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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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Regenerative Biomaterials · 2023 · IF 6.7

An injectable hydrogel combining medicine and matrix with anti-inflammatory and pro-angiogenic properties for potential treatment of myocardial infarction

Feng Jiayin,Xing Min,Qian Wenhao,Qiu Jiajun,Liu Xuanyong

One of the main illnesses that put people’s health in jeopardy is myocardial infarction (MI). After MI, damaged or dead cells set off an initial inflammatory response that thins the ventricle wall and degrades the extracellular matrix. At the same time, the ischemia and hypoxic conditions resulting from MI lead to significant capillary obstruction and rupture, impairing cardiac function and reducing blood flow to the heart. Therefore, attenuating the initial inflammatory response and promoting angiogenesis are very important for the treatment of MI. Here, to reduce inflammation and promote angiogenesis in infarcted area, we report a new kind of injectable hydrogel composed of puerarin and chitosan via in situ self-assembly with simultaneous delivery of mesoporous silica nanoparticles (CHP@Si) for myocardial repair. On the one hand, puerarin degraded from CHP@Si hydrogel modulated the inflammatory response via inhibiting M1-type polarization of macrophages and expression of pro-inflammatory factors. On the other hand, silica ions and puerarin released from CHP@Si hydrogel showed synergistic activity to improve the cell viability, migration and angiogenic gene expression of HUVECs in both conventional and oxygen/glucose-deprived environments. It suggests that this multifunctional injectable CHP@Si hydrogel with good biocompatibility may be an appropriate candidate as a bioactive material for myocardial repair post-MI.

CAS / MDL: 9012-76-4
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Regenerative Biomaterials · 2022 · IF 5.763

In situ self-assembly of amphiphilic dextran micelles and superparamagnetic iron oxide nanoparticle-loading as magnetic resonance imaging contrast agents

Jiang Linrui,Zheng Rong,Zeng Ni,Wu Changqiang,Su Hongying

Polymeric micelles have long been considered as promising nanocarrier for hydrophobic drugs and imaging probes, due to their nanoscale particle size, biocompatibility and ability to loading reasonable amount of cargoes. Herein, a facile method for dextran micelles preparation was developed and their performance as carriers of superparamagnetic iron oxide (SPIO) nanocrystals was evaluated. Amphiphilic dextran (Dex-g-OA) was synthesized via the Schiff base reactions between oxidized dextran and oleylamine, and self-assembled in situ into nano-size micelles in the reaction systems. The self-assembling behaviors of the amphiphilic dextran were identified using fluorescence resonance energy transfer technique by detection the energy transfer signal between the fluorophore pairs, Cy5 and Cy5.5. Hydrophobic SPIO nanoparticles (Fe3O4 NPs) were successfully loaded into the dextran micelles via the in situ self-assembly process, leading to a series of Fe3O4 NPs-loaded micelle nanocomposites (Fe3O4@Dex-g-OA) with good biocompatibility, superparamagnetism and strongly enhanced T2 relaxivity. At the magnetic field of 0.5 T, the Fe3O4@Dex-g-OA nanocomposite with particle size of 116.2 ± 53.7 nm presented a higher T2 relaxivity of 327.9 mM−1FemMFe−1·s−1. The prepared magnetic nanocomposites hold the promise to be used as contrast agents in magnetic resonance imaging.

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Regenerative Biomaterials · 2023 · IF 6.7

A viscoelastic alginate-based hydrogel network coordinated with spermidine for periodontal ligament regeneration

Zhang Songbai,Jia Yuanbo,Liu Jingyi,Feng Fan,Wei Zhao,Zhang Min,Xu Feng

Periodontitis can cause irreversible defects in the periodontal ligament (PDL), the regeneration of which is the major obstacle to the clinical treatment of periodontitis. Implanting hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL regeneration. However, existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium, which may have been shown as an important role in tissue regeneration. Meanwhile, the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain elusive. In this study, we developed a bi-crosslinking viscoelastic hydrogel (Alg-PBA/Spd) by integrating phenylboronic acid-modified alginate with anti-inflammatory agent (spermidine) through borate ester and B–N coordination bonds, where spermidine will be released with the degradation of the hydrogel. Alg-PBA/Spd hydrogel is biocompatible, injectable and can quickly adapt to complex periodontal structures due to the dynamic crosslinking. We demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal damage. Our results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.

