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Frontiers in Bioengineering and Biotechnology · 2020 · IF 3.644

Copper Sulfide Nanoparticles-Incorporated Hyaluronic Acid Injectable Hydrogel With Enhanced Angiogenesis to Promote Wound Healing

Zhou Wencheng,Zi Liu,Cen Ying,You Chao,Tian Meng

Skin wound caused by trauma, inflammation, surgery, or burns remains a great challenge worldwide since there is no effective therapy available to improve its clinical outcomes. Herein, we report a copper sulfide nanoparticles-incorporated hyaluronic acid (CuS/HA) injectable hydrogel with enhanced angiogenesis to promote wound healing. The prepared hydrogel could not only be injected to the wound site but also exhibited good photothermal effect, with temperature increasing to 50°C from room temperature after 10 min of near-infrared light irradiation. The cell culture experiments also showed that the hydrogel has no cytotoxicity. In the rat skin wound model, the hydrogel treated wounds exhibited better healing performances. Masson’s trichrome staining suggested that collagen deposition in wounds treated with the hydrogel was significantly higher than other groups. The immunohistochemical staining showed that the hydrogel can effectively upregulate the expression of vascular endothelial growth factor (VEGF) in the wound area at the incipient stage of healing, and the CD 31 immunofluorescence staining confirmed the enhanced angiogenesis of the hydrogel. Taken together, the prepared CuS/HA hydrogel can effectively increase the collagen deposition, upregulate the expression of VEGF, and enhance the angiogenesis, which may contribute to promote wound healing, making it a promising for application in treating skin wound.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 伤口愈合 · 纳米技术
✓ 已验证 DOI PubMed 高影响因子
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Journal of Bionic Engineering · 2021 ·Vol. 18 ·期 6 ·1378-1390 · IF 2.682

Electrospun Scaffold of Collagen and Polycaprolactone Containing ZnO Quantum Dots for Skin Wound Regeneration

Li Pengfei,Ruan Liming,Wang Ruofan,Liu Tianqi,Song Gao,Gao Xiaofei,Jiang Guohua,Liu Xiaoyan

Nanofibers (NFs) have been widely used in tissue engineering such as wound healing. In this work, the antibacterial ZnO quantum dots (ZnO QDs) have been incorporated into the biocompatible poly (ε-caprolactone)/collagen (PCL/Col) fibrous scaffolds for wound healing. The as-fabricated PCL-Col/ZnO fibrous scaffolds exhibited good swelling, antibacterial activity, and biodegradation behaviors, which were beneficial for the applications as a wound dressing. Moreover, the PCL-Col/ZnO fibrous scaffolds showed excellent cytocompatibility for promoting cell proliferation. The resultant PCL-Col/ZnO fibrous scaffolds containing vascular endothelial growth factor (VEGF) also exhibited promoted wound-healing effect through promoting expression of transforming growth factor-β (TGF-β) and the vascular factor (CD31) in tissues in the early stages of wound healing. This new electrospun fibrous scaffolds with wound-healing promotion and antibacterial property should be convenient for treating wound healing.

研究领域: 组织工程 · 伤口愈合 · 生物材料 · 纳米技术 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Microneedle Delivery Platform Integrated with Codelivery Nanoliposomes for Effective and Safe Androgenetic Alopecia Treatment

Shuting Zhang,Hong Zhou,Xuan Chen,Shasha Zhu,Dan Chen,Dan Luo,Siyuan Chen,Wei Liu

Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, β-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.

研究领域: 药学 · 纳米技术 · 皮肤科 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2021 · IF 8.947

Soft apoptotic-cell-inspired nanoparticles persistently bind to macrophage membranes and promote anti-inflammatory and pro-healing effects

