Nano Research
·
2024
·
IF 9.5
Zhu Shengjie,Huang Danqing,Luan Qichen,Li Yang,Gan Jingjing,Zhao Yuanjin,Sun Lingyun
Macrophages play a pivotal role in systemic lupus erythematosus (SLE) therapy. Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization. Here, we present a novel hyaluronic acid methacrylate (HAMA) hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions. The HAMA microparticles loaded with monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) were fabricated by using a microfluidic technology. The released MCP-1 facilitates the aggregation of inflammatory macrophages, after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2, thus restoring immune balance. We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery, modulate immune function, and attenuate the disease symptoms. These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.
研究领域:
药理学
·
免疫学
·
生物医学工程
·
药物递送系统
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自身免疫疾病
✓ 已验证
DOI
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Shuai Chen,Haifeng Chen,Lindan Tan,Vahid Serpooshan
Adhesive tissue engineering scaffold (ATES) devices can be secured on tissues by relying on their intrinsic adhesive properties, hence, avoiding the complications such as host tissue/scaffold damages that are associated with conventional scaffold fixation methods like suturing or bioglue. This study introduces a new generation of three-dimensional (3D) bioprinted ATES systems for use as cardiac patches to regenerate the adult human heart. Tyramine-modified methacrylated hyaluronic acid (HAMA-tyr), gelatin methacrylate (GelMA), and gelatin were used to create the hybrid bioink formulation with self-adhesive properties. ATESs were bioprinted and further modified to improve the adhesion properties. In-depth characterization of printing fidelity, pore size, mechanical properties, swelling behavior, as well as biocompatibility was used to create ATESs with optimal biological function. Following in vitro testing, the ATESs were tested in a mouse model of myocardial infarction to study the scaffold adhesive strength in biological milieu. The method developed in this study can be used to manufacture off-the-shelf ATESs with complex cellular and extracellular architecture, with robust potential for clinical translation into a variety of personalized tissue engineering and regenerative medicine applications.
研究领域:
组织工程
·
再生医学
·
心血管研究
·
生物打印
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Xiangyi Wu,Haofang Zhu,Junyi Che,Ye Xu,Qian Tan,Yuanjin Zhao
Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades, while their short in vivo residence, alloimmune reactions, undesired behaviors, and dramatic losses of cell functions still hinder the translation of them into clinic. Here, inspired by the natural components of stem cell niches, we presented novel microfluidic hydrogel microcarriers with extracellular matrix (ECM)-like composition and adipose-derived stem cells (ADSCs) encapsulation for diabetic wound healing. As the hydrogel was synthesized by conjugating hyaluronic acid methacryloyl (HAMA) onto the Fibronectin (FN) molecule chain (FN-HAMA), the laden ADSCs in the microcarriers showed improved bioactivities and pro-regenerative capabilities. Based on these features, we have demonstrated that these ADSCs microcarriers exhibited significant promotion of neovascularization, follicular rejuvenation, and collagen deposition in a mouse diabetic wound model. These results indicated that the stem cell niche-inspired FN-HAMA microcarriers with ADSCs encapsulation have great clinical potential for diabetic wound treatment.
研究领域:
生物医学工程
·
再生医学
·
组织工程
·
糖尿病研究
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 7
·2933
·
IF 13.3
Xiaoxiao Ma,Xiaohui Zhu,Sheng Lv,Chunyan Yang,Zihao Wang,Meilan Liao,Bohao Zhou,Yiming Zhang,Shiyu Sun,Ping Chen,Zhonghua Liu,Haiyan Chen
Background: The timely management of large-scale wounds and the regeneration of skin appendages constitute major clinical issues. The production of high-precision and customizable artificial skin via 3D bioprinting offers a feasible means to surmount the predicament, within which the selection of bioactive materials and seed cells is critical. This study is aimed at employing skin stem cells and multicomponent hydrogels to prefabricate artificial skin through 3D bioprinting, which enables the regeneration of skin and its appendages. Methods and Results: We employed gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) as bioactive materials, in conjunction with epidermal stem cells (Epi-SCs) and skin-derived precursors (SKPs), to fabricate artificial skin utilizing 3D bioprinting. The photosensitive multicomponent hydrogel, comprising 5% GelMA and 0.5% HAMA, demonstrated excellent printability, suitable solubility and swelling rates, as well as stable mechanical properties. Moreover, this hydrogel exhibited exceptional biocompatibility, effectively facilitating the proliferation of SKPs while maintaining the cellular characteristics of both SKPs and Epi-SCs. The transplantation of this artificial skin into cutaneous wounds in nude mice led to complete wound healing and functional tissue regeneration. The regenerated tissue comprised epidermis, dermis, hair follicles, blood vessels, and sebaceous glands, closely resembling native skin. Remarkably, the artificial skin demonstrated sustained tissue regeneration capacity even after 12 h of in vitro culture, facilitating comprehensive functional skin regeneration. Conclusions: Our research presented a skin repair strategy for prefabricated cell-loaded artificial skin, thereby successfully facilitating the regeneration of the epidermis, dermis, hair follicles, blood vessels, and sebaceous glands within the wound.
