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Regenerative Biomaterials · 2023 · IF 6.7

Mitochondrial-targeting Mn3O4/UIO-TPP nanozyme scavenge ROS to restore mitochondrial function for osteoarthritis therapy

Zhang Shengqing,Cai Jinhong,Yao Yi,Huang Lanli,Zheng Li,Zhao Jinmin

Excessive reactive oxygen species (ROS)-induced mitochondrial damage has impact on osteoarthritis (OA). Nanozyme mimics as natural enzyme alternatives to scavenge excessive ROS has offered a promising strategy for OA therapy. Herein, we reported a novel mitochondrial-targeting Mn3O4/UIO-TPP nanozyme using metal-organic frameworks (MOFs) with loaded Mn3O4 as the enzyme-like active core combining mitochondria-targeting triphenylphosphine (TPP) groups to serve as ROS scavengers for therapy of OA. With sequential catalysis of superoxide dismutase (SOD)-like, catalase (CAT)-like, and hydroxyl radical (·OH) scavenging potentials, the nanozyme can target mitochondria by crossing subcellular barriers to effectively eliminate ROS to restore mitochondrial function and inhibit inflammation and chondrocyte apoptosis. It also has favorable biocompatibility and biosafety. Based on anterior cruciate ligament transection (ACLT)-induced OA joint models, this mitochondrial-targeting nanozyme effectively mitigated the inflammatory response with the Pelletier score reduction of 49.9% after 8-week therapy. This study offers a prospective approach to the design of nanomedicines for ROS-related diseases.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2023 · IF 6.7

Incorporation of kartogenin and silk fibroin scaffolds promotes rat articular cartilage regeneration through enhancement of antioxidant functions

Pan Zejun,Hou Mingzhuang,Zhang Yijian,Liu Yang,Tian Xin,Hu Xiayu,Ge Xiaoyang,Zhao Zhijian,Liu Tao,Xu Yong,Yang Huilin,Liu Hao,Zhu Xuesong,He Fan

Treating articular cartilage defects in patients remains a challenging task due to the absence of blood vessels within the cartilage tissue. The regenerative potential is further compromised by an imbalance between anabolism and catabolism, induced by elevated levels of reactive oxygen species (ROS). However, the advent of tissue engineering introduces a promising strategy for cartilage regeneration, offering viable solutions such as mechanical support and controlled release of chondrogenic molecules or cytokines. In this study, we developed an antioxidant scaffold by incorporating natural silk fibroin (SF) and kartogenin (KGN)-loaded liposomes (SF-Lipo@KGN). The scaffold demonstrated appropriate pore size, connectivity, and water absorption and the sustained release of KGN was achieved through the encapsulation of liposomes. In vitro experiments revealed that the SF-Lipo@KGN scaffolds exhibited excellent biocompatibility, as evidenced by enhanced cell adhesion, migration, and proliferation of chondrocytes. The SF-Lipo@KGN scaffolds were found to stimulate cartilage matrix synthesis through the activation of the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant signaling pathway. In vivo experiments demonstrated the effective promotion of articular cartilage regeneration by the SF-Lipo@KGN scaffolds, which enhanced extracellular matrix anabolism and restored the intrinsic redox homeostasis. Overall, this study successfully developed biomimetic KGN-loaded scaffolds that restore cartilage redox homeostasis, indicating promising prospects for cartilage tissue engineering.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2023 · IF 6.7

Codelivery of dihydroartemisinin and chlorin e6 by copolymer nanoparticles enables boosting photodynamic therapy of breast cancer with low-power irradiation

Jia Jing,Chen Wenping,Xu Long,Wang Xuewen,Li Min,Wang Bin,Huang Xiangyu,Wang Tao,Chen Yang,Li Mengdie,Tian Dan,Zhuang Junyang,Lin Xinhua,Li Ning

