Acta Biomaterialia最新文献

{"title":"Corrigendum to “Sacrificial 3D printing of shrinkable silicone elastomers for enhanced feature resolution in flexible tissue scaffolds” [Acta Biomaterialia, 2020, 117, 261-272]","authors":"Elham Davoodi , Hossein Montazerian , Ali Khademhosseini , Ehsan Toyserkani","doi":"10.1016/j.actbio.2025.04.008","DOIUrl":"10.1016/j.actbio.2025.04.008","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 573-574"},"PeriodicalIF":9.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917748","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":"Corrigendum to “Oxygen-generating microparticles downregulate HIF-1α expression, increase cardiac contractility, and mitigate ischemic injury” [Acta Biomaterialia, 2023, 159, 211-225]","authors":"Kalpana Mandal , Sivakoti Sangabathuni , Reihaneh Haghniaz , Satoru Kawakita , Marvin Mecwan , Aya Nakayama , Xuexiang Zhang , Masoud Edalati , Wei Huang , Ana Lopez Hernandez , Vadim Jucaud , Mehmet R. Dokmeci , Ali Khademhosseini","doi":"10.1016/j.actbio.2025.04.006","DOIUrl":"10.1016/j.actbio.2025.04.006","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 569-570"},"PeriodicalIF":9.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A highly transparent dopamine-copolymerized hydrogel with enhanced ROS-scavenging and tissue-adhesive properties for chronic diabetic wounds","authors":"Haiqi Zhang ,&nbsp;Jinze Wang ,&nbsp;Hongtao Hu ,&nbsp;Lie Ma","doi":"10.1016/j.actbio.2025.04.034","DOIUrl":"10.1016/j.actbio.2025.04.034","url":null,"abstract":"<div><div>Chronic diabetic wounds with complex symptoms represent a major challenge in clinical practice, causing a serious threat to human health and life. Excessive oxidative stress and persistent inflammatory responses are the important reasons for the long-term difficult healing of diabetic wounds. Designing wound dressing materials with intrinsic antioxidant performance, high transparency, adhesiveness, and favorable mechanical properties is of great significance for promoting wound healing, especially in movable parts. Here, a dopamine-copolymerized highly transparent antioxidant hydrogel was developed for the treatment of chronic diabetic wounds. The hydrogel was easily prepared via free radical polymerization using acrylated dopamine monomer (ADA), acrylamide (AM), and phenylboronic acid modified dextran (DP). The dynamic phenylborate ester bonds formed between the catechol of polydopamine and phenylboronic acid effectively mitigated the darkening of the hydrogel color caused by the auto-oxidation of catechol, resulting in the PAM/PDA/DP hydrogel (DP3) with durable transparency. In addition, this hydrogel had good adhesiveness and mechanical properties, as well as desirable reactive oxygen species (ROS)-scavenging performance. Furthermore, <em>in vivo</em> results demonstrated that DP3 hydrogel can stimulate the polarization of macrophages toward anti-inflammatory M2 phenotype, increase the secretion of anti-inflammatory factors, so as to smooth the transition of wound healing from the inflammatory phase to the proliferative phase, and accelerate the repair of diabetic wounds by promoting angiogenesis and collagen deposition. Therefore, the DP3 hydrogel holds great potential for remolding the tissue regeneration microenvironment and serving as a promising dressing for chronic diabetic wounds.</div></div><div><h3>Statement of significance</h3><div>Polydopamine (PDA)-based hydrogels have been widely explored. However, existing PDA-based hydrogels suffer from low content of catechol groups and inferior transparency, and are prone to oxidation darkening during storage. In this study, a dopamine-copolymerized hydrogel with high catechol content was developed. The catechol groups are partially protected by phenylboronic acid-modified dextran, resulting in durable transparency and good adhesiveness of the hydrogel. The hydrogel exhibits desirable antioxidant performance and can effectively promote chronic diabetic wound healing by relieving oxidative stress and regulating immune function. This highly transparent hydrogel with intrinsic antioxidation and self-adhesiveness properties represents a potential and effective strategy for chronic wound management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 161-173"},"PeriodicalIF":9.