研究领域:
组织工程
·
再生医学
·
生物材料科学
·
干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Wenxiao Shi,Yu Feng,Jincheng Tang,Yichang Xu,Wang Wei,Lichen Zhang,Xinzhao Jiang,Zhouye Ding,Kun Xi,Liang Chen,Yong Gu
The innate immune response is crucial to the inflammation, but how neutrophils and macrophages act in bone repair and tissue engineering treatment strategies await clarification. In this study, we found N2 neutrophils release stronger “eat me” signals to induce macrophage phagocytosis which then polarize into the M2c anti-inflammatory phenotype. This is beneficial for bone repair. Guided by this biological mechanism, we filled a mesoporous bioactive glass scaffold (MBG) with HAMA hydrogel loaded with TGFβ1 adenovirus (Ad@H), constructing a genetically engineered composite scaffold (Ad@H/M). The scaffold not only has good hydrophilicity and biocompatibility, but also provides mechanical stress support for bone repair. Adenovirus infection quickly induces N2 neutrophils, upregulating NF-κB and MAPK signaling pathways through Toll-like receptor 4 (TLR4) to promote the inflammatory response and macrophage phagocytosis. Macrophages perform phagocytosis and polarize towards the M2 phenotype, mediating the inflammatory response by inhibiting the PI3K-AKT-NF-κB pathway, maintaining homeostasis of the osteogenic microenvironment. The role of Ad@H/M scaffold in regulating early inflammation and promoting long-term bone regeneration was further validated in vivo. In brief, this study focuses on the cascade of reactions between neutrophils and macrophage subtypes, and reports a composite scaffold that coordinates the innate immune response to promote bone repair. This article is protected by copyright. All rights reserved
研究领域:
生物医学工程
·
免疫学
·
组织工程
·
骨再生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Qilong wang,Zeyu Xu,Xuedi Weng,Min Ni,Michael Adu-Frimpong,Xiaoli Li,Yize Lv,Li Jinghan,Hongran Huang,Yue Sun,Ziyun Wu,Xia Cao
Repair of skin injuries is often hindered by the challenge of neovascularization, particularly in severely damaged wounds that struggle to self-heal, potentially leading to organ dysfunction or even death. Thus, promoting vascularization is crucial for effective skin repair. This study employed electrostatic spraying to fabricate methacrylated hyaluronic acid (HAMA) hydrogel microspheres for encapsulation of ectodermal mesenchymal stem cells (EMSCs), and optimization of the process parameters to assess their biocompatibility. Under in vitro conditions, EMSCs microspheres were successfully induced to differentiate into structures with vascular networks. Additionally, the optimal modification ratio of dopamine-modified hyaluronic acid (HADA) was determined to enhance the adhesive and mechanical properties of the dressing. Based on these findings, a dressing incorporating cell microspheres and adhesive hydrogels was developed. This dressing demonstrated formation of microvascular structures in vitro . Upon in vivo transplantation, it integrated tightly with surrounding tissues, modulated the inflammatory response, and accelerated wound healing in mouse model. This composite dressing, integrating cell-laden microspheres within a hydrogel’s framework, offers a simple and effective approach to promote skin microvascular. Statement of Significance : This study describes a hydrogel dressing that uses electrostatically sprayed methacrylated hyaluronic acid (HAMA) microspheres to encapsulate ectodermal mesenchymal stem cells (EMSCs). The hydrogel composition was optimized using dopamine-modified hyaluronic acid (HADA), which improved adhesion, while methacrylated polyvinyl alcohol (PVAMA) enhanced mechanical strength. This highly effective, low-risk hydrogel dressing promoted angiogenesis and accelerated wound healing. The results of this study highlight the potential of hydrogel dressing for clinical applications in tissue engineering and regenerative medicine, thus providing a promising strategy for the treatment of severe skin injuries.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
生物材料
·
干细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yuping Wang,Yiting Lei,Nan Wang,Jun Zhang,Wenguo Cui,Xiaoji Luo