Given that chemotherapy as a stand-alone therapeutic strategy may not be sufficient to effectively treat cancer, there is increasing interest in combination of chemotherapy and alternative therapies. Photodynamic therapy has the advantages of high selectivity and low side effects, so the combination of photodynamic therapy and chemotherapy has become one of the most appealing strategies for tumor treatment. In this work, we constructed a nano drug codelivery system (PPDC) to realize the combined treatment of chemotherapy and photodynamic therapy through encapsulating chemotherapeutic drug dihydroartemisinin and photosensitizer chlorin e6 in PEG-PCL. The potentials, particle size and morphology of nanoparticles were characterized by dynamic light scattering and transmission electron microscopy. We also investigated the reactive oxygen species (ROS) generation and drug release ability. The antitumor effect in vitro was investigated by methylthiazolyldiphenyl-tetrazolium bromide assays and cell apoptosis experiments, and the potential cell death mechanisms were explored by ROS detection and Western blot analysis. The in vivo antitumor effect of PPDC was evaluated under the guidance of fluorescence imaging. Our work provides a potential antitumor treatment approach and expands the application of dihydroartemisinin for breast cancer therapy.

CAS / MDL: 90389-85-8
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Regenerative Biomaterials · 2023 · IF 6.7

Bioactive mineralized small intestinal submucosa acellular matrix/PMMA bone cement for vertebral bone regeneration

Miao Xinbao,Yang Shuhui,Zhu Jinjin,Gong Zhe,Wu Dongze,Hong Juncong,Cai Kaiwen,Wang Jiying,Fang Xiangqian,Lu Jiye,Jiang Guoqiang

Polymethylmethacrylate (PMMA) bone cement extensively utilized for the treatment of osteoporotic vertebral compression fractures due to its exceptional handleability and mechanical properties. Nevertheless, the clinical application of PMMA bone cement is restricted by its poor bioactivity and excessively high modulus of elasticity. Herein, mineralized small intestinal submucosa (mSIS) was incorporated into PMMA to prepare a partially degradable bone cement (mSIS–PMMA) that provided suitable compressive strength and reduced elastic modulus compared to pure PMMA. The ability of mSIS-PMMA bone cement to promote the attachment, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells was shown through cellular experiments carried out in vitro, and an animal osteoporosis model validated its potential to improve osseointegration. Considering these benefits, mSIS-PMMA bone cement shows promising potential as an injectable biomaterial for orthopedic procedures that require bone augmentation.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2023 · IF 6.7

Phosphoserine enhanced Cu-doped bioactive glass dynamic dual-network hydrogel for craniofacial bone defect repair

Liu Yuwei,Wang Gang,Luo Huitong,Zhao Bangjiao,Liao Muheng,Dai Qiyuan,Li Maocai,Li Qingtao,Cao Xiaodong

Flexible hydrogels containing various osteogenic inorganic constituents, which can accommodate complicated shape variations, are considered as ideal grafts for craniofacial bone defect reconstruction. However, in most hybrid hydrogels, poor interaction between the polymer network and particles has detrimental effects on hydrogel rheological and structural properties, clinical manipulation and repair efficacy. In this article, we designed and prepared a series of hyaluronic acid composite hydrogel containing Cu-doped bioactive glass (CuBG) and phosphoserine (PS), in which hyaluronic acid was modified by methacrylate groups and phenylboronic acid groups to form a double crosslinked network. PS acted as an interaction bridge of CuBG particles and HAMA-PBA network to improve the mechanical properties of the composite hydrogels. The CuBG/PS hydrogels exhibited suitable rheological properties (injectable, self-healing, shape-adaptable), bone tissue integrating ability and anti-bacterial property. Meanwhile, we found that CuBG and PS have synergistic effect on improving osteogenic efficiency both in vitro and in vivo, particularly when the ratio of CuBG to PS is lower than 3 (9CB/3PS). This work provided a versatile and scalable approach to enhanced the interaction within inorganic particles and polymer network in hydrogels without extra modification on components.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2023 · IF 6.7

An extracellular matrix-mimetic coating with dual bionics for cardiovascular stents