Guanglin Zhang,Haoyu Xue,Dazheng Sun,Shenyu Yang,Mei Tu,Rong Zeng

Macrophages play a key role in inflammation, infection, cancer, and repairing damaged tissues. Thus, modulating macrophages with engineered nanomaterials is an important therapeutic strategy for healing chronic inflammatory injuries. However, designing and manufacturing therapeutic nanomaterials remains challenging. Therefore, in this study, apoptotic-cell-inspired deformable phosphatidylserine (PS)- containing nanoliposomes (D-PSLs) with a Young's modulus (E) of approximately 0.5 kPa were constructed via a facile and scalable method. Compared with similar-sized conventional PSLs with an E of approximately 80 kPa, the d -PSLs had a lower uptake efficacy, a much longer binding time to the cell surface, and induced enhanced anti-inflammatory and pro-healing effects via the synergistic effects of their mechanical stimulus and PS-receptor mediation after recognition by macrophages. In particular, chronic wound healing in diabetic rats showed that d -PSLs can efficiently promote M2-like macrophage polarization, increase the expression of the vascular endothelial marker CD31 and accelerate wound closure. Our findings suggest that soft d -PSLs represent a promising biomimetic nano-therapeutic approach for macrophage immunotherapy for chronic inflammatory injury, and that the mechanical stimulus of nanomaterials significantly affects the receptor-mediated biological responses, which will inspire the design of engineered nanomaterials for biomedical applications. Statement of significance Macrophages play a significant role in restoring tissue homeostasis by modulating inflammation and wound healing. Specifically, an M1/M2 macrophage imbalance contributes to various inflammatory disorders. However, modulating macrophages with engineered nanomaterials remains a challenge. In this study, apoptotic-cell-inspired deformable phosphatidylserine (PS)- containing nanoliposomes (D-PSLs) were constructed to explore their interactions with macrophages, and evaluate their anti-inflammatory and pro-healing effects on chronic wounds in diabetic rats. We found that soft d -PSLs can persistently bind to macrophage membranes and enhance the anti-inflammatory and pro-healing responses of macrophages, which not only sheds new light on the design of therapeutic biomaterials based on regulating macrophages but also provide a promising biomimetic nano-therapeutic approach for chronic inflammatory injury.

研究领域: 纳米技术 · 生物医学工程 · 免疫学 · 组织工程 · 药学
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

A Multifunctional, Tough, Stretchable, and Transparent Curcumin Hydrogel with Potent Antimicrobial, Antioxidative, Anti-inflammatory, and Angiogenesis Capabilities for Diabetic Wound Healing

Xianmou Fan,Jun Huang,Wanjun Zhang,Zhihong Su,Jin Li,Zeyong Wu,Peihua Zhang

The treatment of diabetic chronic wounds is still faced with great challenges, mainly due to wound infection, excessive inflammation, and peripheral vascular disease in the wound area. Therefore, it is of great importance to develop a novel multifunctional hydrogel with high efficiency to accelerate diabetic wound healing. Curcumin (Cur), a Chinese herbal, has shown great potential in enhancing the healing of diabetic chronic wounds because of its immunomodulatory and pro-angiogenic properties. However, its low aqueous solubility, poor bioavailability, and chemical instability have limited its clinical applications. To address these current bottlenecks, novel poly(vinyl alcohol) (PVA)–chitosan (CS)/sodium alginate (SA)–Cur (PCSA) hydrogels were prepared for the first time, and they demonstrated all of the above intriguing performances by the Michael addition reaction of CS and Cur. PCSA hydrogels show multiple dynamic bonds, which possess strong mechanical properties (tensile stress: ∼0.980 MPa; toughness: ∼258.45 kJ/m3; and compressive strength: ∼7.38 MPa at strain of 80%). These intriguing performances provided an optimal microenvironment for cell migration and proliferation and also promoted the growth of blood vessels, leading to early angiogenesis. Importantly, the experimental results demonstrated that PCSA hydrogels can effectively transform pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages without the need for additional ingredients in vitro. Benefiting from these characteristics, a full-thickness diabetic wound in a rat model demonstrated that PCSA hydrogels can effectively accelerate wound healing via ROS-scavenging, downregulation of IL-1β, and upregulation of CD31 expression, resulting in angiogenesis and collagen deposition. This strategy not only provides a simple and safe Cur-based hydrogel for diabetic wound healing but also highlights the significant potential for the development of high-performance biomaterials for promoting diabetic wound healing using traditional Chinese medicine.

