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Effect of Mineralized Layer Topographies on Stem Cell Behavior in Microsphere Scaffold

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Journal of Materials Science & Technology 2016年第9期32卷 971-977页

作者： Jie Hou Huichang Gao Ying,jun Wang Delin Cheng xiaodong cao School of Materials Science and Engineering South China University of TechnologyGuangzhou 510641China National Engineering Research Center for Tissue Restoration and Reconstruction Cuangzhou 510006China Guangdong Province Key Laboratory of Biomedical Engineering South China University of TechnologyGuangzhou 510006China Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy o~SciencesShenzhen 518055China

Modifying substrates through mineralization is a popular way to improve the osteogenic performance. Screening of the best mineralization characteristics on specific substrates for stem cells is meaningful but not fully studied. In this paper, poly（lactic-co-glycolic acid）/hydroxyapatite （PLGA[HA, PH） microsphere scaffolds with superficial pores were fabricated by a low-temperature fusion method. After the mineralization in the 5x stimulated body fluid （SBF） for 0, 7, 12 and 24 h, four mineralized scaffolds （MPH-0, MPH-7, MPH-12 and MPH-24） with different apatite topographies were obtained. It was found that the surface of MPH-7 was evenly decorated with abundant micro-pores, MPH-12 with dense and plain apatite layer, and MPH-24 with small spherical bumps. The responses of mouse bone mesenchymal stem cells （mBMSCs） to the four scaffolds were further studied. The results showed that MPH-7 and MPH-24 had more obvious effects on mBMSCs attachment, proliferation and differentiation than MPH-0 and MPH- 12. This work indicated that to obtain the maximum improvement, the mineralization characteristics had to be carefully chosen. This was noteworthy in the chemical modification of surfaces to form the functionalized scaffolds for bone repair.

关键词： Microsphere scaffold Mineralization Topography Cell behavior

Bilayered HA/CS/PEGDA hydrogel with good biocompatibility and self-healing property for potential application in osteochondral defect repair

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Journal of Materials Science & Technology 2018年第6期34卷 1016-1025页

作者： Baihao You Qingtao Li Hua Dong Tao Huang xiaodong cao Hua Liao School of Materials Science and Engineering South China University of Technology Guangzhou 510641 China National Engineering Research Centre for Tissue Restoration and Reconstruction Guangzhou 510006 China School of Medicine South China University of Technology Guangzhou 510006 China Department of Anatomy Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering Southern Medical University Guangzhou 510515 China

The fabrication of osteochondral tissue engineering scaffolds comprised of different layers is a big challenge. Herein, bilayers comprised of double network hydrogels with or without nano hydroxyapatite （HAp） were developed by exploiting the radical reaction of poly（ethylene glycol） diacrylate （PEGDA） and the Schiff-base reaction of N-carboxyethyl chitosan （CEC） and oxidized hyaluronic acid sodium （OHA） for osteochondral tissue engineering. The bilayered osteochondral scaffold was successfully fabricated based on the superior self-healing property of both hydrogels and evaluated by scanning electron microscopy, macroscopic observation and mechanical measurements. In addition, the hydrogels exhibited good biocompatibility as demonstrated by the in vitro cytotoxicity and in vivo implantation tests. The results indicated that the bilayered hydrogel had great potential for application in osteochondral tissue engineering.

关键词： Bilayered hydrogel Self-healing Osteochondral scaffold Chitosan Hyaluronic acid

Microgel assembly:Fabrication,characteristics and application in tissue engineering and regenerative medicine

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Bioactive Materials 2022年第3期7卷 105-119页

作者： Qi Feng Dingguo Li Qingtao Li xiaodong cao Hua Dong Department of Biomedical Engineering School of Materials Science and EngineeringSouth China University of TechnologyGuangzhouChina National Engineering Research Center for Tissue Restoration and Reconstruction(NERC-TRR) GuangzhouChina Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhouChina Guangdong Province Key Laboratory of Biomedical Engineering South China University of TechnologyGuangzhouChina School of Medicine South China University of TechnologyGuangzhouChina

Microgel assembly,a macroscopic aggregate formed by bottom-up assembly of microgels,is now emerging as prospective biomaterials for applications in tissue engineering and regenerative medicine(TERM).This mini-review first summarizes the fabrication strategies available for microgel assembly,including chemical reaction,physical reaction,cell-cell interaction and external driving force,then highlights its unique characteristics,such as microporosity,injectability and heterogeneity,and finally itemizes its applications in the fields of cell culture,tissue regeneration and biofabrication,especially 3D *** problems to be addressed for further applications of microgel assembly are also discussed.

关键词： Microgel assembly Tissue engineering Regenerative medicine

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

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Bioactive Materials 2024年第10期40卷 460-473页

作者： Zetao Wang Qiyuan Dai Huitong Luo Xiyuan Han Qi Feng xiaodong cao School of Materials Science and Engineering South China University of TechnologyGuangzhou510641PR China National Engineering Research Centre for Tissue Restoration and Reconstruction Guangzhou510006PR China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou510006PR China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou510006PR China Zhongshan Institute of Modern Industrial Technology of SCUT ZhongshanGuangdong528437PR China

Bioactive glasses(BG)play a vital role in angiogenesis and osteogenesis through releasing functional ***,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 *** 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 *** 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 *** 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 *** experiments showed that CuBG-sEVs are favor to cell recruitment,vascularization and osteogenesis as the enrichment of key *** animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to *** findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.