Chen Nuoya,Li Mingyu,Wu Haoshaung,Qin Yumei,Wang Jian,Xu Kai,Luo Rifang,Yang Li,Wang Yunbing,Zhang Xingdong

Anti-inflammation and anti-coagulation are the primary requirements for cardiovascular stents and also the widely accepted trajectory for multi-functional modification. In this work, we proposed an extracellular matrix (ECM)-mimetic coating for cardiovascular stents with the amplified functionalization of recombinant humanized collagen type III (rhCOL III), where the biomimetics were driven by structure mimicry and component/function mimicry. Briefly, the structure-mimic was constructed by the formation of a nanofiber (NF) structure via the polymerization of polysiloxane with a further introduction of amine groups as the nanofibrous layer. The fiber network could function as a three-dimensional reservoir to support the amplified immobilization of rhCoL III. The rhCOL III was tailored for anti-coagulant, anti-inflammatory and endothelialization promotion properties, which endows the ECM-mimetic coating with desired surface functionalities. Stent implantation in the abdominal aorta of rabbits was conducted to validate the in vivo re-endothelialization of the ECM-mimetic coating. The mild inflammatory responses, anti-thrombotic property, promotion of endothelialization and suppression of excessive neointimal hyperplasia confirmed that the ECM-mimetic coating provided a promising approach for the modification of vascular implants.

CAS / MDL: 1760-24-3
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2023 · IF 6.7

Kinetically inert manganese (II)-based hybrid micellar complexes for magnetic resonance imaging of lymph node metastasis

Chen Kai,Cai Zhongyuan,Cao Yingzi,Jiang Lingling,Jiang Yuting,Gu Haojie,Fu Shengxiang,Xia Chunchao,Lui Su,Gong Qiyong,Song Bin,Ai Hua

The localization and differential diagnosis of the sentinel lymph nodes (SLNs) are particularly important for tumor staging, surgical planning and prognosis. In this work, kinetically inert manganese (II)-based hybrid micellar complexes (MnCs) for magnetic resonance imaging (MRI) were developed using an amphiphilic manganese-based chelate (C18-PhDTA-Mn) with reliable kinetic stability and self-assembled with a series of amphiphilic PEG-C18 polymers of different molecular weights (C18En, n = 10, 20, 50). Among them, the probes composed by 1:10 mass ratio of manganese chelate/C18En had slightly different hydrodynamic particle sizes with similar surface charges as well as considerable relaxivities (∼13 mM−1 s−1 at 1.5 T). In vivo lymph node imaging in mice revealed that the MnC MnC-20 formed by C18E20 with C18-PhDTA-Mn at a hydrodynamic particle size of 5.5 nm had significant signal intensity brightening effect and shortened T1 relaxation time. At an imaging probe dosage of 125 μg Mn/kg, lymph nodes still had significant signal enhancement in 2 h, while there is no obvious signal intensity alteration in non-lymphoid regions. In 4T1 tumor metastatic mice model, SLNs showed less signal enhancement and smaller T1 relaxation time variation at 30 min post-injection, when compared with normal lymph nodes. This was favorable to differentiate normal lymph nodes from SLN under a 3.0-T clinical MRI scanner. In conclusion, the strategy of developing manganese-based MR nanoprobes was useful in lymph node imaging.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2023 · IF 6.7

Sustained release of brimonidine from polydimethylsiloxane-coating silicone rubber implant to reduce intraocular pressure in glaucoma

Huang Chang,Shen Yuening,Zhao Yujin,Zhang Zhutian,Gao Shunxiang,Hong Jiaxu,Xu Jianjiang,Meng Qingtao,Sun Xinghuai,Sun Jianguo

