Acta Biomaterialia
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2022
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IF 10.633
Yun Liu,Ting Li,Maolei Sun,Zhiqiang Cheng,Wenyuan Jia,Kun Jiao,Shaoru Wang,Kongzhao Jiang,Yuheng Yang,Zhihui Dai,Liping Liu,Guomin Liu,Yungang Luo
Periodontitis is a chronic inflammatory disease caused by plaque that leads to alveolar bone resorption . In the treatment of periodontitis, it is necessary to reduce the bacterial load and promote alveolar bone regeneration . In this study, zeolitic imidazolate framework-8 (ZIF-8) is used in the treatment of periodontitis, and an injectable photopolymerizable ZIF-8/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z) is constructed. We confirm that ZIF-8 nanoparticles are successfully loaded into GelMA, which demonstrates fluidity and photopolymerizability. GelMA-Z continuously releases Zn 2+ and shows good cytocompatibility. In vitro , GelMA-Z can effectively upregulate the expression of osteogenesis-related genes and proteins, increase alkaline phosphatase activity, promote extracellular matrix mineralization by rat bone mesenchymal stem cells, and exert an obvious antibacterial effect against Porphyromonas gingivalis . In vivo , GelMA-Z reduces the bacterial load, relieves inflammation and promotes alveolar bone regeneration in a rat model. The above results show that GelMA-Z has potential prospects in the treatment of periodontitis. Statement of significance Various methods have been explored for the treatment of periodontitis. However, current regiments have difficulty achieving ideal alveolar bone regeneration. In this study, we constructed a zeolitic imidazolate framework-8 (ZIF-8)/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z). (1) The injectable and photopolymerizable GelMA-Z showed biocompatibility in vitro and in vivo . (2) GelMA-Z continually released zinc ions to promote the osteogenic differentiation of bone mesenchymal stem cells and kill bacteria in vitro . (3) In a rat model, the GelMA-Z pregel solution was used to fill the periodontal pocket and then crosslinked by UV exposure. GelMA-Z can stably remain in the periodontal pocket to reduce the bacterial load, relieve inflammation and promote alveolar bone regeneration. In conclusion, GelMA-Z has great potential for use in the treatment of periodontitis, especially in promoting alveolar bone regeneration.
研究领域:
牙科学
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材料科学
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生物医学工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2024
·Vol. 14
·期 1
·95
·
IF 4.8
Fei Tan,Xuran Li,Xiao Li,Maoxiang Xu,Khawar Ali Shahzad,Lei Hou
Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, in which the patient has intact low-frequency hearing and profound high-frequency hearing pre-operatively. Therefore, the synergistic restoration of dysfunctional cochlear hair cells and the protection of hair cells from ototoxic insults have become a persistent target pursued for this hybrid system. In this study, we developed a composite GelMA/PEDOT:PSS conductive hydrogel that is suitable as a coating for the cochlear implant electrode for the potential local delivery of otoregenerative and otoprotective drugs. Various material characterization methods (e.g.,1H NMR spectroscopy, FT-IR, EIS, and SEM), experimental models (e.g., murine cochlear organoid and aminoglycoside-induced ototoxic HEI-OC1 cellular model), and biological analyses (e.g., confocal laser scanning microscopy, real time qPCR, flow cytometry, and bioinformatic sequencing) were used. The results demonstrated decent material properties of the hydrogel, such as mechanical (e.g., high tensile stress and Young’s modulus), electrochemical (e.g., low impedance and high conductivity), biocompatibility (e.g., satisfactory cochlear cell interaction and free of systemic toxicity), and biosafety (e.g., minimal hemolysis and cell death) features. In addition, the CDR medicinal cocktail sustainably released by the hydrogel not only promoted the expansion of the cochlear stem cells but also boosted the trans-differentiation from cochlear supporting cells into hair cells. Furthermore, hydrogel-based drug delivery protected the hair cells from oxidative stress and various forms of programmed cell death (e.g., apoptosis and ferroptosis). Finally, using large-scale sequencing, we enriched a complex network of signaling pathways that are potentially downstream to various metabolic processes and abundant metabolites. In conclusion, we present a conductive hydrogel-based local delivery of bifunctional drug cocktails, thereby serving as a potential solution to intracochlear therapy of bimodal auditory rehabilitation and diseases beyond.Keywords:conductive hydrogel;hair cell;hair cell regeneration;apoptosis;ferroptosis;cochlear implant;electroacoustic stimulation;GelMA;PEDOT:PSS
研究领域:
生物材料
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生物医学工程
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人工耳蜗学
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再生医学
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耳科学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2025