关键词： Copper-doped bioactive glass Extracellular vesicles HIF-1α Bone regeneration

Extracellular vesicles loaded dual-network bioactive sealant via immunoregulation and annulus fibrosus repair for intervertebral disc herniation

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Journal of Materials Science & Technology 2024年第17期184卷 75-87页

作者： Zetao Wang Haofei Li Huitong Luo Hao Wang Zemin Ling Dafu Chen Qi Feng xiaodong cao School of Materials Science and Engineering South China University of TechnologyGuangzhou 510641China National Engineering Research Centre for Tissue Restoration and Reconstruction Guangzhou 510006China School of Medicine South China University of TechnologyGuangzhou 510006China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou 510006China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou 510006China Zhongshan Institute of Modern Industrial Technology of SCUT Guangdong 528437China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spinal SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Laboratory of Bone Tissue Engineering Beijing Laboratory of Biomedical MaterialsBeijing Research Institute of Orthopaedics and TraumatologyBeijing JiShuiTan HospitalBeijing 100035China

Intervertebral disc herniation(IVDH)is a common manifestation of intervertebral disc degeneration(IVDD)characterized by inflammation that results in the rupture of the annulus fibrosus(AF)and her-niation of the nucleus pulposus(NP).While current clinical research primarily focuses on regulating the degenerative NP,the crucial role of the AF in maintaining the mechanical stability and metabolic balance of the intervertebral disc(IVD)has been *** immunoregulation and AF repair is im-perative to effectively prevent recurrent ***,this study introduces a bioactive sealant(OD/GM/QCS-sEVs),which combines gelatin methacryloyl(GM)and oxidized dextran(OD)with quater-nized chitosan(QCS)and incorporates small extracellular vesicles(sEVs).The developed sealant possesses injectability,self-healing capabilities,tissue adhesiveness,and mechanical stability,with an average ad-hesive strength of 109.63 *** vitro experiments demonstrate that OD/GM/QCS-sEVs effectively seal AF defects while preserving mechanical properties comparable to those of a normal ***,the sealant releases sEVs through a pH-responsive mechanism,thereby modulating macrophage polarization to the M2 phenotype via the NF-κB signaling *** mechanism facilitates immunoregulation and anti-inflammatory effects,and promotes stem cell differentiation into *** experiments confirm the ability of OD/GM/QCS-sEVs to seal defects,prevent proteoglycan loss,inhibit IVDD develop-ment,and promote AF ***,OD/GM/QCS-sEVs hold promise as an innovative bioactive sealant for recurrent herniation by resolving immunoregulation and AF regeneration.

关键词： Intervertebral disc herniation Extracellular vesicles Double-network hydrogel Sealant Immunoregulation

Phosphoserine enhanced Cu-doped bioactive glass dynamic dual-network hydrogel for craniofacial bone defect repair

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Regenerative Biomaterials 2023年第1期10卷 1135-1148页

作者： Yuwei Liu Gang Wang Huitong Luo Bangjiao Zhao Muheng Liao Qiyuan Dai Maocai Li Qingtao Li xiaodong cao School of Materials Science and Engineering South China University of TechnologyGuangzhou 510641P.R.China National Engineering Research Centre for Tissue Restoration and Reconstruction Guangzhou 510006P.R.China School of Medicine South China University of TechnologyGuangzhou 510006P.R.China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou 510006P.R.China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou 510006P.R.China Zhongshan Institute of Modern Industrial Technology of SCUT ZhongshanGuangdong 528437P.R.China

Flexible hydrogels containing various osteogenic inorganic constituents,which can accommodate complicated shape variations,are considered as ideal grafts for craniofacial bone defect ***,in most hybrid hydrogels,poor interaction between the polymer network and particles has detrimental effects on hydrogel rheological and structural properties,clinical manipulation and repair *** this article,we designed and prepared a series of hyaluronic acid composite hydrogel containing Cu-doped bioactive glass(CuBG)and phosphoserine(PS),in which hyaluronic acid was modified by methacrylate groups and phenylboronic acid groups to form a double crosslinked *** acted as an interaction bridge of CuBG particles and HAMA-PBA network to improve the mechanical properties of the composite *** CuBG/PS hydrogels exhibited suitable rheological properties(injectable,self-healing,shape-adaptable),bone tissue integrating ability and anti-bacterial ***,we found that CuBG and PS have synergistic effect on improving osteogenic efficiency both in vitro and in vivo,particularly when the ratio of CuBG to PS is lower than 3(9CB/3PS).This work provided a versatile and scalable approach to enhanced the interaction within inorganic particles and polymer network in hydrogels without extra modification on components.