Glaucoma is the leading cause of irreversible blindness, affecting 111 million people by 2040 worldwide. Intraocular pressure (IOP) is the only controllable risk factor for the disease and current treatment options seek to reduce IOP via daily taking eye drops. However, shortcomings of eye drops, such as poor bioavailability and unsatisfied therapeutic effects, may lead to inadequate patient compliance. In this study, an effective brimonidine (BRI)-loaded silicone rubber (SR) implant coated with polydimethylsiloxane (BRI@SR@PDMS) is designed and fully investigated for IOP reduction treatment. The in vitro BRI release from BRI@SR@PDMS implant reveals a more sustainable trend lasting over 1 month, with a gradually declined immediate drug concentration. The carrier materials show no cytotoxicity on human corneal epithelial cells and mice corneal epithelial cells in vitro. After administrated into rabbit’s conjunctival sac, the BRI@SR@PDMS implant releases BRI in a sustained fashion and effectively reduces IOP for 18 days with great biosafety. In contrast, BRI eye drops only maintain IOP-lowering effect for 6 h. Therefore, as a substitute of eye drops, the BRI@SR@PDMS implant can be applied as a promising non-invasive platform to achieve long-term IOP-lowering in patients suffering from ocular hypertension or glaucoma.

CAS / MDL: 919-30-2
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Regenerative Biomaterials · 2023 · IF 6.7

68Ga-labeled amphiphilic polymer nanoparticles for PET imaging of sentinel lymph node metastasis

Chen Qin,Fu Xiaomin,Cai Huawei,Fu Shengxiang,Cai Zhongyuan,Li Mufeng,Wu Xiaoai,Tian Rong,Ai Hua

Precise diagnosis of lymph node metastasis is important for therapeutic regimen planning, prognosis analysis and probably better outcomes for cancer patients. In this work, 68Ga-labeled amphiphilic alternating copolymers nanoparticles with different rigid ligands were synthesized as positron emission tomography (PET) probes for lymph node metastasis imaging. The labeling efficiency and stability of nanoparticles was improved with increased rigidity of coordination unit. PU(68Ga-L-MDI-PEG) nanoparticles (PU(68Ga-L-MDI-PEG) NPs) with the strongest rigidity of coordination unit exhibited the lowest critical micelle concentration, the best 68Ga labeling efficiency and stability. During in vivo lymph node metastasis imaging, PU(68Ga-L-MDI-PEG) NPs led to different accumulations in normal lymph nodes (N-LN) and tumor metastasized sentinel lymph nodes (T-SLN), which resulted in different PET signal presentation, making it feasible to differentiate N-LN from T-SLN. In comparison, small molecule probe 68GaL had poor lymph node accumulation, not only making it difficult to find lymph nodes on PET/computed tomography scan, but also tough to distinguish N-LN from metastatic ones. Overall, this work provides a reference for design of 68Ga labeled polymeric nanoparticles with high chelation efficiency and stability, as sensitive PET probes for lymph node imaging.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2023 · IF 6.7

Non-viral gene coating modified IOL delivering PDGFR-α shRNA interferes with the fibrogenic process to prevent posterior capsular opacification

Wang Jiahao,Hu Yulin,Han Yuemei,Fang Qiuna,Chen Zhirong,Wang Yajia,Zhao Peiyi,Wang Hui,Lin Quankui

Posterior capsule opacification (PCO), the most common complication after cataract surgery, is caused by the proliferation, migration and epithelial–mesenchymal transition (EMT) of residual lens epithelial cells in the capsule bag. Although the surface modification and drug loading of intraocular lens (IOLs) have been effective in preventing PCO to some extent, the intraocular safety of anti-proliferative drug application is still a major limitation in clinical application. In this study, we used non-viral gene delivery systems in combination with layer-by-layer (LBL) self-assembly technology, and the modified IOL could effectively prevent the development of PCO by interfering with the EMT process mediated by the platelet-derived growth factor receptor-α (PDGFR-α). Herein, the gene fragments were wrapped by electrostatic conjugation using polyethyleneimine-graft-poly(ethylene glycol) to form gene complexes. Gene complexes were characterized by dynamic light scattering, transmission electron microscopy (TEM) and agarose gel electrophoresis, and evaluated for storage and serum stability. The layer assembly behavior of the IOL surface, changes in optical properties and the release behavior of the gene complexes were characterized using quartz crystal microbalance, UV–vis, contact angle and TEM. In vitro experiments showed that the IOL coating has good bio-compatibility and can achieve the corresponding transfection effect, and the released gene complexes exhibited excellent cell internalization and lysosomal escape behaviors, as well as effective inhibition of PDGFR-α expression and its mediated EMT process. The early PCO prevention effect and bio-compatibility evaluation of the modified IOL in vivo were evaluated by implantation into animal eyes. This study provides a new strategy for the development of surface modifications of small nucleic acid drugs and non-toxic EMT interference therapies for PCO.

