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Black phosphorus nanosheets-enabled DNA hydrogel integrating 3D-printed scaffold for promoting vascularized bone regeneration

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Bioactive Materials 2023年第3期21卷 97-109页

作者： Yali Miao Yunhua Chen Jinshui Luo Xiao Liu Qian Yang Xuetao Shi Yingjun Wang School of Materials Science and engineering South China University of TechnologyGuangzhou510641China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou510006China Key Laboratory of Biomedical engineering of Guangdong Province And Innovation Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou510006China Key Laboratory of Biomedical Materials and engineering of the Ministry of Education South China University of TechnologyGuangzhou510006China

The classical 3D-printed scaffolds have attracted enormous interests in bone regeneration due to the customized structural and mechanical adaptability to bone defects.However,the pristine scaffolds still suffer from the absence of dynamic and bioactive microenvironment that is analogous to natural extracellular matrix(ECM)to regulate cell behaviour and promote tissue regeneration.To address this challenge,we develop a black phosphorus nanosheets-enabled dynamic DNA hydrogel to integrate with 3D-printed scaffold to build a bioactive gel-scaffold construct to achieve enhanced angiogenesis and bone regeneration.The black phosphorus nanosheets reinforce the mechanical strength of dynamic self-healable hydrogel and endow the gel-scaffold construct with preserved protein binding to achieve sustainable delivery of growth factor.We further explore the effects of this activated construct on both human umbilical vein endothelial cells(HUVECs)and mesenchymal stem cells(MSCs)as well as in a critical-sized rat cranial defect model.The results confirm that the gel-scaffold construct is able to promote the growth of mature blood vessels as well as induce osteogenesis to promote new bone formation,indicating that the strategy of nano-enabled dynamic hydrogel integrated with 3D-printed scaffold holds great promise for bone tissue engineering.

关键词： DNA hydrogels 3D-printed scaffold Black phosphorus Vascularized bone regeneration

Heparinized PGA host-guest hydrogel loaded with paracrine products from electrically stimulated adipose-derived mesenchymal stem cells for enhanced wound repair

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再生工程(英文)

再生工程(英文) 2023年第3期4卷 225-237页

作者： Mengyao Li Junliang Li Xueru Xiong Yushi Wang Yong-Guang Jia Xuetao Shi Xiaoling Fu School of Materials Science and engineering South China University of TechnologyGuangzhou 510641China School of Biomedical Sciences and engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China National Engineering Research Center for Tissue Restoration and Reconstruction and Innovation center for tissue restoration and reconstruction Guangzhou 510006China Key Laboratory of Biomedical engineering of Guangdong Province South China University of TechnologyGuangzhou 510006China

The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-guest hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-guest hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.

关键词： Wound repair Electrical stimulation Paracrine factors Heparinized PGA host-guest hydrogel

Wireless electrical stimulation generated by piezoelectric nanomaterial promotes the dental pulp regeneration via regulating mitochondrial Ca^(2+)/PKA signaling pathway

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Journal of Materials Science & Technology 2024年第1期168卷 24-34页

作者： Jianmao Zheng Jiyuan Zuo Cairong Xiao Qining Guo Xiaobin Fu Chengyun Ning Peng Yu Guangdong Provincial Key Laboratory of Stomatology Hospital of StomatologySun Yat-Sen UniversityGuangzhou 510080China School of Materials Science and engineering National Engineering Research Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou 510641China

The induction of dental pulp stem cells(DPSCs)into odontogenic differentiation is a cutting-edge method of dental pulp regeneration treatment.However,it remains a challenge to develop biomaterials and ther-apies that can induce odontogenic differentiation.Here,we propose a wireless electrical stimulation strat-egy to induce DPSCs odontogenic differentiation via K_(0.5)Na_(0.5)NbO_(3)piezoelectric nanoparticles(KNN)and polarized KNN(PKNN),which can be endocytosed by DPSCs.In vitro,several odontogenic differentiation indexes were also increased in DPSCs treated with KNN and PKNN,and the increase was more obvious in the PKNN group.Intracellular wireless electrical field promoted mitochondrial calcium concentration via mitochondrial calcium unidirectional transporter(MCU),increased the production of adenosine triphos-phate(ATP),and induced odontogenic differentiation through the activation of the cAMP-PKA signaling pathway.In vivo,dental pulp-like tissue was induced by electrical stimulation wirelessly with KNN and PKNN,which was more clinically friendly compared with the wired device,and the induction was more obvious in the PKNN group consistent with in vitro experiments.In conclusion,this work demonstrates the potential of PKNN as an effective stimulus that can induce odontogenic differentiation of DPSCs and be applied to dental pulp regeneration treatment.

