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Regenerative Biomaterials · 2026 · IF 8.7

Synergistic self-assembly and crosslinking yield a durable, bioactive, and injectable recombinant collagen implant for photoaging therapy

Wei Nannan,Zhang Yuchen,Tian Xinyu,Yao Linyan,Xiao Jianxi

Sustained ultraviolet (UV) irradiation upregulates matrix metalloproteinases (MMPs) activity, exacerbates collagen degradation, and triggers inflammatory signaling, leading to extracellular matrix (ECM) disorganization and skin photoaging. While animal-derived collagens are widely used in clinical applications, their immunogenicity and batch variability limit safety and consistency. Recombinant collagen provides a safer and more controllable alternative. However, poor fibrillogenesis, limited structural stability, and rapid enzymatic degradation hinder long-term performance. Here, we developed an injectable recombinant collagen nanofiber implant (B-SARCI) through the synergistic integration of molecular self-assembly and mild 1,4-butanediol diglycidyl ether (BDDE) crosslinking. This dual strategy preserves excellent injectability while simultaneously enhancing thermal stability, and enzymatic resistance. B-SARCI improved fibroblast attachment and proliferation, promoted migration, and facilitated differentiation in vitro. In a murine UV-induced photoaging model, B-SARCI restored dermal density, enhanced barrier function, and reduced transepidermal water loss (TEWL). Transcriptomic and histological analyses revealed upregulation of Col1α1 and Col3α1, suppression of MMP2, MMP3, and MMP9, and modulation of the JAK-STAT pathway via SOCS3 induction and IL-6 downregulation. Together, these findings demonstrate that B-SARCI re-establishes ECM homeostasis and attenuates inflammation, representing a durable, bioactive, and clinically translatable recombinant collagen implant for photoaged skin repair.

CAS / MDL: 2425-79-8 25389-94-0
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2026 · IF 8.7

Paeoniflorin-loaded MBG Nanogel Alleviates Oxidative Microenvironment and Reinforces Subchondral Bone Regeneration for Osteoarthritis Treatment

Wu Zugui,Huang Xiuhong,Li Jiao,Zheng Gaoquan,Peng Feng,Dong Wei,Zhu Yue,Zhang Yu,Yuan Rong,Wu Zhiwei,Guo Ying,Xiao Jin,Wan Biaolin

Osteoarthritis (OA) involves synergistic pathological changes in both cartilage degradation and subchondral bone remodeling due to oxidative stress, yet current therapies typically target these processes separately. To address this limitation, we developed a dual-functional nanogel (MBG@Pae@HA) by conjugating hyaluronic acid (HA) and paeoniflorin (Pae) to mesoporous bioactive glass nanoparticles via amide bonding and non-covalent interactions, respectively. Leveraging the inherent hydrophilicity of HA, MBG@Pae@HA spontaneously forms nanogels and shows enhanced adhesion force which ensure extended Pae and bioactive ions release in the OA microenvironment. MBG@Pae@HA exhibits potent reactive oxygen species (ROS)-scavenging capacity, contributing to the homeostatic balance between cartilage matrix anabolism and catabolism. Transcriptomic analysis revealed that MBG@Pae@HA treatment reactivates chondrocyte function through activating the cAMP/PKA/CREB antioxidant pathway. Furthermore, with controlled release of Pae and bioactive components (including Ca ions, Si ions, and PO43-⁠) it significantly promotes osteogenesis of bone stem cells. Medial meniscotibial ligament (DMM) model demonstrated the dual therapeutic efficacy of MBG@Pae@HA nanogel with histological and micro-CT analyses confirming concurrent protection against cartilage degradation and enhancement of subchondral bone regeneration. By simultaneously addressing both major pathological features of OA through microenvironment remodeling and prolonged drug delivery, this HA-functionalized and Pae-loaded nanogel represents a significant advance in OA treatment strategies, offering a comprehensive approach to halt disease progression and promote joint repair.