CAS / MDL: 100403-24-5 9041-08-1
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Regenerative Biomaterials · 2023 · IF 6.7

Self-assembled supramolecular immunomagnetic nanoparticles through π–π stacking strategy for the enrichment of circulating tumor cells

Mao Yanchao,Zhang Yujia,Yu Yue,Zhu Nanhang,Zhou Xiaoxi,Li Guohao,Yi Qiangying,Wu Yao

Owing to their high-specific binding toward targets as well as fast and convenient separation operations, immunomagnetic beads (IMBs) are widely used in the capture and detection of circulating tumor cells (CTCs). To construct the IMBs, surface modifications are generally performed to functionalize the magnetic cores (e.g. Fe3O4 nanoparticles), and the employed surface modification strategies normally influence the structure and functions of the prepared IMBs in return. Different from the existing work, we proposed the use of supramolecular layer-by-layer (LBL) self-assembly strategy to construct the IMBs. In general, owing to the π–π stacking interactions, the polydopamine, graphene oxide and ‘molecular glue’ γ-oxo-1-pyrenebutyric acid were self-assembled on Fe3O4 nanoparticles sequentially, thereby accomplishing the integration of different functional components onto magnetic cores to prepare the self-assembled supramolecular immunomagnetic beads (ASIMBs). The ASIMBs showed high sensitivity, specificity and good biocompatibility to the model CTCs and low nonspecific adsorption to the negative cells (∼93% for MCF-7 cells and 17% for Jurkat cells). Meanwhile, ASIMBs possessed a remarkable potential to screen the rare MCF-7 cells out of large amounts of interfering Jurkat cells with the capture efficiency of 75–100% or out of mouse whole blood with the capture efficiency of 20–90%. The captured cells can be further recultured directly without any more treatment, which showed huge applicability of the ASIMBs for in vitro detection in clinical practices.

CAS / MDL: 538-75-0 25952-53-8
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Regenerative Biomaterials · 2023 · IF 6.7

Collagen-based injectable and self-healing hydrogel with multifunction for regenerative repairment of infected wounds

Gu Haojie,Li Han,Wei Liren,Lu Jian,Wei Qingrong

At present, the development trend of dressing materials is being multifunctional for convenient and long-term nursing care process of some complicated wounds. Here, basing on the theory of wound moist healing, an injectable and self-healing hydrogel comprising of collagen (COL), chitosan (CS) and oxidation modified Konjac glucomannan (OKGM), which acts as a macromolecular cross-linker to construct dynamic Schiff-base bonds was smartly designed. The strategy of introducing the silver nanoparticles (Ag NPs) into the COL–CS–OKGM hydrogel matrix achieved a markedly enhanced antibacterial activity derived from the synergistical effect between the Ag+ and the mild photothermal efficacy of Ag NPs, which also improved the local capillary blood circulation of the wound area to further facilitate wound healing process. The excellent syringeability and self-healing behaviors endowed the COL–CS–OKGM–Ag hydrogel with self-adapting ability for the wounds with irregular and large area needing frequent applying and changing without secondary injuries. In vitro and in vivo evaluations verified that so-designed COL–CS–OKGM–Ag hydrogel also with hemostatic performance is a promising multifunctional dressing for the treatments of infected wound with not only good biocompatibility and convenient use, but also with desired regenerative healing prognoses benefited from hydrogel moist environment and physiotherapy.

CAS / MDL: 7790-28-5
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