM structure that can host diseases with different histopathologies. We analyzed segments from healthy, emphysema, usual interstitial pneumonia, sarcoidosis, and COVID-19 patients, and produced a remodeling signature per disease and a health/disease probability map from which we inferred the architecture of healthy and diseased ECM. Our methods demonstrate that exaggerated matrix deposition, or fibrosis, is not a single phenomenon, but a series of disease-specific alterations.</div></div><div><h3>Statement of significance</h3><div>The extracellular matrix, or ECM, is the foremost biomaterial. It shapes and supports all tissues while regulating all cells. ECM structure is intricate, yet precise: each organ, at every stage, has a specific ECM structure. During disease, tissues suffer from structural changes that accelerate and perpetuate illness by dysregulating cells. Both healthy and diseased ECM structures are of great biomedical importance, but surprisingly, they have not been mapped in detail. Here, we present a method that combines tissue engineering with machine learning to reveal, map and analyze ECM structures, applied it to pulmonary diseases that kill millions every year. This method can bring objectivity and a higher degree of confidence into the diagnosis of pulmonary disease. In addition the amount of tissue needed for a firm diagnosis may be much smaller than required for manual microscopy evaluation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 94-103"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing titanium dioxide nanotube array stability on dental implants through laser lithography–assisted microline patterning","authors":"Baodi Yin ,&nbsp;Yiwen Dong ,&nbsp;Huan Cheng ,&nbsp;Lifeng Xiong ,&nbsp;Yang Liu ,&nbsp;Yinyan Zhang ,&nbsp;Zhucheng Liu ,&nbsp;Rui Chen ,&nbsp;Peng Gao ,&nbsp;Zijian Zheng ,&nbsp;Mingliang Yu ,&nbsp;Zhennan Deng ,&nbsp;Lei Lu ,&nbsp;Jinsong Liu ,&nbsp;Cuie Wen","doi":"10.1016/j.actbio.2025.01.043","DOIUrl":"10.1016/j.actbio.2025.01.043","url":null,"abstract":"<div><div>Titanium dioxide nanotube arrays (TNTs) generated <em>in situ</em> on the surface of dental implants have been shown to enhance bone integration for load-bearing support while managing load distribution and energy dissipation to prevent bone resorption from overload. However, their inadequate stability limits the clinical use of conventional TNTs. This study introduces an innovative approach to improve the mechanical stability of TNTs while maintaining their bone-integration efficiency. The method involved creating microline patterns on TNTs (<span>L</span>-TNTs), where the TNTs were embedded within grooves for enhanced protection. This was achieved through a combination of laser lithography–assisted microline patterning and anodization. Incorporation of microline patterns significantly increased the mechanical stability of the TNTs. This improvement was evidenced by multiple tests: peeling tests demonstrated the maximum adhesive strength of the <span>L</span>-TNTs increased by at least 50 %; friction-wear tests revealed narrower, shallower abrasion patterns and lower average friction coefficients; and <em>ex vivo</em> screw implant insertion and removal tests showed post-insertion, the nanotube structures in the TNTs peeled, whereas those in the <span>L</span>-TNTs remained intact. The <span>L</span>-TNTs also maintained their efficacy in promoting bone integration both <em>in vitro</em> and <em>in vivo</em>, establishing a robust platform for multifunctional implant investigation and advancing the practical application of TNTs.</div></div><div><h3>Statement of significance</h3><div>This study presents a novel laser lithography–assisted micropatterning and anodization method for creating micro-lined titanium dioxide nanotube arrays (<span>L</span>-TNTs) on dental implants. Compared to conventional TNTs, <span>L</span>-TNTs enhanced adhesive strength and wear resistance while maintaining efficacy in promoting bone integration. This method enhances the mechanical stability of TNTs, facilitating its practical application in multifunctional dental implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 569-581"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070133","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":"Injectable antioxidant hyaluronan/chitosan hydrogel as a platelet-rich plasma and stem cell carrier to promote endometrial regeneration and