Regenerative Biomaterials
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2024
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IF 5.6
Wu Sui,Dong Ruichen,Xie Yinhong,Chen Wenhao,Liu Wei,Weng Yajun
During the implantation process of cardiovascular implants, vascular damage caused by inflammation occurs, and the inflammatory process is accompanied by oxidative stress. Currently, carbon monoxide (CO) has been demonstrated to exhibit various biological effects including vasodilatation, antithrombotic, anti-inflammatory, apoptosis-inducing, and antiproliferative properties. In this study hemoglobin/epigallocatechin-3-gallate (EGCG) core-shell nanoparticle containing coating on stainless steel was prepared for CO loading and inflammation modulation. Inspired by strong coordination ability with CO, hemoglobin nanoparticle was first prepared and encapsulated into EGCG metal-phenolic networks. A polydopamine linking layer was then coated on 316 stainless steel, and the hemoglobin/EGCG nanoparticles was loaded with the subsequent polydopamine deposition. It showed that the maximum release amount of CO by the coating was 17.0 nmol/cm2 in 48 hours. In vitro evaluations conducted in a simulated inflammatory environment revealed that the coating, which released CO from hemoglobin/EGCG nanoparticles, effectively mitigated the LPS-induced inflammatory response in macrophages. Specifically, it decreased the expression of TNF-α, increased the expression of IL-10, suppressed the polarization of macrophages towards the M1 phenotype, and reduced intracellular reactive oxygen species (ROS). Furthermore, under simulated oxidative stress conditions, the coating decreased the apoptosis of endothelial cells induced by oxidative stress and downregulated intracellular ROS levels. In vivo implantation results further confirmed that the coating, with its hemoglobin/EGCG nanoparticles and CO release capabilities, reduced macrophage-mediated inflammatory responses and modulated the polarization phenotype of macrophages.
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Diao Zhentian,Li Longkang,Zhou Huan,Yang Lei
Healing of chronic diabetic wounds is challenging due to complications of severe inflammatory microenvironment, bacterial infection and poor vascular formation. Herein, a novel injectable polyvinyl alcohol–hyaluronic acid-based composite hydrogel was developed, with tannic acid (TA) and silicate functionalization to fabricate an ‘all-in-one’ hydrogel PTKH. On one hand, after being locally injected into the wound site, the hydrogel underwent a gradual sol–gel transition in situ, forming an adhesive and protective dressing for the wound. Manipulations of rheological characteristics, mechanical properties and swelling ability of PTKH could be performed via regulating TA and silicate content in hydrogel. On the other hand, PTKH was capable of eliminating reactive oxygen species overexpression, combating infection and generating a cell-favored microenvironment for wound healing acceleration in vitro. Subsequent animal studies demonstrated that PTKH could greatly stimulate angiogenesis and epithelization, accompanied with inflammation and infection risk reduction. Therefore, in consideration of its impressive in vitro and in vivo outcomes, this ‘all-in-one’ multifunctional hydrogel may hold promise for chronic diabetic wound treatment.
研究领域:
生物材料
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医学工程
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再生医学
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DOI
PubMed
高影响因子
Regenerative Biomaterials
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2024
·
IF 5.6
Luo Shengchang,Wang Qingqing,Li Miaoting,Xu Peiyao,Wang Yicheng,Wang Ying,Kankala Ranjith Kumar,Wang Shibin,Chen Aizheng
The decellularized extracellular matrix (dECM) has emerged as an effective medium for replicating the in vivo-like conditions of the tumor microenvironment (TME), thus enhancing the screening accuracy of chemotherapeutic agents. However, recent dECM-based tumor models have exhibited challenges such as uncontrollable morphology and diminished cell viability, hindering the precise evaluation of chemotherapeutic efficacy. Herein, we utilized a tailor-made microfluidic approach to encapsulate dECM from porcine liver in highly poly(lactic-co-glycolic acid) (PLGA) porous microspheres (dECM-PLGA PMs) to engineer a three-dimensional (3D) tumor model. These dECM-PLGA PMs-based microtumors exhibited significant promotion of hepatoma carcinoma cells (HepG2) proliferation compared to PLGA PMs alone, since the infusion of extracellular matrix (ECM) microfibers and biomolecular constituents within the PMs. Proteomic analysis of the dECM further revealed the potential effects of these bioactive fragments embedded in the PMs. Notably, dECM-PLGA PMs-based microtissues effectively replicated the drug resistance traits of tumors, showing pronounced disparities in half-maximal inhibitory concentration (IC50) values, which could correspond with certain aspects of the TME. Collectively, these dECM-PLGA PMs substantially surmounted the prevalent challenges of unregulated microstructure and suboptimal cell viability in conventional 3D tumor models. They also offer a sustainable and scalable platform for drug testing, holding promise for future pharmaceutical evaluations.