关键词： Cu-doped bioactive glass phosphoserine dynamic hydrogel craniofacial bone defect

Light weight, mechanically strong and biocompatible α-chitin aerogels from different aqueous alkali hydroxide/urea solutions

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Science China Chemistry 2016年第11期59卷 1405-1414页

作者： Beibei Ding Dan Zhao Jianhui Song Huichang Gao Duoduo Xu Min Xu xiaodong cao Lina Zhang Jie Cai College of Chemistry & Molecular Sciences Wuhan University Key Laboratory of Rubber-Plastics Ministry of Education Shandong Provincial Key Laboratory of Rubber-PlasticsQingdao University of Science & Technology Department of Physics Shanghai Key Laboratory of Magnetic Resonance East China Normal University School of Materials Science and Engineering South China University of Technology

Light weight and mechanically strong α-chitin aerogels were fabricated using the sol-gel/self-assembly method from α-chitin in different aqueous alkali hydroxide(KOH, Na OH and Li OH)/urea solutions. All of the α-chitin solutions exhibited temperature-induced rapid gelation behavior. 13 C nuclear magnetic resonance(NMR) spectra revealed that the aqueous alkali hydroxide/urea solutions are non-derivatizing solvents for α-chitin. Fourier transform infrared(FT-IR), X-ray diffraction(XRD) and cross-polarization magic angle spinning(CP/MAS) 13 C NMR confirmed that α-chitin has a stable aggregate structure after undergoing dissolution and regeneration. Subsequently, nanostructured α-chitin aerogels were fabricated by regeneration from the chitin solutions in ethanol and then freeze-drying from t-Bu OH. These α-chitin aerogels exhibited high porosity(87% to 94%), low density(0.09 to 0.19 g/cm^3), high specific surface area(419 to 535 m^2/g) and large pore volume(2.7 to 3.8 cm^3/g). Moreover, the α-chitin aerogels exhibited good mechanical properties under compression and tension models. In vitro studies showed that m BMSCs cultured on chitin hydrogels have good biocompatibility. These nanostructured α-chitin aerogels may be useful for various applications, such as catalyst supports, carbon aerogel precursors and biomedical materials.

关键词： chitin aerogels alkali hydroxide/urea aqueous solutions mechanical properties biocompatibility

A 16-bit 1 MSPS SAR ADC with foreground calibration and residual voltage shift strategy

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Journal of Semiconductors 2020年第12期41卷 41-49页

作者： Xian Zhang xiaodong cao Xuelian Zhang University of Chinese Academy of Sciences Beijing 100049China Institute of Semiconductors Chinese Academy of SciencesBeijing 100083China

In this paper,a 16-bit 1MSPS foreground calibration successive approximation register analog-to-digital converter(SAR ADC)is developed by the CMOS 0.25μm *** on-chip all-digital foreground weights calibration technique integrating self-calibration weight measurement with PN port auto-balance technique is designed to improve the performance and lower the costs of the developed SAR *** SAR ADC has a chip area of 2.7×2.4 mm^2,and consumes only 100μW at the 2.5 V supply voltage with 100 *** INL and DNL are both less than 0.5 LSB.

关键词： foreground all-digital calibration RS strategy RS-based dither auto-zero comparator SAR ADC

Microenvironment responsive nanocomposite hydrogel with NIR photothermal therapy,vascularization and anti-inflammation for diabetic infected wound healing

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Bioactive Materials 2023年第8期26卷 306-320页

作者： Shuangli Zhu Bangjiao Zhao Maocai Li Hao Wang Jiayi Zhu Qingtao Li Huichang Gao Qi Feng xiaodong cao School of Materials Science and Engineering South China University of TechnologyGuangzhou510641PR China National Engineering Research Centre for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou510006PR China School of Medicine South China University of TechnologyGuangzhou510006PR China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou510006PR China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou510006PR China Zhongshan Institute of Modern Industrial Technology of SCUT ZhongshanGuangdong528437PR China

Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic *** present,most of wound repair materials are passive and can’t response to the wound microenvironment,resulting in a low utilization of bioactive substances and hence a poor therapeutic ***,it’s essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of *** this work,metformin-laden CuPDA NPs composite hydrogel(Met@CuPDA NPs/HG)was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine(Gel-DA),Cu-loaded polydopamine nanoparticles(CuPDA NPs)with hyaluronic acid modified by phenyl boronate acid(HA-PBA),which possessed good injectability,self-healing,adhesive and DPPH scavenging *** slow release of metformin was achieved by the interaction with CuPDA NPs,boric groups(B-N coordination)and the constraint of hydrogel *** had a pH and glucose responsive release behavior to treat different wound microenvironment ***,CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of>95%within 10 min and also the slow release of Cu^(2+)to protect wound from infection for a long ***@CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu^(2+).More importantly,Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB *** experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria,inhibiting inflammation,improving angiogenesis and accelerating the deposition of ECM and ***,Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.

关键词： Diabetic ulcer Hydrogel dressing Cu-loaded polydopamine nanoparticles Metformin Photothermal responsiveness Angiogenesis and anti-inflammation