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Regenerative Biomaterials · 2026 · IF 8.7

Photothermal and cascade ROS generative multilayer as intraocular lens surface coating for effective posterior capsular opacification inhibition

Zhang Renjie,Jia Qingqing,Wang Jiahao,Li Wei,Chen Jiang,Hong Wenxin,Huang Huiying,Lin Quankui

Cataract is the leading cause for blindness. While the intraocular lens (IOL) implantation is the only effective treatment in cataract surgery. Posterior capsule opacification (PCO) is the most frequent complication after cataract surgery, mainly resulting from the proliferation and migration of residual human lens epithelial cells (HLECs) within the capsular bag. While surface modification of IOL has helped slow its progression, long-term effectiveness and biocompatibility remain major challenges. Supraphysiological concentration of reactive oxygen species (ROS) induced by natural enzyme stimulation can effectively inhibit proliferation and migration of HLECs, but the effect is limited by enzyme instability. Gold nanoparticles (AuNPs), a promising candidate with enzyme-mimicking activity and desirable photothermal effects, can promote ROS generation and enhance cell apoptosis. To prevent AuNPs aggregation, Fe3+ containing MIL metal-organic frameworks (MOFs) were used as a supporting framework to obtain AuNPs@MIL, which was then modified onto IOL material via electrostatic layer by layer (LbL) self-assembly technique to improve stability and increase immobilization efficiency. The cascade catalytic process, initiated by AuNPs@MIL, can catalyze glucose and oxygen oxidation to produce gluconic acid and hydrogen peroxide. In the formed acidic environment, AuNPs, along with Fe3+ from MIL, convert H2O2 into ·OH via oxidase-like and Fenton-type reactions, which will accelerate cell apoptosis. Additionally, NIR-induced photothermal therapy (PTT) of AuNPs further eliminates abnormally proliferating cells. In vitro and in vivo studies demonstrate that AuNPs@MIL modified IOL offers effective PCO prevention effect, good biocompatibility and excellent optical properties, presenting a viable solution for long-term, efficient PCO prevention.

✓ 已验证 DOI 高影响因子
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Regenerative Biomaterials · 2026 · IF 8.7

Biomimetic lung-targeting vehicle coupled with cryo-shocked leukocyte and inflammation-anchored liposome for drug delivery and anti-inflammation in treatment of acute pneumonia

Zhang Jinniu,Zeng Yixing,Huang Yun,Zhu Chunyun,Shen Wenhao,Miao Yingjing,Feng Nianping,Ci Tianyuan

Acute pneumonia is a severe pulmonary inflammation and it is critical to promptly suppress the dysregulated inflammatory responses to prevent mortality. Glucocorticoids are the first-line therapeutic drugs but with poor tissue selectivity and dose-dependent adverse effects. In this work, cryo-leukocyte, an autologous cell-derived immunosuppressor, was created leveraging the cryo-shocking technology by the quick shock of normal leukocytes with liquid nitrogen. After coupling with aICAM-1 functionalized liposomes, this micro/nano composite system could achieve efficient and prompt inflammation alleviation in acute pneumonia. The engineered cryo-leukocytes were of well biocompatibility after evaluation of blood toxicity, tissue toxicity, acute toxicity and long-term biosafety for over six months, etc. Cryo-leukocytes preserved similar cellular receptors as normal leukocytes, capable of recognizing and binding inflammatory cytokines but without activation of immune cascade, thus exhibiting obvious anti-inflammation efficacy by acting as “mixed cytokines antibodies”. The immunosuppression efficacy of cryo-leukocytes was also superior than that of its sub-group cells of cryo-neutrophil, cryo-monocyte and cryo-lymphocyte, due to relative wide protein expressions that are related to the immune responses. Besides, cryo-leukocytes coupled with aICAM-1 functionalized liposome exhibited obvious anchoring effect in inflammation sites by the interaction of ICAM-1 antibody and ICAM-1 molecules that were over-expressed on inflammatory pulmonary endothelial cells, thus served as superior drug lung-targeting vehicle to maximally enhance the accumulation of traditional Chinese and Western medicines in the lungs. 68.1% of drug signals could be observed in lung tissues compared with other major organs after intravenous injection, significantly higher than that of micro-sized drug-loaded cryo-leukocyte (18.6%) and nano-sized drug-loaded aICAM-1-liposome (12.2%). In a lipopolysaccharide-induced acute pneumonia mice model, the drug-loaded cryo-leukocyte achieved superior anti-inflammation efficacy with 87.5% survival of mice after treatment.