关键词： Piezoelectric nanoparticles Dental pulp stem cells Odontogenic differentiation

A bioactive glass functional hydrogel enhances bone augmentation via synergistic angiogenesis,self-swelling and osteogenesis

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Bioactive Materials 2023年第4期22卷 201-210页

作者： Fujian Zhao Zhen Yang Huacui Xiong Yang Yan Xiaofeng Chen Longquan Shao Stomatological Hospital Southern Medical UniversityGuangzhou510280China Department of Biomedical engineering School of Materials Science and EngineeringSouth China University of TechnologyGuangzhou510641China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou510006China Guangdong Provincial Key Laboratory of Construction and Detection in tissue engineering Guangzhou510515China

Bone augmentation materials usually cannot provide enough new bone for dental implants due to the material degradation and mucosal pressure.The use of hydrogels with self-swelling properties may provide a higher bone augmentation,although swelling is generally considered to be a disadvantage in tissue engineering.Herein,a double-crosslinked gelatin-hyaluronic acid hydrogels(GH)with self-swelling properties were utilized.Meanwhile,niobium doped bioactive glasses(NbBG)was dispersed in the hydrogel network to prepare the GH-NbBG hydrogel.The composite hydrogel exhibited excellent biocompatibility and the addition of NbBG significantly improved the mechanical properties of the hydrogel.In vivo results found that GH-NbBG synergistically promoted angiogenesis and increased bone augmentation by self-swelling at the early stage of implantation.In addition,at the late stage after implantation,GH-NbBG significantly promoted new bone formation by activating RUNX2/Bglap signaling pathway.Therefore,this study reverses the self-swelling disadvantage of hydrogels into advantage and provides novel ideas for the application of hydrogels in bone augmentation.

关键词： Bioactive glass Bone formation Osteogenesis Angiogenesis

Bioactive glass promotes the barrier functional behaviors of keratinocytes and improves the Re-epithelialization in wound healing in diabetic rats

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Bioactive Materials 2021年第10期6卷 3496-3506页

作者： Fengling Tang Junliang Li Weihan Xie Yunfei Mo Lu Ouyang Fujian Zhao Xiaoling Fu Xiaofeng Chen Department of Biomedical engineering School of Materials Science and EngineeringSouth China University of TechnologyGuangzhou 510641PR China National Engineering Research Center for Tissue Restoration and Reconstruction Guangzhou 510006PR China Key Laboratory of Biomedical engineering of Guangdong Province and Innovation Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou 510006PR China Stomatological Hospital Southern Medical UniversityGuangzhou 510280PR China

Upon skin injury,re-epithelialization must be triggered promptly to restore the integrity and barrier function of the epidermis.However,this process is often delayed or interrupted in chronic wounds like diabetic foot ulcers.Considering that BG particles can activate multiple genes in various cells,herein,we hypothesized that bioactive glass(BG)might be able to modulate the barrier functional behaviors of keratinocytes.By measuring the transepithelial electrical resistance(TEER)and the paracellular tracer flux,we found the 58S-BG extracts substantially enhanced the barrier function of keratinocyte monolayers.The BG extracts might exert such effects by promoting the keratinocyte differentiation and the formation of tight junctions,as evidenced by the increased expression of critical differentiation markers(K10 and involucrin)and TJ protein claudin-1,as well as the altered subcellular location of four major TJ proteins(claudin-1,occludin,JAM-A,and ZO-1).Besides,the cell scratch assay showed that BG extracts induced the collective migration of keratinocytes,though they did not accelerate the migration rate compared to the control.The in vivo study using a diabetic rat wound model demonstrated that the BG extracts accelerated the process of re-epithelialization,stimulated keratinocyte differentiation,and promoted the formation of tight junctions in the newly regenerated epidermis.Our findings revealed the crucial effects of BGs on keratinocytes and highlighted its potential application for chronic wound healing by restoring the barrier function of the wounded skin effectively.

关键词： Bioactive glass Keratinocyte Barrier function Diabetic wound healing

Preface to the Special Issue:Bioadaption of Biomaterials

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Journal of Materials Science & Technology 2016年第9期32卷 799-800页

作者： Yingjun Wang biomaterials and biomedical engineering at south china university of technology chinese academy of engineering chinese society for biomaterials National Engineering Research Center for Tissue Restoration and Reconstruction

tissue repair is always a complex process and artificial biomaterials have never been perfect. For example, the mismatch of mechanical property between biomaterials and the host can result in stress shielding; the asy... 详细信息

关键词： Preface to the Special Issue Bioadaption of Biomaterials

Bioadaptability:An Innovative Concept for Biomaterials

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Journal of Materials Science & Technology 2016年第9期32卷 801-809页

作者： Yingjun Wang National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou 510006China School of Materlals Science and engineering South China University of TechnologyCuangzhou 510640China