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Regenerative Biomaterials · 2022 · IF 5.763

Nitric oxide-releasing polyurethane/S-nitrosated keratin mats for accelerating wound healing

Dou Jie,Yang Rong,Jin Xingxing,Li Pengfei,Han Xiao,Wang Lijuan,Chi Bo,Shen Jian,Yuan Jiang

Nitric oxide (NO) plays an important role in wound healing, due to its ability to contract wound surfaces, dilate blood vessels, participate in inflammation as well as promote collagen synthesis, angiogenesis and fibroblast proliferation. Herein, keratin was first nitrosated to afford S-nitrosated keratin (KSNO). As a NO donor, KSNO was then co-electrospun with polyurethane (PU). These as-spun PU/KSNO biocomposite mats could release NO sustainably for 72 h, matching the renewal time of the wound dressing. Moreover, these mats exhibited excellent cytocompatibility with good cell adhesion and cell migration. Further, the biocomposite mats exhibited antibacterial properties without inducing severe inflammatory responses. The wound repair in vivo demonstrated that these mats accelerated wound healing by promoting tissue formation, collagen deposition, cell migration, re-epithelialization and angiogenesis. Overall, PU/KSNO mats may be promising candidates for wound dressing.

CAS / MDL: 540-80-7 920-66-1
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Regenerative Biomaterials · 2022 · IF 5.763

Gold nanorods/tetrahedral DNA composites for chemo-photothermal therapy

He Ziyun,Wang Qiusheng,Zhang Nan,Yan Jianqin,Li Li,Cao Jun,He Bin

Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency. Herein, we constructed a nanocomposite based on gold nanorods (GNRs) and drug-loaded tetrahedral DNA nanostructures (TDN) for chemo-photothermal combinational therapy. Anti-tumor drug doxorubicin (DOX) was loaded via the insertion within GC base pairs of TDN. The aptamer AS1411 was attached to the apex of TDN (ATDN) to target tumor cells. The DOX-loaded DNA tetrahedron (ATDN-DOX) was compressed by the GNRs coated with PEI (GNRs@ATDN-DOX) to realize the photothermal function and lysosome escape. GNRs under the illumination of 808 nm infrared laser showed high photothermal conversion and stability due to the protection of PEI layer. The drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per ATDN. The positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal escape. The nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.

CAS / MDL: 25316-40-9
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Regenerative Biomaterials · 2022 · IF 5.763

Surface carboxylation of iron oxide nanoparticles brings reduced macrophage inflammatory response through inhibiting macrophage autophagy

Deng Di,Fu Shengxiang,Cai Zhongyuan,Fu Xiaomin,Jin Rongrong,Ai Hua

Macrophage autophagy is a common biological response triggered by nanomaterials, which is closely related to the regulation of inflammation. Superparamagnetic iron oxide (SPIO) nanoparticles have been used for study of autophagy response due to their broad biomedical applications. However, few reports have focused on how to regulate the macrophage autophagy response induced by SPIO nanoparticles. In this study, SPIO nanoparticles grafted with carboxyl groups were synthesized and for the comparison of macrophage autophagy with unmodified nanoparticles. The study on the correlation between autophagy and inflammation induced by the two kinds of SPIO nanoparticles was also included, and the one that grafted with carboxyl groups shows a reduction of autophagy and thereby caused a milder inflammatory response. We proposed that the increased amount of albumin adsorption on the surface of carboxylated SPIO nanoparticles, a protein previously proven to attenuate autophagy, can be considered an important reason for reducing autophagy and inflammation. In general, the carboxyl modification of SPIO nanoparticles has been demonstrated to reduce inflammation by inhibiting macrophage autophagy, which may provide some insights for the design of nanomaterials in the future.