✓ 已验证 DOI 高影响因子
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Regenerative Biomaterials · 2026 · IF 8.7

Functionalized Magnetic Hydrogel Encapsulation of Human Dental Follicle Stem Cells under a Static Magnetic Field Enhances Multi-site Bone Regeneration

Deng Peishen,Zheng Manhong,Du Bing,Liu Changyu,Cheng Renyi,Liu Chaofeng,Wang Fang,Dong Hangyu,Shan Yan,Xu Yanhua

Repairing large-scale craniomaxillofacial bone defects is hindered by a limited availability of stem-cell sources and a low osteogenic efficiency. To address these challenges, Fe3O4 nanoparticles were modified with methacrylic anhydride (MAA) which helped to introduce photopolymerizable methacryloyl groups, resulting in MAA-Fe3O4 nanoparticles that exhibit excellent magnetic properties and colloidal stability. These nanoparticles were incorporated into gelatin methacryloyl (GelMA) and covalently crosslinked to form an injectable, photocurable GelMA-Fe3O4 magnetic composite hydrogel. This hydrogel provides a three-dimensional (3D) culture microenvironment for human dental follicle stem cells (hDFSCs), and upon encapsulation, osteogenesis was significantly enhanced under a 100 mT static magnetic field (SMF). In vitro, GelMA-Fe3O4 hydrogels demonstrated increased porosity and improved mechanical properties, thereby significantly promoting hDFSCs proliferation, adhesion, and spreading. Additionally, under SMF exposure, the expression of osteogenesis-related genes and proteins, including ALP, Runx2, Col-I, and OPN, was significantly upregulated. In a rat calvarial defect model, bone mineralization centers with multi-site distribution were observed in the GelMA-Fe3O4 + SMF group as early as 4 weeks postoperatively, leading to high-quality defect repair. The limitations of traditional 'peripheral-to-center’ unidirectional repair were overcome by this model of synchronous multi-site osteogenesis, maximizing bone regeneration with a minimal number of stem cells and providing an efficient, controllable tissue-engineering strategy for the clinical treatment of craniomaxillofacial bone defects.

✓ 已验证 产品关联 DOI 高影响因子
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Regenerative Biomaterials · 2026 · IF 8.7

Integrated platform for EV separation and controlled release based on gelatin microspheres for diabetic wound treatment

Zhang Yiqing,Huang Qilin,Meng Hao,Chen Junli,Hao Yaying,Liu Xi,Xu Yangmengyuan,Ma Liqian,Xu Zhan,Ma Kui,Hu Wenzhi,Pan Xiaohua,Fu Xiaobing,Zhang Cuiping

Diabetic wounds exhibit impaired healing owing to multiple pathological factors and current treatment options remain limited, underscoring the urgent need for novel therapeutic strategies. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are emerging as promising candidates for wound healing. However, the process from isolation to application of EVs is complex and time-consuming, which probably influences the activity and the therapeutic effects of EVs. To address these issues, we created the integrated platform for EV separation and controlled release. Gelatin microspheres (GMS) were prepared and functionalized with the variable domain of heavy-chain-only antibodies (GMS-VHH). GMS-VHH enabled the efficient capture of CD9-positive EVs in the culture supernatant of MSCs, forming EVs-loaded gelatin microspheres (GMS@EVs). The characterization of EVs demonstrated that the GMS-VHH isolation method outperformed traditional ultracentrifugation in terms of EV structural integrity. GMS@EVs exhibited excellent biocompatibility and promoted the proliferation of epidermal keratinocytes in vitro. In addition, the controlled release and the therapeutic efficacy of GMS@EVs were also observed in the treatment of diabetic wounds. Transcriptomic analysis illustrated that the wound healing-related genes were significantly upregulated and the pro-inflammatory genes as well as the wound healing-impaired genes were downregulated. Collectively, this study introduces a “ready-to-use” platform for EV isolation and controlled release, providing a promising strategy for diabetic wound repair.