Biocompatibility is the basic requirement of biomaterials for tissue repair. However, the present concept of biocompatibility has a certain limitation in explaining the phenomena involved in biomaterial-based tissue repair. New materials, in particular those for tissue engineering and regeneration, have been developed with common characteristics, i.e. they participate deeply into important chemical and biological processes in the human body and the interaction between the biomaterials and tissues is far more complex. Understanding the interplay between these biomaterials and tissues is vital for their development and functionalization. Herein, we suggest the concept of bioadaptability of biomaterials. This concept describes the three most important aspects that can determine the performance of biomaterials in tissue repair： 1） the adaptability of the micro-environment created by biomaterials to the native microenvironment in situ; 2） the adaptability of the mechanical properties of biomaterials to the native tissue; 3） the adaptability of the degradation properties of biomaterials to the new tissue formation. The concept of bioadaptability emphasizes both the material＇s characteristics and biological aspects within a certain micro-environment and molecular mechanism. It may provide new inspiration to uncover the interaction mechanism of biomaterials and tissues, to foster the new ideas of functionalization of biomaterials and to investigate the fundamental issues during the tissue repair process by biomaterials. Furthermore, designing biomaterials with such bioadaptability would open a new door for repairing and regenerating organs or tissues. In this review, we summarized the works in recent years on the bioadaptability of biomaterials for tissue repair applications.

关键词： Bioadaptability Biomaterials Functional design tissue repair

Subcellular localization of chitosan oligosaccharides in living cells

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Chinese Science Bulletin 2014年第20期59卷 2449-2454页

作者： Xian Li Changren Zhou Xiaofeng Chen Mingyan Zhao School of Materials Science and engineering South China University of Technology national engineering research center for Human tissue restoration and reconstruction Department of Materials Science and engineering Jinan University

Chitosan oligosaccharides(COS)is derived from the chemical or enzymatic decomposition of chitosan.The exact mechanisms underlying many biological functions of COS have not been elucidated.Since subcellular localization is very important in determining biological activity in a number of molecules,we used fluorescein isothiocyanate-labeled chitosan oligosaccharides(FITCCOS)and investigated the localization of COS in living cells by laser scanning microscopy.We found that COS entered cells in a dose-and time-dependent manner,and we first showed that COS may enter cells by facilitated passive diffusion and was preferentially localized in the mitochondria.While in high concentration,it was also found in the cytoplasm and nucleus and was enriched in the nucleolus and karyotheca.The different subcellular localization of COS suggested that they played different effects.Determination of COS subcellular localization in cells is important to help us understand the potent mechanisms underlying its multiple functions.

关键词：亚细胞定位活细胞壳聚糖寡糖脱乙酰壳多糖激光扫描显微镜 COS 生物学功能

Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats

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Regenerative Biomaterials 2022年第1期9卷 827-843页

作者： Jing Li Shunshun Yan Weiju Han Zixuan Dong Junliang Li Qi Wu Xiaoling Fu School of Materials Science and engineering South China University of TechnologyGuangzhou 510006China National Engineering Research Center for Tissue Restoration and Reconstruction and Innovation center for tissue restoration and reconstruction Guangzhou 510006China Laboratory of Biomedical engineering of Guangdong Province South China University of TechnologyGuangzhou 510006China School of Biomedical Sciences and engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China

Small extracellular vesicles(sEVs)derived from mesenchymal stem cells(MSCs)can deliver a variety of bioactive factors to create a favorable local microenvironment,thereby holding huge potential in chronic wound repair.However,free sEVs administrated intravenously or locally are usually cleared rapidly,resulting in an insufficient duration of the efficacy.Thus,strategies that enable optimized retention and release profiles of sEVs at wound sites are desirable.Herein,we fabricated novel functional phosphoethanolamine phospholipid-grafted poly-L-lactic acid micro/nanofibers(DSPE-PLLA)to carry and retain sEVs from rat adipose MSCs,enabling the slow local release of sEVs.Our results showed that sEVs@DSPE-PLLA promoted the proliferation,migration and gene expression(ColⅠ,ColⅢ,TGF-β,α-SMA,HIF-1α)of fibroblasts.It also promoted keratinocyte proliferation.In addition,sEVs@DSPE-PLLA helped polarize macrophages toward the M2 phenotype by increasing the expression of anti-inflammatory genes(Arginase 1,CD 206,IL-10)and inhibiting the expression of pro-inflammatory genes(IL-1β,TNF-α).Further in vivo study in diabetic rat models showed that sEVs@DSPE-PLLA improved the wound-healing process by alleviating the inflammatory responses,stimulating cell proliferation,collagen deposition and angiogenesis.These results highlight the potential of using DSPE-grafted scaffolds for extracellular vesicle immobilization and suggest sEVs@DSPE-PLLA micro/nanofibers as promising functional wound dressings for diabetic wounds.

关键词： chronic wound healing small extracellular vesicles sustained release DSPE-PLLA fibers