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A therapeutic strategy integrating ultrasound-guided microwave ablation with nanocomposite hydrogels to enhance autophagy and suppress tumor growth in hepatocellular carcinoma","authors":"Yi Duan ,&nbsp;Li Ding ,&nbsp;Xianwei Meng ,&nbsp;Jiangtao Lin ,&nbsp;Hao Fu ,&nbsp;Yan Zhu ,&nbsp;Yijie Qiu ,&nbsp;Jiaying Cao ,&nbsp;Jian Hu ,&nbsp;Yi Dong ,&nbsp;Yourong Duan ,&nbsp;Jianhua Chen","doi":"10.1016/j.actbio.2025.04.032","DOIUrl":"10.1016/j.actbio.2025.04.032","url":null,"abstract":"<div><div>Microwave ablation (MWA) is widely recognized as an effective radical therapy for hepatocellular carcinoma (HCC). However, local ablation often results in a high risk of tumor recurrence. To address this challenge, we developed an effective anticancer drug delivery system comprising arsenic trioxide (As₂O₃)-loaded polyethylene glycol-dipalmitoylphosphatidylethanolamine (mPEG-DPPE) calcium phosphate nanoparticles (As₂O₃_<img>NPs) encapsulated within an injectable thermoresponsive hydrogel (ANPs-Gel). This study evaluated the therapeutic efficacy of MWA combined with ANPs-Gel in a rabbit hepatic VX2 tumor model. Ultrasound (US) and contrast-enhanced ultrasound (CEUS) were employed to assess tumor response and angiogenesis following treatment. The results demonstrated that MWA combined with ANPs-Gel significantly enhanced antitumor efficacy compared to other treatments, effectively inhibiting tumor growth and angiogenesis. Mechanistically, the therapeutic effects were associated with autophagy induced by MWA+ANPs-Gel, which played a critical role in promoting tumor cell death and suppressing epithelial-mesenchymal transition (EMT) both <em>in vitro</em> and <em>in vivo. In vivo</em> experiments further highlighted that the injectable thermoresponsive hydrogel system not only prolonged drug retention at the tumor site but also enhanced therapeutic efficacy by reducing EMT and preventing tumor recurrence. These findings suggest that MWA combined with ANPs-Gel provides a promising strategy for improving treatment outcomes in HCC through ultrasound-guided chemotherapy and targeted autophagy modulation.</div></div><div><h3>Statement of significance</h3><div>This study introduces a potent therapeutic strategy that integrates ultrasound-guided microwave ablation (MWA) with a nanocomposite hydrogel to enhance autophagy and suppress tumor growth in hepatocellular carcinoma, as demonstrated in the rabbit VX2 hepatic tumor model. By combining advanced ultrasound guidance with a sophisticated nanomaterial platform, this approach significantly improves the efficacy of localized cancer therapy. Unlike conventional treatments, it not only ablates tumor cells but also regulates key cellular processes, such as autophagy, to amplify therapeutic outcomes. This work repurposes arsenic trioxide (Arsenic Trioxide) within a nanocomposite hydrogel delivery system and provides a detailed exploration of its therapeutic mechanisms when combined with MWA therapy. These findings pave the way for advanced clinical strategies in liver cancer management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 413-427"},"PeriodicalIF":9.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917732","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":"Elastic strain and strength–elongation performance of medium-entropy Zr–Nb–Ti–O alloys for bone implants","authors":"Zhaolin Hua ,&nbsp;Dechuang Zhang ,&nbsp;Lin Guo ,&nbsp;Sihan Lin ,&nbsp;Xiaokai Zhang ,&nbsp;Yuncang Li ,&nbsp;Cuie Wen","doi":"10.1016/j.actbio.2025.04.029","DOIUrl":"10.1016/j.actbio.2025.04.029","url":null,"abstract":"<div><div>Beta-type Zr–Nb–Ti (ZNT) medium-entropy alloys (MEAs) are receiving increasing research interest as orthopedic implants due to their appropriate mechanical properties, corrosion resistance, and biocompatibility. However, improvements in their elastic admissible strain, strength, and ductility are still required to ensure their high performance in clinical applications. In this study, a