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IF 5.5
Ying Chen,Wenyi Zhao,Ziyang Liu,Huan Zhou,Zhen Yang,Lei Yang
The high incidence of bone trauma has necessitated the development of multifunctional biomaterial implants with both hemostatic and osteogenic properties to address clinical challenges such as bone nonunion and immune rejection associated with nondegradable bone hemostatic materials. In this study, starch/bioactive glass/GelMA-based self-assembling composite microspheres were developed as a novel bone trauma filler exhibiting dual functions of efficient hemostasis and bone regeneration. These micron-scale composite microspheres can be applied to bone trauma sites during surgical procedures or emergency situations. Upon absorption of blood, self-assembly occurs rapidly through hydroxyl/amino-mediated interfacial interactions, preventing dispersion by blood and facilitating the formation of a stable barrier for emergency hemostasis. Furthermore, the bioactive glass component promotes osseointegration via biomineralization-mediated assembly, while the released bioactive ions enhance the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. This composite microsphere exhibited biodegradable properties and significantly improved cranial bone defect repair in vivo.
研究领域:
生物材料
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生物医学工程
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组织工程
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再生医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Rongjiao Sun,Limei Zhu,Xianzhu You,Rong Chen,Jiante Li,Rongrong Pan,Yueqi Jin,Hua Zhou,Ying Tan,Jiajia Dong,Wanle Hu
5-Aminosalicylic acid (5-ASA) is widely used in the clinical treatment of ulcerative colitis (UC), but its effectiveness is limited by poor patient compliance and inadequate drug retention. Herein, a novel thermoresponsive nanogel (P(NVCL-co-GelMA)) was synthesized through the copolymerization of N-vinylcaprolactam (NVCL) and methacrylated gelatin (GelMA). This nanogel serves as an effective carrier for 5-ASA, transitioning from a sol to a hydrogel at physiological temperatures, thereby enhancing drug retention and reducing leakage. In vitro studies revealed that the nanogel has a lower critical solution temperature of approximately 34 °C and can form a gel within 60 s. It demonstrates superior bioadhesion, biocompatibility, and controlled release of 5-ASA. In a rat model of UC, the 5-ASA-loaded nanogel significantly improved weight loss and disease activity index scores compared to untreated rats. The hydrogel coating acts as a biophysical barrier on the intestinal mucosa, effectively blocking the irritation caused by metabolites and maximizing the therapeutic effect, comparable to that of commercial mesalazine enema (Salofalk). The P(NVCL-co-GelMA) nanogel represents a promising drug delivery system for the treatment of UC, offering extended drug retention, reduced leakage, and enhanced therapeutic efficacy.
研究领域:
药学
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药物递送系统
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结直肠疾病
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产品关联
DOI
高影响因子
Surfaces and Interfaces
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2024
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IF 5.7
Shixian Lin,Yuehan Ouyang,Wensheng Lin,Xingwu Zhou,Mengyao Miao,Erzhuo Cheng,Yong Jiang,Zixiang Meng,Man Jin,Sen Zhang,Shiqing Li,Xiaoyu Lv,Shile Chen,Yuchen Guo,Jiayi Zhang,Kaiyin Cai,Zishan Lin,Fanwen Yang,Jixiang Zhu
Microneedle (MN) patches have shown great potential for interstitial fluid (ISF) sampling and subsequent analytes detection, providing an alternative pathway for clinical diagnosis based on blood tests. However, MNs based detection is generally based on separate downstream assays, which cannot provide the detection in real-time. Specifically in the context of glucose monitoring, it is desirable to know the glucose level rapidly so as to guide the subsequent treatment in patients. Here, we designed a double layer MNs patch with the crosslinked gelatin methacryloyl (GelMA) tips loaded with glucose oxidase (GOx), whereas the substrate loaded with horseradish peroxidase (HRP), and 3,3′,5,5′-tetramethylbenzidine (TMB). The MNs tips allow for the ISF sampling and detect the glucose in situ via an enzymatic cascade reaction. We used 3D printing technology for MNs molding, which facilitate the customizable MNs design and optimization. Furthermore, we improved the detection sensitivity and accuracy by optimizing the microenvironment of the GelMA and the concentration of each enzymes. The performance of this MNs patch is validated in extracting and detecting glucose using an agarose gel based skin model. The results showed that within the glucose concentration range of 1.7–21 mmol/L, the MNs patch could accurately measure the unknown glucose concentration through the color values of red, green, and blue (RGB) obtained from scanned images. The all-in-one MNs patch with colorimetric functionality is easy to use and does not require specialized personnel or large-scale equipment support, making it highly promising for clinical translation and providing real -time blood glucose monitoring for patients.
