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Tailoring minimalist self-assembling peptides for localized viral vector aene deliverv

Nano Research 2016年第3期9卷 674-684页

作者： Alexandra L. Rodriguez Ting-Yi Wang Kiara F. Bruggeman Rui Li Richard J. Williams Clare L. Parish David R. Nisbet Research School of Engineering The Australian National University Canberra ACT2601 Australia Florey Institute ofNeuroscience & Men tal Health The University of Melbourne Parkville VIC 3010 Australia Cen tre for Chemistry and Biotechnology Deakin University Waurn Ponds VIC 3217 Australia School of Aerospace Mechanical and Manufacturing Engineering and the Health Innovations Research Institute RMIT University Melbourne VIC 300 I Australia

Viral vector gene delivery is a promising technique for the therapeutic administra- tion of proteins to damaged tissue for the improvement of regeneration outcomes in various disease settings including brain and spinal cord injury, as well as autoimmune diseases. Though promising results have been demonstrated, limitations of viral vectors, including spread of the virus to distant sites, neutralization by the host immune system, and low transduction efficiencies have stimulated the investigation of biomaterials as gene delivery vehicles for improved protein expression at an injury site. Here, we show how N- fluorenylmethyloxycarbonyl （Fmoc） self-assembling peptide （SAP） hydrogels, designed for tissue-specific central nervous system （CNS） applications via incorporation of the laminin peptide sequence isoleucine-lysine-valine-alanine- valine （IKVAV）, are effective as biocompatible, localized viral vector gene delivery vehicles in vivo. Through the addition of a C-terminal lysine （K） residue, we show that increased electrostatic interactions, provided by the additional amine side chain, allow effective immobilization of lentiviral vector particles, thereby limiting their activity exclusively to the site of injection and enabling focal gene delivery in vivo in a tissue-specific manner. When the C-terminal lysine was absent, no difference was observed between the number of transfected cells, the volume of tissue transfected, or the transfection efficiency with and without the Fmoc-SAP. Importantly, immobilization of the virus only affected transfection cell number and volume, with no impact observed on transfection efficiency. This hydrogel allows the sustained and targeted delivery of growth factors post injury. We have established Fmoc-SAPs as a versatile platform for enhanced biomaterial design for a range of tissue engineering applications.

关键词： viral vectors gene therapy self-assembling peptides biomaterials

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Patterning the neuronal cells via inkjet printing of self-assembled peptides on silk scaffolds

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Progress in Natural Science:Materials International 2020年第5期30卷 686-696页

作者： Weizhen Sun Yi Zhang David A.Gregory Ana Jimenez-Franco Mhd Anas Tomeh Songwei Lv Jiqian Wang John W.Haycock Jian R.Lu Xiubo Zhao Department of Chemical and Biological Engineering University of Sheffield Department of Materials Science & Engineering University of Sheffield School of Pharmacy Changzhou University Centre for Bioengineering and Biotechnology China University of Petroleum East China School of Physics and Astronomy University of Manchester

The patterning of neuronal cells and guiding neurite growth are important for neuron tissue engineering and cell-based biosensors. In this paper, inkjet printing has been employed to pattern self-assembled I3QGK peptide nanofibers on silk substrates for guiding the growth of neuron-like PC12 cells. Atomic force microscopy(AFM)confirmed the dynamic self-assembly of I3QGK into nanofiber structures. The printed self-assembled peptide strongly adheres to regenerated silk fibroin(RSF) substrates through charge-charge interactions. It was observed that in the absence of I3QGK, PC12 cells exhibited poor attachment to RSF films, while for RSF surfaces coated or printed with peptide nanofibers, cellular attachment was significantly improved in terms of both cell density and morphology. AFM results revealed that peptide nanofibers can promote the generation of axons and terminal buttons of PC12 cells, indicating that I3QGK nanofibers not only promote cellular attachment but also facilitate differentiation into neuronal phenotypes. Inkjet printing allows complex patterning of peptide nanofibers onto RSF substrates, which enabled us to engineer cell alignment and provide an opportunity to direct axonal development in vitro. The live/dead assay showed that printed I3QGK patterns exhibit no cytotoxicity to PC12 cells demonstrating potential for future nerve tissue engineering applications.

关键词： Neurobiology Micro-patterning Inkjet printing self-assembling peptides PC12 cells

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Aligned fibrin/functionalized self-assembling peptide interpenetrating nanofiber hydrogel presenting multi-cues promotes peripheral nerve functional recovery

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Bioactive Materials 2022年第2期7卷 529-544页

作者： Shuhui Yang Jinjin Zhu Changfeng Lu Yi Chai Zheng Cao Jiaju Lu Zhe Zhang He Zhao Yin-Yuan Huang Shenglian Yao Xiangdong Kong Peixun Zhang Xiumei Wang State Key Laboratory of New Ceramics and Fine Processing Key Laboratory of Advanced Materials of Ministry of EducationSchool of Materials Science and EngineeringTsinghua UniversityBeijing100084PR China Key Laboratory of Trauma and Neural Regeneration Peking UniversityMinistry of EducationDepartment of Trauma and OrthopedicsPeking University People’s HospitalBeijing100044PR China Department of Orthopaedic Surgery Sir Run Run Shaw HospitalZhejiang University School of Medicine&Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of ZhejiangHangzhou310016PR China School of Clinical Medicine Tsinghua UniversityBeijing100084PR China School of Materials Science and Engineering University of Science and Technology BeijingBeijing100083PR China School of Materials Science and Engineering Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue EngineeringZhejiang Sci-Tech UniversityHangzhou310018PR China

Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects(15 mm in rats and 25 mm in humans),which can be improved by a beneficial intraluminal ***,individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal ***,an aligned fibrin/functionalized self-assembling peptide(AFG/fSAP)interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular *** hydrogel possesses an aligned structure,high water content,appropriate mechanical properties and suitable biodegradation capabilities for nerve repair,which enhances the alignment and neurotrophin secretion of primary Schwann cells(SCs)in vitro,and successfully bridges a 15-mm sciatic nerve gap in rats in *** rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated *** motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of ***,the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated ***,the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation.

关键词： Peripheral nerve regeneration Alignment Nanofibers Fibrin self-assembling peptides

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