series of (ZrNbTi)_100–xO_x (<em>x</em> = 0, 0.5, 1.0, and 1.5; denoted ZNTO₀, ZNTO_0.5, ZNTO_1.0, and ZNTO_1.5) MEAs were fabricated by arc melting followed by cold-rolling and annealing. Their microstructures, mechanical properties, wear and corrosion resistance, and biocompatibility were systematically studied. The addition of oxygen could simultaneously enhance strength and ductility owing to interstitial solid-solution strengthening and strain-hardening. ZNTO_0.5, ZNTO_1.0, and ZNTO_1.5 showed significantly improved elastic admissible strain and strength-elongation product compared to ZNTO₀; in particular, ZNTO_1.5 exhibited the best combination of mechanical properties with an admissible strain of ∼1.5 %, an ultimate strength of ∼1150 MPa, and an elongation of ∼22 %. The wear and corrosion resistance of the ZNTO_x MEAs increased with increasing oxygen content. The ZNTO_x MEAs showed better corrosion resistance than those of Ti–6Al–4V and Co–Cr–Mo alloys due to formation of surface passivation film composed of ZrO₂, Nb₂O₅, and TiO₂ oxides. The ZNTO_x MEAs also showed cell viability of &gt;97 % toward MG-63 cells. Overall, the ZNTO_1.5 MEA has significant potential as an orthopedic implant material due to its comprehensive mechanical properties, high wear and corrosion resistance, and adequate biocompatibility.</div></div><div><h3>Statement of significance</h3><div>This work reports on ZNTO_x (<em>x</em> = 0, 0.5, 1.0, and 1.5) medium-entropy alloys (MEAs) with a comprehensive combination of biomechanical, corrosion, and biocompatibility properties. The addition of O to ZNT MEAs can significantly improve their elastic admissible strain, strength-elongation product, and wear and corrosion resistance. The ZNTO_x MEAs showed better corrosion resistance in Hanks’ solution than Ti–6Al–4V and Co–Cr–Mo alloys and cell viability of &gt;97 % toward MG-63 cells. The results demonstrate that the ZNTO_1.5 MEA has significant potential as an orthopedic implant material due to its best combination of elastic admissible strain and strength-elongation product, effective wear and corrosion resistance, and adequate biocompatibility.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 530-545"},"PeriodicalIF":9.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917745","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":"An injectable in situ gel formed by ropivacaine with small lipid molecules to achieve long-term postoperative analgesia","authors":"YiQing Shen ,&nbsp;Xin Tan ,&nbsp;Lin Zhou ,&nbsp;ZiHan Sun ,&nbsp;Min Han ,&nbsp;Min liang ,&nbsp;DongHang Xu","doi":"10.1016/j.actbio.2025.04.033","DOIUrl":"10.1016/j.actbio.2025.04.033","url":null,"abstract":"<div><div>Although local anesthetics (LA) are non-addictive and effective in managing postoperative pain, their short-term effects limit their clinical utility. In this study, we constructed an <em>in situ</em> gel injection formulation with stearic acid-ropivacaine hydrophobic ion-pair (HIP) and glycerol monoglyceride (SA-ROP-GMS) for multiday postoperative pain management. As an <em>in situ</em> gel, SA-ROP-GMS avoids the burst release effect common to water-soluble small molecule drugs in liposomes and hydrogels. Meanwhile, the hydrophobic ion-pair formed by ropivacaine and stearic acid contributes to the gel's stabilization and slow-release properties. <em>In vivo</em> evaluation of mouse models of pain demonstrated that the formulation provided multiday analgesia. And the absence of systemic toxicity of SA-ROP-GMS was verified by histological and blood biochemical studies. This study demonstrated the safety and efficacy of an injectable ropivacaine formulation based on <em>in situ</em> gel. The materials used in SA-ROP-GMS are safe and easy to obtain, and the preparation process is simple and fast, providing a convenient and effective strategy for the development of single-dose long-acting local anesthetic products, which is of great significance for postoperative pain management.