研究领域:
生物医学工程
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材料科学
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分析化学
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医疗器械
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Xiaoyuan Yan,Na An,Zeying Zhang,Qiujing Qiu,Di Yang,Penggong Wei,Xiyue Zhang,Lihong Qiu,Jiajie Guo
Background In bone tissue engineering (BTE), cell-laden scaffolds offer a promising strategy for repairing bone defects, particularly when host cell regeneration is insufficient due to age or disease. Exogenous stem cell-based BTE requires bioactive factors to activate these cells. Graphene oxide quantum dots (GOQDs), zero-dimensional derivatives of graphene oxide, have emerged as potential osteogenic nanomedicines. However, constructing biological scaffolds with GOQDs and elucidating their biological mechanisms remain critical challenges.Methods We utilized GOQDs with a particle size of 10 nm, characterized by a surface rich in C–O–H and C–O–C functional groups. We developed a gelatin methacryloyl (GelMA) hydrogel incorporated with GOQDs-treated dental pulp stem cells (DPSCs). These constructs were transplanted into rat calvarial bone defects to estimate the effectiveness of GOQDs-induced DPSCs in repairing bone defects while also investigating the molecular mechanism underlying GOQDs-induced osteogenesis in DPSCs.Results GOQDs at 5 μg/mL significantly enhanced the osteogenic differentiation of DPSCs without toxicity. The GOQDs-induced DPSCs showed active osteogenic potential in three-dimensional cell culture system. In vivo, transplantation of GOQDs-preactivated DPSCs/GelMA composite effectively facilitated calvarial bone regeneration. Mechanistically, GOQDs stimulated mitophagy flux through the phosphatase-and-tensin homolog-induced putative kinase 1 (PINK1)/Parkin E3 ubiquitin ligase (PRKN) pathway. Notably, inhibiting mitophagy with cyclosporin A prevented the osteogenic activity of GOQDs.Conclusion This research presents a well-designed bionic GOQDs/DPSCs/GelMA composite scaffold and demonstrated its ability to promote bone regeneration by enhancing mitophagy. These findings highlight the significant potential of this composite for application in BTE and underscore the crucial role of mitophagy in promoting the osteogenic differentiation of GOQDs-induced stem cells.
研究领域:
生物医学工程
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组织工程
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纳米技术
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干细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
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2025
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IF 5.7
Wenyong Gao,Can Tang,Diancheng Hang,Hao Chen,Dongsheng Li,Youjie Yan,Wuchang Wang,Hao Peng,Xianmin Wang,Enpeng Zhang,Min Wei,Hengzhu Zhang,Xiaodong Wang
Acute spinal cord injury (SCI) induces mitochondrial oxidative stress, cellular bioenergetic crises, impaired protein degradation, and subsequent degeneration, resulting in increased neuronal vulnerability. Transplantation of exogenous mitochondria to the injury site mitigates cellular energy crises and counteracts neurodegeneration; however, the limited efficacy of mitochondrial transplantation alone constrains its therapeutic potential. In this study, we established a right-sided spinal cord hemisection model at the T10 thoracic segment in rats and transplanted a methacrylate-based gelatin (GelMA) hydrogel containing active mitochondria at the injury site to assess its therapeutic effects and underlying mechanisms. Our findings indicate that GelMA hydrogel combined with mitochondrial transplantation provides superior therapeutic benefits for SCI compared to mitochondrial transplantation alone. GelMA hydrogel enables sustained mitochondrial release at the injury site, supplying energy, upregulating NF200 expression, and promoting axonal regeneration. Additionally, it enhances M2 macrophage accumulation and improves the local inflammatory microenvironment. The structural framework of GelMA hydrogel further supports axonal regeneration. Footprint gait analysis and Basso, Beattie, and Bresnahan (BBB) motor scoring demonstrated that GelMA hydrogel combined with mitochondrial transplantation significantly improves motor function in the right hind limb of rats with SCI. Consequently, GelMA hydrogel combined with mitochondrial transplantation offers a viable and promising approach for treating spinal cord injury.