研究领域:
生物医学工程
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药学
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癌症研究
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组织工程
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Wang Qiuyu,Zhang Sai,Jiang Jiayi,Chen Shaojuan,Ramakrishna Seeram,Zhao Wenwen,Yang Fan,Wu Shaohua
A dressing patch made of radially oriented poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers was successfully manufactured with a modified electrospinning strategy. The as-electrospun PHBV radially oriented nanofiber dressing patch exhibited uniform and bead-free nanofibrous morphology and innovative radially oriented arrangement, which was demonstrated to possess obviously improved mechanical property, increased surface hydrophilicity, and enhanced biological properties compared to the PHBV nanofiber dressing patch control with traditionally randomly oriented pattern. Interestingly, it was found that the radially oriented pattern could induce the cell migration from the periphery to the center along the radially oriented nanofibers in a rapid manner. In order to further improve the bio-function of PHBV radially oriented nanofiber dressing patch, berberine (Beri, an isoquinoline alkaloid) with two different concentrations were encapsulated into PHBV nanofibers during electrospinning, which were found to present a sustained drug release behavior for nearly one month. Importantly, the addition of Beri could impart the dressing patch with excellent anti-inflammatory property by significantly inhibiting the secretion of pro-inflammatory factors of M1 macrophages, and also showed an additive influence on promoting the proliferation of human dermal fibroblasts (HDFs), as well as inhibiting the growth of E. coli, S. aureus, and C. albicans, compared with the Beri-free dressing patch. In the animal studies, the electrospun PHBV radially oriented nanofiber dressing patch loading with high Beri content was found to obviously accelerate the healing process of diabetic mouse full-thickness skin wound with shortened healing time (100% wound closure rate after 18 days’ treatment) and improved healing quality (improved collagen deposition, enhanced re-epithelialization and neovascularization, and increased hair follicles). In all, this study reported an innovative therapeutic strategy integrating the excellent physical cues of electrospun PHBV radially oriented nanofiber dressing patch with the multiple biological cues of Beri for the effective treatment of hard-to-heal diabetic wounds.