</div></div><div><h3>Statement of Significance</h3><div>More than 80% of patients experience severe postoperative pain, and poor pain control reduces recovery satisfaction while increasing the risk of chronic pain. In this study, we constructed an injectable <em>in situ</em> gel using all-small-molecule excipients for slow-release drug delivery for the first time. We designed a method to form a lipid drug coupling between ropivacaine and stearic acid (SA-ROP HIP), which was then combined with glyceryl monostearate (SA-ROP-GMS). SA-ROP-GMS maintained analgesia for nearly 10 days in a single dose, significantly improving ease of administration and patient compliance. In addition, the auxiliary ingredients used in this study are biocompatible and inexpensive. This formulation follows the trend of regional anesthesia and provides a new solution for postoperative pain management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 151-160"},"PeriodicalIF":9.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916233","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":"Promotion of bone defect repairs using multiscale 3D printed silk porous hydrogel scaffolds","authors":"Qiucen Liu ,&nbsp;Li Chen ,&nbsp;Hongxiang Liu ,&nbsp;Tao Wang ,&nbsp;Gang Li ,&nbsp;Zhaozhu Zheng ,&nbsp;Xiaoqin Wang ,&nbsp;David L. Kaplan","doi":"10.1016/j.actbio.2025.04.027","DOIUrl":"10.1016/j.actbio.2025.04.027","url":null,"abstract":"<div><div>Porosity plays a critical role in influencing the biological properties and performance of materials and devices. This study introduces hydrocolloid inks by incorporating porogens into silk fibroin (silk) protein solutions to generate porous hydrogel scaffolds. These inks exhibit robust printability, enabling the fabrication of complex geometries with hierarchical porosity, ranging from microscale porogen-templated pores (40 to 200 μm, with over 50 % ≥100 μm) to macroscale features determined by the 3D printing process (≥200 μm). Compatibility studies using human bone marrow mesenchymal stem cells (hMSCs) and murine embryonic osteoblast precursor cells (MC3T3-E1) demonstrate cell adhesion, infiltration, and proliferation both on the surface and within these hydrogels. Subcutaneous implantation in rats confirmed biocompatibility and the ability to support endogenous cell migration and proliferation by the hydrogels. In a rat femoral defect model, the microscale biomimetic structures significantly improved bone repair, outperforming control groups, including small pore-sized silk hydrogels (∼21.39 μm) and other 3D-printed constructs with a thickening agent (∼20.78 μm). These innovative multiscale silk 3D biomimetic scaffolds present a promising approach for effective bone defect repair for future clinical applications.</div></div><div><h3>Statement of significance</h3><div>This study presents a transformative approach to bone defect repair through the development of 3D-printed silk hydrogel scaffolds with multiscale porosity. By incorporating dextran gel particles as sacrificial porogens, the silk scaffolds achieve hierarchical pore structures optimized for cell adhesion, proliferation, and migration. <em>In vitro</em> and <em>in vivo</em> results demonstrate that these scaffolds support robust cellular activity and significantly enhance bone regeneration compared to conventional designs, providing a scalable, biocompatible solution. The integration of silk's superior biological properties with advanced 3D printing methodologies underscores its potential to set new benchmarks in bone tissue engineering and regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 24-36"},"PeriodicalIF":9.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916108","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":"Free carrier-enhanced Bi/Bi2S3 nanoparticles enable precise OCT catheter-guided interventional photothermal therapy for colorectal cancer","authors":"Xiaoyu Huang ,&nbsp;Fan Yang ,&nbsp;Beibei Gao ,&nbsp;Wei Ge ,&nbsp;Lu Gao ,&nbsp;Jigang Wu ,&nbsp;Shengxian Tu ,&nbsp;Fu Wang","doi":"10.1016/j.actbio.2025.04.018","DOIUrl":"10.1016/j.actbio.2025.04.018","url":null,"abstract":"<div><div>Current clinical colorectal cancer treatments usually possess unsatisfactory effects, mainly because of unavoidable surgical trauma and multidrug resistance. Precise and minimally invasive theragnostic