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Regenerative Biomaterials · 2022 · IF 5.763

Promoting osteointegration effect of Cu-alloyed titanium in ovariectomized rats

Zhang Xiyue,Liu Hui,Li Ling,Huang Cuishan,Meng Xiangbo,Liu Junzuo,Bai Xueling,Ren Ling,Wang Xinluan,Yang Ke,Qin Ling

Osteoporosis is a common skeletal disease making patients be prone to the osteoporotic fracture. However, the clinical implants made of titanium and its alloys with a poor osseointegration need a long time for healing and easily to loosening. Thus, a new class of Cu-alloyed titanium (TiCu) alloys with excellent mechanical properties and bio-functionalization has been developed. In this study, the osteoporosis modeled rats were used to study the osteointegration effect and underlying mechanism of TiCu. The results showed that after implantation for 4 weeks, TiCu alloy could promote the reconstruction of vascular network around the implant by up-regulating vascular endothelial growth factor expression. After 8 weeks, it could further promote the proliferation and differentiation of osteoblasts, mineralization and deposition of collagens, and then significantly increasing bone mineral density around the implant. In conclusion, TiCu alloy would enhance the fixation stability, accelerate the osteointegration, and thus reduce the risk of aseptic loosening during the long-term implantation in the osteoporosis environment. This study was the first to report the role and mechanism of a Cu-alloyed metal in promoting osteointegration in osteoporosis environment, which provides a new attractive support for the improvement of future clinical applications of Cu-alloyed antibacterial titanium alloys.Open in new tabDownload slide

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Regenerative Biomaterials · 2022 · IF 5.763

Electrospinning of antibacterial and anti-inflammatory Ag@hesperidin core-shell nanoparticles into nanofibers used for promoting infected wound healing

Ren Xiuli,Hu Yanan,Chang Linna,Xu Shibo,Mei Xifan,Chen Zhenhua

Bacterial infection and excessive inflammation are still the main obstacles to wound repair. Thus, antibacterial and anti-inflammation nanomaterials are always attracting for infected wound healing. In this work, ultra-uniform (∼20 nm) and colloidally stable Ag nanoparticles (Ag-Hes NPs) with core-shell structure were prepared by using hesperidin as reducing and capping agent. The obtained Ag-Hes NPs present effective antibacterial properties on both Staphylococcus aureus and Escherichia coli. Ag-Hes NPs also got high 1,1-diphenyl-1-picrylhydrazyl scavenging capability of 69%. Under the package of polyvinyl alcohol and sodium alginate, Ag-Hes NPs were encapsulated into electro spun nanofibers to form hydrogel (Ag-Hes@H). This strategy provides a moisture environment which could enrich and release Ag-Hes NPs gradually. Cell experiments and animal wound healing investigation proved that Ag-Hes@H could promote the proliferation and migration of human umbilical vein endothelial cells and accelerate infected wound healing. Meanwhile, Ag-Hes@H significantly reduced the expression of inflammatory cytokines, including IL-6, MMP9 and TNF-α. Immunohistochemistry data further suggested that Ag-Hes@H accelerated wound closure by promoting collagen deposition and skin cell proliferation. The designed antibacterial and anti-inflammatory Ag-Hes@H has great potential for promoting infected wound healing.

CAS / MDL: 872-50-4
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Regenerative Biomaterials · 2022 · IF 5.763

CuS-PNIPAm nanoparticles with the ability to initiatively capture bacteria for photothermal treatment of infected skin

Wang Zizhen,Hou Zishuo,Wang Peiwen,Chen Fan,Luo Xianglin

Copper sulfide nanoparticles (CuS NPs) have shown great potential in various application fields, especially in biomedical engineering fields. CuS NPs, with the ability to actively capture and kill bacteria and without the worry of biocompatibility, will greatly expand their applications. Herein, a four-arm star thermo-sensitive polyisopropylacrylamide (4sPNIPAm) was used to modify CuS NPs (CuS-PNIPAm NPs). The obtained NPs displayed the controlled release of copper ions and higher photothermal conversion ability in comparison with contrast materials CuS-PEG NPs and CuS NPs. Aggregation of CuS-PNIPAm NPs at above 34°C resulted in capturing bacteria by forming the aggregates of NPs-bacteria. Both Staphylococcus aureus and Escherichia coli co-cultured with CuS-PNIPAm NPs were completely killed upon near-infrared irradiation in minutes. Furthermore, CuS-PNIPAm NPs were verified to be a photothermal agent without toxic effect. In in vivo experiment, the NPs effectively killed the bacteria in the wound and accelerated the process of wound repairment. Overall, photothermal treatment by CuS-PNIPAm NPs demonstrates the ability to actively capture and kill bacteria, and has a potential in the treatment of infected skin and the regeneration of skin tissues. The therapy will exert a far-reaching impact on the regeneration of stubborn chronic wounds.

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