fertility restoration","authors":"Xiudan Zheng ,&nbsp;Rui Huang ,&nbsp;Lanlan Yin ,&nbsp;Meihua Yao ,&nbsp;Jiaqi Chu ,&nbsp;Fengkai Yang ,&nbsp;Yeying Dong ,&nbsp;Mingyan Zhao ,&nbsp;Tianzhong Ma","doi":"10.1016/j.actbio.2025.01.062","DOIUrl":"10.1016/j.actbio.2025.01.062","url":null,"abstract":"<div><div>Severe damage to the uterine endometrium can lead to thin endometrium and intrauterine adhesions (IUAs), resulting in infertility or complications during pregnancy. Therapies utilizing mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) represent promising strategies for restoring thin endometrium. However, the low homing rate and functionality of transplanted cells, along with the rapid release of PRP growth factors, limit their therapeutic efficacy. In this study, we developed an in-situ formable and redox-responsive hydrogel composed of thiolated hyaluronan (tHA) and thiolated chitosan (tChi) (tHA-tChi) for encapsulating PRP and mouse adipose-derived stem cells (ADSCs). Our results demonstrate that the tHA-tChi hydrogel exhibits appropriate swelling, injectability, self-healing, and antioxidant properties, alongside a sustained release of PRP growth factors. In vitro experiments indicated that the PRP and ADSCs encapsulated within the hydrogel (ADSCs/tHA-tChi/PRP) stimulated angiogenesis in endothelial cells. In a mouse model of thin endometrium, the ADSCs/tHA-tChi/PRP significantly enhanced endometrial regeneration, as evidenced by increased endometrial thickness and reduced fibrosis. This improvement markedly enhanced endometrial receptivity and pregnancy rates in damaged endometria, correlating with increased angiogenesis and endometrial cell proliferation via activation of the VEGF/AKT/BAD pathway, as shown by Western blotting assays. Overall, the combination of antioxidant hydrogel, PRP, and ADSCs demonstrates promising potential for promoting endometrial regeneration and restoring fertility, offering new minimally invasive therapeutic options for endometrial diseases.</div></div><div><h3>Statement of significance</h3><div>This research presents a potent approach to the treatment of thin endometrium, employing an injectable, biodegradable and antioxidant hydrogel comprising thiolated hyaluronic acid (tHA) and thiolated chitosan (tChi). The antioxidant capacity of the hydrogel improves the oxidative microenvironment of the injured uterus, while the hydrogel is designed to release adipose-derived stem cells (ADSCs) and growth factors from platelet-rich plasma (PRP) sustainably, promoting tissue regeneration by enhancing angiogenesis and endometrium cell proliferation. Demonstrated efficacy in a mouse model of thin endometrium indicates its great potential to significantly improve fertility restoration treatments. The administration of antioxidant hydrogel containing ADSCs and PRP represents a promising therapeutic strategy for patients with endometrial disease.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 201-215"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082540","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":"Inflammation-targeted vesicles for co-delivery of methotrexate and TNF-α siRNA to alleviate collagen-induced arthritis","authors":"Liang Yang ,&nbsp;Yongjie Sha ,&nbsp;Yuansong Wei ,&nbsp;Lichen Yin ,&nbsp;Zhiyuan Zhong ,&nbsp;Fenghua Meng","doi":"10.1016/j.actbio.2025.02.005","DOIUrl":"10.1016/j.actbio.2025.02.005","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is an autoimmune disease that has a complex pathogenesis and remains tough to treat. The clinical treatments with e.g. methotrexate (MTX) and TNF-α antibodies show fractional responses and lessen the symptoms only to a certain extent. Here, we developed inflammation-targeted vesicles codelivering methotrexate and TNF-α small interfering RNA (siTNFα) (ITV-MT) for effective ablation of collagen-induced arthritis (CIA) in mice. ITV-MT with tetra-mannose ligand and high loading of MTX (17.1 wt%) and siTNFα (9.0 wt%) displayed a small and uniform size (53 nm) and augmented uptake by inflammatory macrophages leading to superior regulation of macrophage phenotype from M1 to M2 <em>in vitro</em> compared to monotherapies. The intravenous injection of ITV-MT revealed clearly enhanced accretion in the inflamed joints. Interestingly, ITV-MT effectively repolarized M1 macrophages to M2 type, markedly reduced proinflammatory cytokine levels, and significantly attenuated symptoms including joint swelling, arthritis scores and bone damage in the CIA mouse models, by concurrently downregulating both adenosine and TNF-α pathways. This study highlights inflammation-targeted vesicles codelivering methotrexate and TNFα siRNA as a potential strategy to improved RA treatment.