研究领域:
生物医学工程
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材料科学
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伤口愈合
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药学
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组织工程
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Hu Zhaofan,Zhang Yunyang,Zhang Jingjing,Zheng Ran,Yang Yang,Kong Fei,Li Haoran,Yang Xinyan,Yang Shuhui,Kong Xiangdong,Zhao Ruibo
Biomineralization-based cell-material living composites ex vivo showed great potential for living materials construction and cell regulation. However, cells in scaffolds with unconnected pores usually induce confined nutrient transfer and cell–cell communications, affecting the transformation of osteoblasts into osteocytes and the mineralization process. Herein, the osteoblast-materials living hybrids were constructed with porous PLLA microspheres using a rational design, in which cell-based living materials presented an improved osteoblast differentiation and mineralization model using rationally designed cell-microsphere composites. The results indicated that the microfluidic-based technique provided an efficient and highly controllable approach for producing on-demand PLLA microspheres with tiny pores (<5 μm), medium pores (5–15 μm) and large pores (>15 μm), as well as further drug delivery. Furthermore, the simvastatin (SIM)-loaded porous PLLA microsphere with ε-polylysine (ε-PL) modification was used for osteoblast (MC3T3-E1) implantation, achieving the cell-material living microhybrids, and the results demonstrated the ε-PL surface modification and SIM could improve osteoblast behavior regulation, including cell adhesion, proliferation, as well as the antibacterial effects. Both in vitro and in vivo results significantly demonstrated further cell proliferation, differentiation and cascade mineralization regulation. Then, the quantitative polymerase chain reaction or histological staining of typical markers, including collagen type I, alkaline phosphatase, runt-related transcription factor 2 and bone morphogenetic protein 2, as well as the calcium mineral deposition staining in situ, reconfirmed the transformation of osteoblasts into osteocytes. These achievements revealed a promising boost in osteogenesis toward mineralization at the microtissue level by cell-microsphere integration, suggesting an alternative strategy for materials-based ex vivo tissue construction and cell regulation, further demonstrating excellent application prospects in the field of biomineralization-based tissue regeneration.
研究领域:
组织工程
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再生医学
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生物材料学
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DOI
PubMed
高影响因子
Regenerative Biomaterials
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2024
·
IF 5.6
Xie Lijun,Zhang Yan,Cao Binji,Jiao Xiaoyi,Yue Xusong,Xu Yan,Yang Xianyan,Yang Guojing,Wang Yingjie,Shen Jian,Wang Cong,Weng Xisheng,Gou Zhongru
It is known that magnesium phosphate cements (MPCs) show appreciable mechanical strength and biocompatibility, but the hydration reaction processes often lead to intense heat release while the hydration products present weak resistance to mechanical decay and low bioactivity. Herein we developed an MPC-based system, which was low-heat-releasing and fast-curing in this study, by compounding with self-curing calcium silicate cements (CSCs). The MPC composed of magnesium oxide (MgO), potassium dihydrogen phosphate (KH2PO4), disodium hydrogen phosphate (Na2HPO4), magnesium hydrogen phosphate trihydrate (MgHPO4·3H2O) and chitosan were weakly basic, which would be more stable in vivo. The physicochemical properties indicated that the addition of CSCs could increase the final setting time while decrease the heat release. Meanwhile, the CSCs could endow MPC substrate with apatite re-mineralization reactivity, especially, which add 25 wt.% CSCs showed the most significant apatite deposition. What’s more, the mechanical evolution in buffer demonstrated CSCs could enhance and sustain the mechanical strength during degradation, and the internal constructs of cement implants could still be reconstructed by μCT analysis in rabbit femoral bone defect model in vivo. Particularly, appropriate CSCs adjusted the biodegradation and promoted new bone tissue regeneration in vivo. Totally, the MPC/CSCs composite system endows bioactivity and sustain mechanical strength of the MPC, which may be promising for expending the clinical applications of MPC-based bone cements.
研究领域:
材料科学
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生物材料
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生物医学工程
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骨科
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Li Bingyi,He Mei,Xu Zichen,Zhang Qianting,Zhang Liyuan,Zhao Shuang,Cao Yu,Mou Nianlian,Wang Yi,Wang Guixue
Atherosclerosis (AS), an inflammatory disease characterized by lipid accumulation, has a high global incidence and mortality rate. Recently, nanotherapeutic approaches that target pathological sites and improve drug bioavailability and biocompatibility hold great promise for AS treatment. In this study, a biomimetic ROS-responsive hyaluronic acid–based nanomaterial was prepared for targeted anti-AS. Specifically, a safe ROS-responsive carrier based on hyaluronic acid (HSP) was prepared to load methotrexate (MTX), a drug known for its ability to enhance lipid excretion, resulting in the formation of MTX-loaded nanoparticles (MTXNPs). Furthermore, the macrophage membrane was coated on the surface of MTXNPs to obtain MM/MTXNPs. Both MTXNPs and MM/MTXNPs exhibited ROS responsiveness and demonstrated excellent biocompatibility. In vitro experiments revealed that MM/MTXNPs could evade macrophage phagocytosis and exhibited high uptake rates by inflamed endothelial cells. MM/MTXNPs also reduced lipid accumulation in foam cells. In vivo experiments showed that MM/MTXNPs exhibited superior accumulation at AS plaque sites, facilitated by the surface membrane layer containing integrin α4β1 and CD47, resulting in an enhanced therapeutic effect in inhibiting plaque development compared to free MTX and MTXNPs. Therefore, HSP represents a promising nanocarrier to load hydrophobic MTX, enabling effective and biocompatible enhancement of AS treatment.