✓ 已验证 DOI 高影响因子
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Regenerative Biomaterials · 2026 · IF 8.7

The 3D printed biphasic scaffolds incorporating epimedin C promotes osteochondral regeneration in osteoarthritis rats

Meng Xiangbo,Chang Le,Wang Huajun,Li Jiming,Huang Cuishan,Jiang Yuxi,Zhang Yuting,Cao Huijuan,Li Ling,Yang Wenyao,Xu Jiake,Qin Ling,Zheng Xiaofei,Cheng Wenxiang,Wang Xinluan

The regeneration of osteochondral defect in osteoarthritis (OA-OCD) remains a significant clinical challenge, frequently accompanied by synovial inflammation and persistent joint pain. Tissue engineering scaffolds show promising application prospects; however, due to their lack of bioactive molecules, they often fail to effectively regulate extracellular matrix remodeling and inflammatory responses, resulting in poor repair outcomes. In our previous study, we identified epimedin C (Epi C) as one of the most bioactive compounds from Xianlinggubao (XLGB) through 3D human osteoarthritic chondrocyte pellet cultures, demonstrating significant anti-inflammatory and anabolic effects. In this study, we developed a novel biphasic scaffold incorporating Epi C to enhance osteochondral regeneration in an OA-like microenvironment. The biphasic scaffold consists of a cartilage phase [PLGA (50:50)] and a subchondral bone phase [PLGA (75:25)/β-TCP], both with biomimetic pore sizes, porosity and mechanical properties, while the incorporation of Epi C did not compromise the scaffold’s structural integrity. In vitro degradation experiments revealed that the cartilage phase degraded rapidly, facilitating the prompt release of Epi C, while the subchondral bone phase exhibited slower degradation, allowing for sustained drug release over an extended duration. In a rat OA-OCD model, PTP@Epi C scaffold significantly promoted subchondral bone regeneration compared to the OA-OCD group and PTP group. Additionally, the PTP@Epi C scaffold effectively inhibited the expression of TNF-α in the synovial tissue, thereby alleviating synovitis. Transcriptomic analysis and in vitro experiments demonstrate that Epi C downregulates NLRP3 mRNA expression by inhibiting the phosphorylation of IκBα and p65, thereby preventing p65 nuclear translocation and reducing NF-κB transcriptional activity. This ultimately suppresses NLRP3 mRNA levels and decreases downstream IL-1β secretion. In summary, the PTP@Epi C scaffold significantly enhances the osteochondral regeneration and improves the synovial microenvironment through a layered controlled release of Epi C, providing a novel approach for the OA-OCD treatment.

✓ 已验证 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2026 · IF 8.7

Sequential Drug Release from Dual-Responsive Scaffold with Ultrasound-Enhanced Efficacy for Infectious Oral Ulcer Therapy

Li Siyi,Zhang Xiang,Wang Shunan,Jiang Ruonan,Du WenTing,Yi Yin,Shu Yu,Xiu Ziliang,Liang Panpan,Zhou Pengfei,Wu Xiaohong

Oral aphthous ulcers are among the most prevalent mucosal disorders, with infectious oral ulcers severely compromising patients’ quality of life. This study introduces a dual-responsive (ultrasound- and pH-sensitive) hydrogel–microsphere scaffold for their precise, staged management. The scaffold, composed of a pH-sensitive chitosan (CS) hydrogel and ultrasound-responsive sodium alginate (SA) microspheres, demonstrated injectability, biocompatibility, and sequential drug release. Specifically, ultrasound enhanced drug release and tissue penetration, improving therapeutic efficacy. The pH-responsive mechanism enabled targeted release of lidocaine (LID) and curcumin (CUR) at inflamed sites, which is expected to provide local anesthesia while promoting epithelial regeneration. Mechanistically, ultrasound stimulation activated PI3K-Akt and ECM-receptor interaction pathways, which were associated with enhanced cell migration, proliferation, and drug responsiveness. These effects not only enhanced the therapeutic efficacy, but also established a microenvironment favorable for tissue repair. Our platform integrates multimodal functionalities, including rapid release of the analgesic drug LID, followed by the sustained effects of CUR. Crucially, ultrasound facilitate this release process and enhance the therapeutic efficacy. This comprehensive approach modulates the local wound microenvironment, thereby creating favorable conditions for accelerating tissue repair. This work expands new avenues for stimulus-responsive drug delivery systems in the treatment of oral diseases and holds potential for clinical translation.