研究领域: 生物材料 · 伤口愈合 · 药剂学 · 材料科学 · 生物医学工程 · 传统中药
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

In situ photo-crosslinking silk fibroin based hydrogel accelerates diabetic wound healing through antibacterial and antioxidant

Zhendong Guo,Lisi Yan,Bo Zhou,Peiwen Zhao,Wenyuan Wang,Siyan Dong,Bo Cheng,Jing Yang,Xinyu Wang,Binbin Li

Bacterial infection and excessive reactive oxygen species (ROS) in diabetic wounds lead to a prolonged inflammatory phase, and injuries are highly susceptible to developing into chronic wounds. Improving the poor microenvironment is vital to achieving effective diabetic wound healing. In this work, methacrylated silk fibroin (SFMA) was combined with ε-polylysine (EPL) and manganese dioxide nanoparticles (BMNPs) to form an [email protected] (EPL-BM) hydrogel with in situ forming, antibacterial and antioxidant properties. EPL imparted high antibacterial activity (>96 %) to the hydrogel. BMNPs and EPL showed good scavenging activity against a variety of free radicals. [email protected] (EPL-BM) hydrogel had low cytotoxicity and could alleviate H 2 O 2 -induced oxidative stress in L929 cells. In diabetic wounds infected with Staphylococcus aureus ( S. aureus ), the [email protected] (EPL-BM) hydrogel exhibited better antibacterial properties and reduced wound ROS levels more significantly than that of the control in vivo. In this process, the pro-inflammatory factor TNF-α was down-regulated, and the vascularization marker CD31 was up-regulated. H&E and Masson staining showed a rapid transition from the inflammatory to the proliferative phase of the wounds, with significant new tissue and collagen deposition. These results confirm that this multifunctional hydrogel dressing holds well potential for chronic wound healing.

研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 纳米技术 · 药剂学
✓ 已验证 DOI PubMed 高影响因子
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INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED · 2023 · IF 2.5

Combination of PDGF-BB and adipose-derived stem cells accelerated wound healing through modulating PTEN/AKT pathway

Fangyuan Lai,Shijie Dai,Ye Zhao,Yi Sun

Adipose-derived stem cells (ADSCs) have been widely proven to facilitate wound healing. Our study aimed to estimate the influence of combined ADSCs and platelet-derived growth factor-BB (PDGF-BB) on wound healing. We utilized 4 healthy SD rats to isolate ADSCs. Platelet-rich plasma (PRP) was acquired utilizing a two-step centrifugation technology. The role of PRP, PDGF-BB, and PDGF-BB combined with a PI3k inhibitor LY294002 on the viability, migration, and PTEN/AKT pathway in ADSCs were examined utilizing CCK-8, Transwell, and western blot assays. Then, we constructed an open trauma model in SD rats. Effects of ADSCs treated with PDGF-BB on pathological changes, CD31, and PTEN/AKT pathway of wound closure were assessed by hematoxylin & eosin (H&E) staining, Masson staining, immunohistochemical, and western blot assays, respectively. PRP and PDGF-BB intensified the viability and migration of ADSCs by modulating the PTEN/AKT pathway. Interestingly, LY294002 reversed the role of PDGF-BB on ADSCs. In vivo experiments, combined intervention with ADSCs plus PDGF-BB/PRP facilitated wound closure and ameliorated histological injury. Moreover, combined intervention with ADSCs and PDGF-BB attenuated the PTEN level and elevated the CD31 level as well as the ratio of p-AKT/AKT in the skin tissues. A combination of ADSCs and PDGF-BB facilitated wound healing might associate with the regulation of the PTEN/AKT pathway.

研究领域: 再生医学 · 伤口愈合 · 细胞生物学 · 分子生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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CHINESE JOURNAL OF CHEMISTRY · 2023 ·Vol. 41 ·期 20 ·2657-2663 · IF 5.4

Multi-Functional Supramolecular-Polymeric Hybrid Hydrogel for Promoting Cutaneous Wound Repair†