technology has advanced through miniaturized catheter intervention with imaging-guided treatment methods; however, previously reported approaches cannot simultaneously perform <em>in situ</em> real-time imaging and therapy. We proposed a strategy of 0.9 mm catheter-based optical coherence tomography imaging-guided interventional photothermal therapy at 1310 nm for orthotopic colorectal cancer. Specifically, folate-modified Bi/Bi₂S₃ nanoparticles showed intense scattering signals and local hyperpyrexia under 1310 nm laser irradiation <em>in vitro</em> and <em>in vivo</em> due to the localized surface plasmon resonance effect, enabling imaging-guided precise tumor treatment. Histopathological and blood biochemistry analyses confirmed the high biosafety and negligible long-term toxicity of Bi/Bi₂S₃ nanoparticles. This new method offers a feasible methodology for catheter-based precise interventional photon theragnostics.</div></div><div><h3>Statement of significance</h3><div>Emerging minimally invasive techniques have been explored for the treatment of colorectal cancer (CRC); however, these reported approaches cannot reach the requirement of precise orthotopic cancer treatment due to the lack of <em>in situ</em> real-time imaging guidance. This study proposes a 0.9 mm catheter-based OCT imaging-guided interventional photothermal therapy (IPTT) strategy at 1310 nm for treating orthotopic CRC. Folate-modified plasmonic Bi/Bi₂S₃ nanoparticles enable real-time imaging-guided IPTT by providing strong scattering signals and local hyperthermia. This approach allows simultaneous transmission of imaging and therapy light in the same optical fiber, offering a promising method for precise CRC theragnostics and addressing the gap of <em>in situ</em> real-time imaging during IPTT.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 401-412"},"PeriodicalIF":9.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917822","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":"Dual-responsive magnetic vortex nanorings co-deliver lenvatinib and localized heat for synergistic activation of antitumor immunity","authors":"Zirui Ye ,&nbsp;Bin Yan ,&nbsp;Hugang Li ,&nbsp;Qianqian Tang ,&nbsp;Kexin Yuan ,&nbsp;Jingjing Hou ,&nbsp;Lexuan Xu ,&nbsp;Jianlan Yuan ,&nbsp;Siyao Wang ,&nbsp;Wangbo Jiao ,&nbsp;Haiming Fan ,&nbsp;Yi Lyu ,&nbsp;Bo Wang ,&nbsp;Xiaoli Liu","doi":"10.1016/j.actbio.2025.04.014","DOIUrl":"10.1016/j.actbio.2025.04.014","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) presents significant treatment challenges, primarily due to its ability to suppress immune responses. Lenvatinib (LT), approved as a first-line therapy for HCC, modulates the immune microenvironment by reducing PD-L1 expression and decreasing the infiltration of regulatory T cells (T_regs) within the tumor. However, the low immunogenicity of HCC and high toxicity of LT often undermine its effectiveness. To address these challenges, polydopamine (PDA)-coated ferrimagnetic vortex-domain iron oxide nanorings (FVIO@PDA) were engineered to respond to both acidic conditions and magnetic fields, facilitating the simultaneous delivery of the drug (LT) and a physio-therapeutic heat modality. The dual-responsive nature of FVIO@PDA ensures a controlled and synergistic release of LT, activated by acidic tumor microenvironments and the heat produced by an alternating magnetic field (AMF). In a subcutaneous Hepa1–6 HCC model, LT-loaded FVIO@PDA-PEG (denoted as LT-loaded FPP)-mediated magnetic hyperthermia significantly increased the levels of cytotoxic T lymphocytes, showing an approximate 3.86-fold increase compared to the control groups. This combination of LT and magnetic hyperthermia also reduced Treg populations to 1.4 %, synergistically triggering a robust antitumor immune response. Additionally, it altered cytokine profiles, reducing the secretion of the immunosuppressive cytokine IL-10 to 0.41 times that of control levels, while increasing the secretion of pro-inflammatory cytokines IFN-γ and TNF-α by 3.25 and 4.34 times, respectively. Furthermore, LT-loaded FPP-mediated magnetic hyperthermia exhibits superior anti-tumor activity compared to either treatment alone. These results highlight the promise of combining LT with FPP-mediated immunogenic magnetic hyperthermia as a potent therapeutic strategy for HCC, offering a more effective approach to modulate the immune environment and enhance antitumor efficacy.