研究领域:
神经科学
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生物材料
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再生医学
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细胞治疗
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 11
·2006596
·
IF 13.281
Zuoying Yuan,Xiaojing Yuan,Yuming Zhao,Qing Cai,Yue Wang,Ruochen Luo,Shi Yu,Yuanyuan Wang,Jianmin Han,Lihong Ge,Jianyong Huang,Chunyang Xiong
Cell therapeutics hold tremendous regenerative potential and the therapeutic effect depends on the effective delivery of cells. However, current cell delivery carriers with unsuitable cytocompatibility and topological structure demonstrate poor cell viability during injection. Therefore, porous shape-memory cryogel microspheres (CMS) are prepared from methacrylated gelatin (GelMA) by combining an emulsion technique with gradient-cooling cryogelation. Pore sizes of the CMS are adjusted via the gradient-cooling procedure, with the optimized pore size (15.5 ± 6.0 µm) being achieved on the 30-min gradient-cooled variant (CMS-30). Unlike hydrogel microspheres (HMS), CMS promotes human bone marrow stromal cell (hBMSC) and human umbilical vein endothelial cell (HUVEC) adhesion, proliferated with high levels of stemness for 7 d, and protects cells during the injection process using a 26G syringe needle. Moreover, CMS-30 enhances the osteogenic differentiation of hBMSCs in osteoinductive media. CMS can serve as building blocks for delivering multiple cell types. Here, hBMSC-loaded and HUVEC-loaded CMS-30, mixed at a 1:1 ratio, are injected subcutaneously into nude mice for 2 months. Results show the development of vascularized bone-like tissue with high levels of OCN and CD31. These findings indicate that GelMA CMS of a certain pore size can effectively deliver multiple cells to achieve functional tissue regeneration.
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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细胞治疗
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2024
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IF 4.4
Bo Zhang,Jiaxuan Yan,Yi Jin,Yushun Yang,Xiubo Zhao
In this study, a novel approach was employed to develop a therapeutic system for colorectal cancer treatment. Specifically, a GelMA/SilMA hydrogel loaded with curcumin-shellac nanoparticles (Cur@Lac NPs) was created. A microfluidic swirl mixer was utilized to formulate stable Cur@Lac NPs, ensuring their consistent and effective encapsulation. The pH-specific release of curcumin from the NPs demonstrated their potential for colon cancer treatment. By carefully regulating the ratio of GelMA (gelatin methacrylate) and SilMA (silk fibroin methacrylate), a GelMA/SilMA dual network hydrogel was generated, offering controlled release and degradation capabilities. The incorporation of SilMA notably enhanced the mechanical properties of the dual network matrix, improving compression resistance and mitigating deformation. This mechanical improvement is crucial for maintaining the structural integrity of the hydrogel during in vivo applications. In comparison to the direct incubation of curcumin, the strategy of encapsulating curcumin into NPs and embedding them within the GelMA/SilMA hydrogel resulted in more controlled release mechanisms. This controlled release was achieved through the disintegration of the NPs and the swelling and degradation of the hydrogel matrix. The encapsulating strategy also demonstrated enhanced cellular uptake of curcumin, leveraging the advantages of both NPs and in-situ hydrogel injection. This combination ensures a more efficient and sustained delivery of the therapeutic agent directly to the tumor site. Overall, this approach holds significant promise as a smart drug delivery system, potentially improving the efficacy of colorectal cancer treatments by providing targeted, controlled, and sustained drug release with enhanced mechanical stability and biocompatibility.