✓ 已验证 DOI 高影响因子
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Regenerative Biomaterials · 2026 · IF 8.7

Nanoemulsion based on natural components enables oral liver-targeting delivery of Schizandrol B to enhance liver regeneration after hepatectomy in hepatocellular carcinoma

Yi Chen,Jinzhuan Xu,Jing Huang,Huizhou He,Zhimei Cheng,Zhengli Zhou,Man Zhang,Yuanxing Huang,Cao Huang,Jianqing Peng,Shuai Zhang,Runbin Sun,Zipeng Gong

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with partial hepatectomy (PHx) serving as the primary curative treatment. Schizandrol B (SCHB) has demonstrated significant efficacy in promoting liver regeneration and restoring hepatic function following PHx. However, the clinical application of SCHB faces two critical challenges: poor oral bioavailability and inadequate liver-specific targeting. Here, this study developed a nanoemulsion based on natural components named SCHB@SPC/Gal-BSA/DHA. It effectively overcame the limitations of SCHB by synergizing Gal-BSA-mediated liver-specific targeting and DHA-enhanced intestinal absorption, achieving prolonged gastrointestinal tract retention, 2.03-fold higher oral bioavailability and 7.64-fold greater liver accumulation compared to free SCHB. In both 70% PHx and in situ PHx in HCC models, the nanoemulsion robustly accelerated liver regeneration, evidenced by upregulated proliferation markers via STAT3/YAP activation and normalized bile acids metabolism, ultimately restoring liver mass faster than control. This study demonstrates that the dual-targeted nanoemulsion effectively overcomes the key limitations of SCHB by combining enhanced intestinal absorption with liver-specific targeting. The developed nanoemulsion system not only improves drug delivery efficiency but also significantly promotes liver regeneration after PHx, offering a promising therapeutic approach for postoperative recovery in HCC patients while establishing a platform for future liver-targeted oral drug delivery systems.

✓ 已验证 DOI 高影响因子
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Regenerative Biomaterials · 2025 · IF 8.1

A pH-Sensitive CuHP Composite Hydrogel Featuring Antibacterial, Antioxidant, and Osteogenic Properties for Treating Diabetic Periodontitis

Lu Xianwen,Hu Sitong,Zhang Zhaowenbin,Bao Jing,Cao Bangping,Xie Jian,Chang Jiang,Yang Chen,Wang Xiaohong,Su Jiansheng

Periodontitis, a chronic inflammatory disorder primarily induced by bacterial infection and exacerbated by excessive oxidative stress, leads to the destruction of alveolar bone. Diabetes mellitus intensifies this oxidative stress in periodontal tissues and disrupts the oral microbiome, thereby aggravating periodontal conditions and complicating the management of periodontitis. The development of materials that possess comprehensive therapeutic effects, including antibacterial, antioxidant, and osteogenic properties, for the treatment of diabetic periodontitis (DP) remains at the forefront of research. In this study, we introduced a copper hydrogen phosphate (CuHP) composite hydrogel, which exhibited multi-enzymatic activities at varying pH levels. This hydrogel was synthesized by encapsulating CuHP within a commercially available sodium alginate (SA) matrix. In vitro analyses explored the pH-responsive enzymatic activities, biocompatibility, and the antioxidant, osteogenic, and antibacterial properties of the resultant SA/CuHP composite hydrogel. At neutral pH, the hydrogel primarily exhibited catalase-like activity, providing it with antioxidant capabilities that reduced the inhibitory effects of oxidative stress on osteogenesis in bone marrow mesenchymal stem cells. In mildly acidic conditions, the hydrogel displayed peroxidase-like activity, catalysing the production of more potent reactive oxygen species and exhibiting significant antibacterial efficacy against Aggregatibacter actinomycetemcomitans. Furthermore, the SA/CuHP hydrogel continuously released copper ions, which synergistically enhance its osteogenic and antimicrobial efficacies. In vivo studies demonstrated that this composite hydrogel significantly inhibited bacterial growth and promoted bone regeneration in a rat model of DP. These findings suggest that the SA/CuHP hydrogel holds substantial potential for the treatment of periodontitis in patients with diabetes.