The challenge of achieving graded regeneration of adjacent tissues remains significant in tissue repair and regeneration. For instance, the disruption of the microenvironment caused by “osteogenesis mobilization” often results in fibrosis of the regenerated cartilage, ultimately leading to osteoarthritis. Inspired by the utilization of activated carbon for adsorbing and filtering small particles in air purification and water treatment, we have designed an integrated hydrogel scaffold capable of absorbing the endogenous BMP-2 produced by “osteogenesis mobilization”, confining it to the bone defect area, and preventing its diffusion into the cartilage region, thereby facilitating physiological osteochondral gradient regeneration. The osteogenic layer of this integrated scaffold is NHAP-AHAMA-B2A, which captures the BMP-2 produced by “osteogenesis mobilization” and amplifies its osteogenic effect through the grafted peptide B2A. This upregulation enhances the expression of ALP, OCN, and OPN in MSCs within the osteogenic layer, promoting osteogenic differentiation. The chondrogenic layer, HAMA-B2A, utilizes the peptide B2A to upregulate the expression of COL II and ACAN in MSCs, fostering chondrogenic differentiation. This integrated HAMA-B2A/NHAP-AHAMA-B2A hydrogel scaffold confines the BMP-2 produced by “osteogenesis mobilization” to the bone defect area, prevents its diffusion into the cartilage defect area, and effectively utilizes it to induce stem cell osteogenic differentiation. Simultaneously, it induces stem cell chondrogenic differentiation in the cartilage defect area, achieving transparent cartilage regeneration. In summary, the osteogenic and chondrogenic layers of this integrated scaffold collaborate to achieve a physicochemical gradient regeneration of bone-cartilage.
研究领域:
组织工程
·
再生医学
·
生物材料科学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Fenfang Li,Tiantian Xue,Yanteng Xu,Haixia Wang,Enguo Ju,Mingqiang Li,Yu Tao
Acute liver failure (ALF) is a life-threatening disease for which orthotopic liver transplantation remains one of the most effective treatments. Cell therapy, particularly through the transplantation of artificial bioengineered liver grafts, emerges as a promising alternative to the whole liver transplantation in ALF management. However, the limited availability of functional human hepatocytes, the constrained techniques for swiftly creating artificial bioengineered liver grafts, and the poor cellular survival post-transplantation present significant challenges for advancing clinical applications in liver regeneration. In this study, we introduce a novel approach utilizing microfluidics to create cell-laden microgels for fabricating artificial liver microtissues, in which the controlled hepatic differentiation of stem cells and the development of liver microtissues are incorporated. The cell-laden ARGH microgels (GelMA/HAMA microgels containing AuNCs-miRNA) serving as building blocks for rapid engineering tissue construction, demonstrate the capacity for the one-step promotion of hepatic differentiation of stem cells for a short period of time. Additionally, the bioengineered liver microtissues exhibit multiple biological functionalities, including scavenging ROS, modulating inflammatory environment, and promoting angiogenesis, and can maintain long-term stability after transplantation in vivo. Furthermore, our findings reveal that the in vivo transplantation of the bioengineered liver microtissues offers therapeutic benefits in two drug-induced liver failure experimental models. The transcriptome sequencing analysis further elucidates that the microtissue transplantation ameliorated liver failure by improving liver biofunctions, reducing inflammation and oxidative stress, thereby promoting liver regeneration. Overall, this study presents an effective approach leveraging functional biomaterials and microfluidic techniques to fabricate artificial liver microtissues for liver failure treatment.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
微流控技术
·
肝脏病学
·
纳米医学
·
干细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）