研究领域:
药学
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生物医学工程
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癌症治疗
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药物递送系统
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Junxian Hu,Yibo Zhu,Xiaoxiao Li,Zeyu Pang,Xiangwei Li,Huilin Zhang,Yiyang Wang,Pei Li,Qiang Zhou
Medical and conservative treatments for intervertebral disc degeneration (IDD) primarily focus on alleviating symptoms. However, effective curative therapies that promote disc regeneration remain lacking. Recent advancements in disc repair materials offer a potential solution, but identifying effective cytokines for regeneration and developing efficient drug delivery systems are crucial for success. This study demonstrated a negative correlation between AQP3 expression levels and the extent of disc degeneration induced by mechanical overload, as evidenced in both in vivo and in vitro models, suggesting that AQP3 is a key regulator of intervertebral disc (IVD) homeostasis. Moreover, the overexpression of AQP3 or exogenous AQP3 protein significantly repaired degenerated IVDs. As a membrane protein, exogenous AQP3 is challenging for cells to recognize and internalize. To address this issue, we designed liposomes to encapsulate AQP3 and incorporated them into GelMA (AQP3-lipo@GelMA) for targeted repair of IDD resulting from high mechanical pressure. The encapsulation of AQP3 in liposomes improved cellular recognition and uptake, thereby enhancing its functionality at the cell membrane. Additionally, AQP3 within this material inhibited the binding of integrins to sialic acid-binding proteins (IBSP), which subsequently reduced the expression of the downstream integrin αVβ3. This cascade effect indirectly activated the AKT pathway, promoting the survival of NP cells. In vivo experiments, we found that AQP3-lipo@GelMA had an efficient function of repairing degenerated intervertebral disc. This study introduced AQP3-lipo@GelMA as a promising material for clinical applications in IVD repair.
研究领域:
再生医学
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骨科
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生物材料科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Guanlu Shen,Xinxin Si,Lei Qiang,Yihao Liu,Zhiyang Yin,Jing Shan,Pengfei Zheng
Growth plate injuries in children and adolescents often lead to bone bridge formation, resulting in limb deformities due to the limited self-repair capacity of the growth plate. The limitations of traditional treatments prompted interest in the role of the extracellular matrix (ECM) and mechanical environment in tissue repair. Recent research showed that 3D hydrogels could mimic ECM to regulate mesenchymal stem cells (MSCs) differentiation, with MSCs sensing matrix viscoelasticity via Piezo1 and responding through the ROCK signaling pathway. This study aimed to develop a 3D biomimetic hydrogel composed of acellular cartilage matrix methacryloyl (ACMMA) and gelatin methacryloyl (GelMA), with adjustable viscoelasticity via blue light crosslinking time. Hydrogels with low (5 s) and high (20s) modulus were fabricated and loaded with bone marrow mesenchymal stem cells (BMSCs). Results demonstrated that the 5 s hydrogel promoted chondrogenic differentiation and inhibited osteogenesis, effectively preventing bone bridge formation and enhancing growth plate repair in vivo . Mechanistic studies confirmed that the 5 s group did not activate the Piezo1-ROCK pathway, supporting its role in chondrogenic differentiation.
研究领域:
生物医学工程
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组织工程
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干细胞研究
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生物材料
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骨科
✓ 已验证
产品关联
DOI
高影响因子
NPG Asia Materials
·
2022
·Vol. 14
·期 1
·1-11
·
IF 10.761
Chen Zheng,Wang Lin,Chen Chichi,Sun Jie,Luo Junchao,Cui Wenguo,Zhu Can,Zhou Xiaozhong,Liu Xingzhi,Yang Huilin,Shi Qin
Cell-derived extracellular matrix (ECM) has been applied in spinal cord injury (SCI) regeneration because of its various biological functions. However, insufficient mechanical properties limit its wide application. Herein, we developed GelMA/ECM hydrogel fibrous scaffolds (GelMA/ECM scaffolds) that can recruit and enhance the differentiation of neural stem cells (NSCs) by electrospinning and decellularization techniques. Moreover, the GelMA/ECM scaffolds had good mechanical properties and reinforced cell adhesion and proliferation. Compared to GelMA hydrogel fibrous scaffolds (GelMA scaffolds), GelMA/ECM scaffolds promoted more NSCs toward neurons by markedly enhancing the expression of MAP-2 and Tuj-1 and decreasing GFAP expression. In addition, the GelMA/ECM scaffolds significantly reduced the proportion of M1-phenotype macrophages, which is favorable for SCI repair. In vivo, the GelMA/ECM scaffolds recruited NSCs at the injured site, promoted neuron regeneration, and reduced the formation of glial scars and the inflammatory response, which further led to a significant improvement in the functional recovery of SCI. Therefore, this scaffold shows potential in regenerative medicine, mainly in SCI.
研究领域:
再生医学
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生物医学工程
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神经科学
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组织工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）