</div></div><div><h3>Statement of significance</h3><div>Rheumatoid arthritis (RA) is regarded as an incurable disease, often referred to as an \"incurable cancer\". Current therapies, such as methotrexate (MTX) and anti-TNFα monoclonal antibodies, exhibit limited efficacy and severe adverse effects. The distinct physiochemical properties of MTX and siTNFα hinder their codelivery to RA joints and inflammatory cells. Here, we engineered inflammation-targeted vesicles (ITV-MT) for the codelivery of MTX and siTNFα to enhance therapeutic outcomes. Our findings reveal that ITV-MT significantly improves the drug uptake by macrophages, facilitating repolarization from M1 to M2 phenotypes. In CIA models, ITV-MT effectively downregulated proinflammatory cytokines while upregulating anti-inflammatory cytokines in RA joints, inhibited inflammatory cell infiltration in the synovium and protected against bone erosion. This study highlights that inflammation-targeted co-delivery of small molecular anti-RA agents and RNAi therapeutics may offer a compelling alternative to existing RA treatments, representing a promising strategy for RA treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 338-349"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375111","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":"Biodegradable Magnesium alloy Janus membrane with surface-selective osteoinduction and soft tissue healing properties in guided bone regeneration","authors":"Yujia Han ,&nbsp;Xiaoxia Wang ,&nbsp;Penggong Wei ,&nbsp;Dan Zhang ,&nbsp;Ming Gao ,&nbsp;Zihang Yu ,&nbsp;Qiang Wang ,&nbsp;Lili Tan ,&nbsp;Yulou Tian","doi":"10.1016/j.actbio.2025.02.001","DOIUrl":"10.1016/j.actbio.2025.02.001","url":null,"abstract":"<div><div>Given that the guided bone regeneration (GBR) membrane acts at the interface between the bone and connective tissue, the membrane imposes high demands on the organization of the material. Magnesium (Mg) alloys have emerged as promising candidates for GBR due to their biodegradability and favorable biocompatibility. However, challenges remain in the risk of soft tissue dehiscence and limited osteogenesis for Mg membranes in the clinical application. A dicalcium phosphate dihydrate (CaHPO₄·2H₂O, denoted as DCPD)/MgF₂ Janus membrane was fabricated via chemical conversion and deposition, showcasing suitable degradability, surface-selective osteogenic property and soft tissue healing <em>in vitro and vivo</em>. The DCPD coating was designed to support osteogenesis, while the MgF₂ coating was specifically engineered to facilitate soft tissue healing. Furthermore, the Janus membrane utilized its two-sided properties to show selectivity in adhesion, proliferation, and migration of the MC3T3-E1 and HGFs. <em>In vivo</em> results exhibited its capability to promote bone formation and optimal space maintenance ability. Notably, further RNA-seq analysis demonstrated that different functional cells may respond specifically to two coatings and exert functions. Taken together, these results provide an alternative method for designing surface-selective biomaterials, underlining effective potential applications in bone tissue engineering.</div></div><div><h3>Statement of significance</h3><div>Traditional clinical treatment of bone defects with GBR membranes is frequently constrained to a single superimposed osteogenesis without structural-functional integration. Such a DCPD/MgF₂ coated Janus membrane was fabricated by incorporating chemical deposition and transformation to satisfy optimal osteogenesis and soft tissue healing. Of particular interest, the Janus membrane allowed for chemotactic movement with specific cellular responses to stimuli from different coatings. <em>In vivo</em>, the membrane demonstrated promising effects and showcased space maintenance ability. The design concept exhibits a new avenue to regulate tissue regeneration between different tissue interface, presenting new horizons for the development of GBR membranes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 582-598"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400925","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}