研究领域:
纳米医学
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药学
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生物医学工程
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心血管疾病
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DOI
PubMed
高影响因子
Regenerative Biomaterials
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2025
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IF 8.1
Wang Xinhui,Fan Xiaoju,Zhai Yuanxin,Li Jie,Sun Huilin,Li Jie,Le Hao,Zhang Feng,Zhang Li,Wang Jianhao,Chu Yun,Cui Pengfei
Intrauterine adhesion (IUA) is a prevalent complication arising from uterine surgery, significantly impacting women’s fertility and overall quality of life. The conventional clinical approach involves hysteroscopic separation of uterine adhesions, though this method poses operational challenges and carries risks of postoperative re-adhesion. Alternatively, the intraoperative placement of intrauterine devices or support balloons can act as a physical barrier to prevent adhesion formation. However, its effectiveness is limited and it may result in secondary damage to the endothelial tissue. To tackle these challenges, we have engineered a temperature-responsive hydrogel incorporating Pluronic HP407/HP188 pharmaceutical excipients and recombinant type III collagen (rCol III) as a bioactive element. Upon in situ injection into the uterine cavity, this hydrogel transitions from a sol–gel phase to a gel in response to body temperature changes, thereby minimizing nonspecific distribution and prolonging the duration of treatment. In vitro studies demonstrate that rCol III temperature-responsive hydrogels exhibit favorable biocompatibility, exhibit a recruitment effect on human endometrial stromal cells, suppress the expression of the fibrotic factor transforming growth factor beta 1 and promote angiogenesis. To evaluate its efficacy in preventing IUA via in vivo experiments, we employed sexually mature female rats for IUA modeling and compared its performance with a commercially available product, cross-linked sodium hyaluronate gel. The results indicate that rCol III temperature-responsive hydrogels significantly enhance retention at the injury site, substantially promote endometrial regeneration, augment endometrial blood supply and reduce abnormal fibrin deposition. This study suggests that rCol III temperature-responsive hydrogels can effectively prevent post-surgical uterine adhesions, highlighting their potential as a promising adhesion prevention strategy.
研究领域:
妇科学
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生物材料学
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再生医学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
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2024
·
IF 5.6
Zhang Ju,Shan Hui,Guo Jinglin,Wang Xiaoying,Wang Weiwei
Due to its highly insidious and rapid progression, deep tissue pressure injury (DTPI) is a clinical challenge. Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accumulation. Decellularized skeletal muscle matrix (dECM) hydrogel promotes skeletal muscle injury repair. However, its role in polarizing macrophages and regulating iron metabolism in DTPI remains unclear. Here, porcine dECM hydrogel was prepared, and its therapeutic function and mechanism in repairing DTPI were investigated. The stimulus of dECM hydrogel towards RAW264.7 cells resulted in a significantly higher percentage of CD206+ macrophages and notably decreased intracellular divalent iron levels. In mice DTPI model, dECM hydrogel treatment promoted M1 to M2 macrophage conversion, improved iron metabolism, and reduced oxidative stress in the early stage of DTPI. In the remodeling phase, the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair. Furthermore, the immunomodulation of dECM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway, as revealed by GO and KEGG pathway analysis, which may ameliorate the iron deposition and promote the healing of DTPI. Our findings indicate that dECM hydrogel is promising in skeletal muscle repair, inflammation resolution, and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.