Qingcong Wei,Liyang Jia,Yuke Wang,Weiwei Zhang,Zhiguo Hu,Qigang Wang,Qing Wu

Comprehensive Summary Supramolecular-polymeric hybrid hydrogels combining advantages of the assembled supramolecular networks and polymeric networks have attracted considerable attention recently. However, they are rarely used as multi-functional wound dressing materials. In this work, we report a supramolecular-polymeric hybrid hydrogel consisting of a co-assembled DBS-COOH/Naproxen network (DBS/NAP) and a polymeric gelatin (G)/quaternary ammonium group (Q) and phenylboronic acid groups (PBA)-grafted chitosan (QCS-PBA) network (G/QCS) for accelerating skin wound healing. The polymeric networks could obviously enhance the mechanical properties of the drug-derived supramolecular networks. Q groups endowed the hydrogel with enhanced antibacterial properties. Borate ester crosslinking between PBA groups and diol groups in DBS-COOH could effectively scavenge reactive radicals. The hybrid hydrogel exhibited tunable mechanical and adhesive properties due to the temperature-responsive gelatin networks. NAP could gradually release from hybrid hydrogel networks thus continuously relieving inflammation. Finally, the biocompatible, adhesive, antibacterial and antioxidant hybrid G/QCS-DBS/NAP gel could promote the in vivo healing stages in a full-thickness wounds with increased collagen deposition, upregulated CD31 expression and down-regulated TNF-α expression. Overall, this multi-functional supramolecular-polymeric hybrid hydrogel exhibited great potential for treating skin defects as promising wound dressing materials.

CAS / MDL: 9000-70-8
研究领域: 材料科学 · 生物医学工程 · 药剂学 · 组织工程
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Advanced Science · 2024 · IF 14.3

Ultrasound-Responsive HBD Peptide Hydrogel with Antibiofilm Capability for Fast Diabetic Wound Healing

Lanlan Zong,Runxin Teng,Huiqi Zhang,Wenshang Liu,Yu Feng,Zhengmao Lu,Yuxiao Zhou,Zhen Fan,Meng Li,Xiaohui Pu

Despite advancements in therapeutic agents for diabetic chronic wounds, challenges such as suboptimal bioavailability, intricate disease milieus, and inadequate delivery efficacy have impeded treatment outcomes. Here, ultrasound-responsive hydrogel incorporated with heparin-binding domain (HBD) peptide nanoparticles is developed to promote diabetic wound healing. HBD peptide, derived from von Willebrand Factor with angiogenic activity, are first engineered to self-assemble into nanoparticles with enhanced biostability and bioavailability. Ultrasound responsive cargo release and hydrogel collapses are first verified through breakage of crosslinking. In addition, desired antioxidant and antibacterial activity of such hydrogel is observed. Moreover, the degradation of hydrogel under ultrasound stimulation into smaller fragments facilitated the deeper wound penetration of ≈400 µm depth. Complete wound closure is observed from diabetic mice with chronic wounds after being treated with the proposed hydrogel. In detail, in vivo studies revealed that hydrogels loaded with HBD peptide nanoparticles increased the levels of angiogenesis-related growth factors (VEGF-A, CD31, and α-SMA) to effectively accelerate wound repair. Overall, this study demonstrates that ultrasound-responsive HBD peptide hydrogel provides a synergistic therapeutic strategy for external biofilm elimination and internal effective delivery for diabetic wounds with biofilm infection.

CAS / MDL: 9005-38-3
研究领域: 生物医学工程 · 药学 · 伤口愈合 · 纳米技术 · 生物材料
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FOLIA HISTOCHEMICA ET CYTOBIOLOGICA · 2022 ·Vol. 60 ·期 3 ·260-270 · IF 1.49

HDAC5 inhibits ovarian angiogenesis in dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome

Ying Wang Yu Wang Yao Chen Qianqian Gao Lihui Hou Xiaoling Feng

Introduction. Abnormal ovarian angiogenesis is a common feature of polycystic ovary syndrome (PCOS), a typical endocrine disorder affecting women of reproductive age. Histone deacetylase 5 (HDAC5) has been documented as a suppressor of angiogenesis. The aim of this study was to explore the effect of HDAC5 on ovarian angiogenesis in a PCOS mouse model. Material and methods. PCOS was induced in female C57BL/6 mice by 20-day administration of dehydroepiandrosterone (DHEA). HDAC5 was over-expressed in PCOS mice by corresponding adenovirus injection. In total, 120 mice were used in this study. Western-blotting, real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, flow cytometry, and co-immunoprecipitation were respectively used to evaluate the effect of HDAC5 on PCOS mice. Results. PCOS ovaries showed a compensatory increase in HDAC5 expression, while HDAC5 over-expression alleviated abnormalities in ovarian morphology and serum hormone levels after PCOS modeling. HDAC5 inhibited ovarian angiogenesis in PCOS mice by regulating angiogenesis-related factors, such as VEGFA, platelet-derived growth factors B and D (PDGFB/D), and angiopoietins 1 and 2 (ANGPT1/2) and CD31. HDAC5 over-expression decreased levels of reactive oxygen species (ROS) and malondialdehyde, while promoting activities of catalase and superoxide dismutase in ovaries of PCOS mice, suggesting its suppressive effects on oxidative stress, an inducer of uncontrolled angiogenesis. Moreover, HDAC5 suppressed activation of angiogenesis-related HIF-1α/VEGFA/VEGFR2 signaling in PCOS ovaries partly via inhibiting VEGFR2 acetylation. Conclusions. This study reveals the protective role of HDAC5 in PCOS by inhibiting ovarian angiogenesis and provides a molecular candidate for PCOS therapy in the future.

CAS / MDL: 53-43-0
研究领域: 内分泌学 · 生殖生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Materials Technologies · 2025 · IF 6.2

Polypropylene Mesh Coated with Dual Cross-Linked Hyaluronic Acid/Polyvinyl Alcohol Composite Hydrogel with Antiadhesion and Angiogenesis Properties for Abdominal Wall Repair

Dandan Wei,Guanhua Jiao,Yinghua Tao,Liuxin Yang,Tao Liu,Fengya Jing,Tianzhu Zhang

Development of an antiadhesion polypropylene (PP) mesh in hernia repair is a recognized need because its efficacy is limited by severe abdominal adhesions. The porous structure of PP mesh can facilitate the integration between prosthetic material and abdominal tissue and promote the repair of abdominal wall defect. Herein, an antiadhesion composite hydrogel coating composed of polyvinyl alcohol (PVA) and hyaluronic acid methacrylate (HAMA) is fabricated on the surface of PP mesh through ultraviolet photopolymerization combined with freezing–thawing method. The resulted composite hydrogel coated PP mesh retain 43.33% of the pore structure by this way. In vitro tests proved the as-prepared PP mesh exhibit excellent hydrophilicity and biocompatibility. Meanwhile, the hydrogel coating shows good stability on the surface of PP mesh in phosphate buffered saline medium. After implantation in a rat abdominal wall defect model, the modified PP mesh effectively prevents the formation of adhesion by reducing inflammatory response and suppressing excessive deposition of collagen fiber. Immunohistochemical staining results demonstrate that the modified PP mesh can not only decrease the expression of IL-6, TNF-α, and CD68 but also promote the expression of CD31. Thus, this type of PP mesh with preventing postoperative adhesions and improving angiogenesis may be a promising clinical prosthetic material.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 外科研究
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Bioactive Materials · 2024 · IF 18

Nano-vibration exciter: Hypoxia-inducible factor 1 signaling pathway-mediated extracellular vesicles as bioactive glass substitutes for bone regeneration

Zetao Wang,Qiyuan Dai,Huitong Luo,Xiyuan Han,Qi Feng,Xiaodong Cao

Bioactive glasses (BG) play a vital role in angiogenesis and osteogenesis through releasing functional ions. However, the rapid ion release in the early stage will cause excessive accumulation of metal ions, which in turn leads to obvious cytotoxicity, long-term inflammation, and bone repair failure. Inspired by the vibration exciter, small extracellular vesicles (sEVs) obtained by treating mesenchymal stem cells with copper-doped bioactive glass (CuBG-sEVs), is prepared as a nano-vibration exciter. The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1 (HIF-1) signaling pathway and its activated autophagy, so as to better exert the osteogenic activity of BG. The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy. Cell experiments showed that CuBG-sEVs are favor to cell recruitment, vascularization and osteogenesis as the enrichment of key miRNAs. The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis. These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.

研究领域: 生物材料 · 组织工程 · 再生医学 · 细胞生物学 · 分子生物学
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