</div></div><div><h3>Statement of significance</h3><div>Lenvatinib (LT) is a selective multi-targeted tyrosine kinase inhibitor used for patients with unresectable HCC who have not previously undergone systemic therapy. LT's immunomodulatory effects alone are often insufficient to induce an effective immune response, and treatment outcomes continue to be unsatisfactory. We developed FVIO@PDA for the delivery of LT and localized heat. FVIO@PDA allowed for controlled release of LT, triggered by the acidic tumor microenvironment and the heat generated under an AMF. LT combined with magnetic hyperthermia increased CTLs, reduced T_regs, decreased immunosuppressive cytokines, and elevated pro-inflammatory ones, collectively initiating a strong antitumor immune response. LT combined with magnetic hyperthermia showed superior antitumor effect compared to either treatment alone.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 389-400"},"PeriodicalIF":9.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917821","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":"Nanodrug-loaded microneedles promote scar-reduced repair after spinal cord injury by re-establishing microglial homeostasis","authors":"Wenbo He ,&nbsp;Li Zhang ,&nbsp;Datong Zheng ,&nbsp;Liansha Tang ,&nbsp;Yi Zhang ,&nbsp;Min Peng ,&nbsp;Zhigang Wang ,&nbsp;Chongxi Xu ,&nbsp;Zhouhaoran Chen ,&nbsp;Yi Liu ,&nbsp;Jianguo Xu ,&nbsp;Maling Gou ,&nbsp;Yu Hu","doi":"10.1016/j.actbio.2025.04.026","DOIUrl":"10.1016/j.actbio.2025.04.026","url":null,"abstract":"<div><div>The persistent activation of microglia is a key factor contributing to neuronal damage and inhibiting the repair of spinal cord injury (SCI). Re-establishing local microglial homeostasis during the early stages of injury presents a novel approach for scar-reduced repair after SCI. Nitroxoline (Nit) can reinstate microglial homeostasis after their activation in vitro. However, the poor water solubility and low blood-spinal cord barrier permeability limit the potential application of Nit in SCI. Here, a dual drug-delivering system (Nit-MNs) composed of self-assembled nano-micelles and gelatin methacryloyl microneedles was further designed. The nano-micelles resolved the solubility issues of Nit while facilitating sustained release. The Nit-MNs enabled continuous drug delivery into the intrathecal space through the micro-perforations created in the dura mater. In the rat spinal cord contusion model, the implantation of Nit-MNs reduced scar formation, promoted neural regeneration, and subsequently restored neurological function. Further studies demonstrated that Nit-MNs promoted the re-establishment of microglial homeostasis, probably through inhibiting the expression of cathepsin B. Therefore, our functional Nit delivery system provides a promising drug-based delivery strategy for SCI treatment.</div></div><div><h3>Statement of significance</h3><div>Small molecule drugs have demonstrated therapeutic effects by targeting various pathological processes of SCI, but the efficacy and precise delivery often limit their broader application. In this study, we identified a small molecule drug (Nit) as a potential candidate for promoting SCI repair by facilitating the re-establishment of microglial homeostasis. Additionally, we developed a dual drug-delivering system comprising self-assembled nano-micelles and gelatin methacryloyl microneedles. This system achieved transdural delivery and dual sustained release of Nit at the precise injury site, effectively promoting the scar-reduced repair after SCI. Our research provides insights for the development of novel delivery systems that match the therapeutic characteristics of small molecule drugs for SCI.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 440-451"},"PeriodicalIF":9.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917734","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}