研究领域:
组织工程
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免疫学
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伤口愈合
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肌肉骨骼疾病
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
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2024
·
IF 5.6
Ji Minrui,Yuan Zaixin,Ma Hongdong,Feng Xian,Ye Cong,Shi Lei,Chen Xiaodong,Han Fei,Zhao Caichou
The management of full-thickness skin injuries continues to pose significant challenges. Currently, there is a dearth of comprehensive dressings capable of integrating all stages of wound healing to spatiotemporally regulate biological processes following full-thickness skin injuries. In this study, we report the synthesis of a dandelion-shaped mesoporous strontium-gallium microparticle (GE@SrTPP) achieved through dopamine-mediated strontium ion biomineralization and self-assembly, followed by functionalization with gallium metal polyphenol networks (MPNs). As CroCfunctional wound dressing, GE@SrTPP can release bioactive ions in a spatiotemporal manner akin to dandelion seeds. During the early stages of wound healing, GE@SrTPP demonstrates rapid and effective hemostatic performance while also exhibiting antibacterial properties. In the inflammatory phase, GE@SrTPP promotes M2 polarization of macrophages, suppresses the expression of pro-inflammatory factors, and decreases oxidative stress in wounds. Subsequently, during the stages of proliferation and tissue remodeling, GE@SrTPP facilitates angiogenesis through the activation of the HIF-1α/VEGF pathway. Analogous to the dispersion and rooting of dandelion seeds, the root-like new blood vessels supply essential nutrients for wound healing. Ultimately, in a rat chronic wound model, GE@SrTPP achieved successful full-thickness wounds repair. In summary, these dandelion-shaped GE@SrTPP microparticles demonstrate comprehensive regulatory effects in managing full-thickness wounds, making them highly promising materials for clinical applications.
研究领域:
材料科学
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生物医学工程
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伤口愈合
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生物材料
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhong Jun,Zhu Mingzhi,Guo Jiaqi,Chen Xinyu,Long Ruimin,Körte Fabian,Wang Shibin,Chen Hao,Xiong Xin,Liu Yuangang
Significant progress has been achieved in tumor therapies utilizing nano-enzymes which could convert hydrogen peroxide into reactive oxygen species (ROS). However, the ROS generated by these enzymes possess a short half-life and exhibit limited diffusion within cells, making it challenging to inflict substantial damage on major organelles for effective tumor therapy. Therefore, it becomes crucial to develop a novel nanoplatform that could extend radicals half-life. Artesunate (ATS) is a Fe (II)-dependent drug, while the limited availability of iron(II), coupled with the poor aqueous solubility of ATS, limits its application. Here, Prussian Blue (PB) was selected as a nano-carrier to release Fe (II), thus constructing a hollow Prussian blue/artesunate/methylene blue (HPB/ATS/MB) nanoplatform. HPB degraded and released iron(III), ATS and MB, under the combined effects of NIR irradiation and the unique tumour microenvironment. Moreover, Fe (III) exploited GSH to formation of Fe (II), disturbing the redox homeostasis of tumor cells, and Fe (II) reacted with H2O2 and ATS to generate carbon radicals with a long half-life in situ. Furthermore, MB generates 1O2 under laser irradiation conditions. In vitro and in vivo experiments have demonstrated that the HPB/ATS/MB NPs exhibit a synergistic therapeutic effect through photothermal therapy, photodynamic therapy and radical therapy.
研究领域:
纳米医学
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肿瘤学
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药理学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhu Delong,Hu Ying,Kong Xiangkai,Luo Yuansen,Zhang Yi,Wu Yu,Tan Jiameng,Chen Jianwei,Xu Tao,Zhu Lei
Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance Exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D printed microfiber culture derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the hyaluronic acid (HA)-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.
研究领域:
再生医学
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组织工程
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生物材料科学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）