CAS / MDL: 10043-52-4
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2025 · IF 8.1

Spatiotemporal Regulation of the Bone Immune Microenvironment via a ‘Zn2+–quercetin’ Hierarchical Delivery System for Bone Regeneration

Sun Hengliang,Chen Yedan,Sang Xiaoqin,Liu Qingxiang,Yu Haoran,Hu Shaojun,Mao Yingji,Zhang Li

The immunoregulation of tissue-engineered bone has emerged as a prominent area for bone defect repair. While this field demonstrates considerable potential, effectively managing relevant factors and maintaining a balanced immune microenvironment in practical applications remain substantial challenges that require resolution. In this study, we tested a novel comprehensive hierarchical delivery system based on the requirements of a natural immune microenvironment for inflammatory factors, to optimize local immune responses through precise regulation of drug release. Quercetin (Que)-loaded zeolite imidazolate framework-8 (ZIF-8) nanoparticles were embedded in gelatin methacrylate (GelMA) to create a drug-release system featuring a Zn2+ shell and quercetin core. In vivo and in vitro studies demonstrated that this dual sustained-release hydrogel-ZIF-8 system can produce low concentrations of Zn2+ at an early stage, resulting in a mild anti-inflammatory effect and proliferation of bone marrow mesenchymal stem cells (BMSCs). Moreover, as inflammation advances, the release of quercetin works synergistically with Zn2+ to enhance anti-inflammatory responses, reconfigure the local microenvironment, and mitigate the inflammatory response that adversely impacts bone health by inhibiting the NF-κB signaling pathway, thereby promoting osteogenic differentiation. This system is pioneering for sequential microenvironment regulation based on its diverse anti-inflammatory properties, offering a novel and comprehensive strategy for bone immune regulation in the clinical treatment of bone defects.

CAS / MDL: 10196-18-6 693-98-1
研究领域: 生物医学工程 · 免疫学 · 骨组织工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2025 · IF 8.1

Photothermal-controlled ICG@ZIF-8/PLGA coating to modify the degradation behavior and biocompatibility of Zn-Li alloy for bone implants

Zhang Ting,Yu Yameng,Yuan Wei,Ren Zeqi,Cheng Yan,Wu Shuilin,Zheng Yufeng,Xia Dandan

Biodegradable Zn alloy have recently gained considerable attention for use in bone implants considering their biodegradability, attractive mechanical properties, and bioactivity. However, excessive corrosion of Zn alloy at the early stage of implantation may cause severe cytotoxicity, resulting in insufficient osseointegration, which hinders the clinical use of the Zn alloy. In this study, we designed a photothermal-controlled degradative hybrid coating as corrosion-protective barrier with the intention of preventing Zn ion burst release during the early stages of implantation and regaining the alloy's corrosion advantage later on. The coating consisting of Zeolite imidazole skeleton-encapsulated indocyanine green core-shell structured nanoparticles and polylactic coglycolic acid (ICG@ZIF-8/PLGA) on pristine Zn-0.8 (wt.%) Li (ZL) alloy. The electrochemical test results indicated that coating ZL with ICG@ZIF-8/PLGA might effectively reduce its corrosion current density (icorr) from 2.48 × 1 0 −5 A•cm−2 to 2.10 × 1 0 −8 A•cm−2. After near-infrared light irradiation, ICG@ZIF-8 heated PLGA coating to reach Tg, so that the coating was degrading, and the icorr of coated ZL alloy decreased to 2.50 × 1 0 −7 A•cm−2, thus restoring corrosion advantage. Both in vitro and in vivo investigations showed that coated ZL alloy had acceptable biocompatibility. Overall, the development of the photothermally controlled coating improved the Zn alloy's resistance to corrosion and allowed for the adjustment of the coated ZL alloy's rate of degradation through the use of 808 nm NIR laser irradiation.

CAS / MDL: 693-98-1
研究领域: 生物医学工程 · 材料科学 · 生物材料 · 组织工程
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