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Engineering microparticles based on solidified stem cell secretome with an augmented pro-angiogenic factor portfolio for therapeutic angiogenesis

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Bioactive Materials 2022年第11期7卷 526-541页

作者： Thomas Spater Marisa Assunçao Kwok Keung Lit Guidong Gong Xiaoling Wang Yi-Yun Chen Ying Rao Yucong Li Chi Him Kendrick Yiu Matthias W.Laschke michael D.Menger Dan Wang Rocky S.Tuan Kay-Hooi Khoo michael raghunath Junling Guo Anna Blocki Institute for Clinical&Experimental Surgery Saarland UniversityHomburgSaarGermany School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong KongChina Institute for Tissue Engineering and Regenerative Medicine The Chinese University of Hong KongShatinNew TerritoriesHong KongChina BMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and EngineeringSichuan UniversityChengduSichuan610065China Bioproducts Institute Departments of Chemical and Biological EngineeringThe University of British ColumbiaVancouverBCCanada Academia Sinica Common Mass Spectrometry Facilities for Proteomics and Protein Modification Analysis and Institute of Biological ChemistryAcademia SinicaNankangTaipeiChina Shun Hing Institute of Advanced Engineering(SHIAE) Faculty of EngineeringThe Chinese University of Hong KongShatinNew TerritoriesHong KongChina Ministry of Education Key Laboratory for Regenerative Medicine School of Biomedical SciencesThe Chinese University of Hong KongShatinNew TerritoriesHong KongChina Department of Orthopaedics&Traumatology The Chinese University of Hong KongShatinNew TerritoriesHong KongHong Kong Special Administrative Region of China Institute for Chemistry and Biotechnology Zurich University of Applied SciencesWadenswilSwitzerland State Key Laboratory of Polymer Materials Engineering Sichuan UniversityChengduSichuan610065China

Tissue (re)vascularization strategies face various challenges, as therapeutic cells do not survive long enough in situ, while the administration of pro-angiogenic factors is hampered by fast clearance and insufficient ability to emulate complex spatiotemporal signaling. Here, we propose to address these limitations by engineering a functional biomaterial capable of capturing and concentrating the pro-angiogenic activities of mesenchymal stem cells (MSCs). In particular, dextran sulfate, a high molecular weight sulfated glucose polymer, supplemented to MSC cul-tures, interacts with MSC-derived extracellular matrix (ECM) components and facilitates their co-assembly and accumulation in the pericellular space. Upon decellularization, the resulting dextran sulfate-ECM hybrid material can be processed into MIcroparticles of SOlidified Secretome (MIPSOS). The insoluble format of MIPSOS protects protein components from degradation, while facilitating their sustained release. Proteomic analysis demonstrates that MIPSOS are highly enriched in pro-angiogenic factors, resulting in an enhanced pro-angiogenic bioactivity when compared to naïve MSC-derived ECM (cECM). Consequently, intravital microscopy of full-thickness skin wounds treated with MIPSOS demonstrates accelerated revascularization and healing, far superior to the ther-apeutic potential of cECM. Hence, the microparticle-based solidified stem cell secretome provides a promising platform to address major limitations of current therapeutic angiogenesis approaches.

关键词： Dextran sulfate Extracellular matrix Mesenchymal stem cells Therapeutic angiogenesis Wound healing Poly-electrolyte-driven co-assembly

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Effects of nanotopography on stem cell phenotypes

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World Journal of Stem Cells 2009年第1期1卷 55-66页

作者： Rajeswari Ravichandran Clarisse CH Ng Casey K Chan michael raghunath Seeram Ramakrishna Division of Bioengineering Faculty of EngineeringNational University of SingaporeSingapore 117574Singapore Department of Mechanical Engineering Faculty of Engineering National University of SingaporeSingapore 117576Singapore Nanoscience and Nanotechnology Initiative National University of Singapore2 Engineering Drive 3Singapore 117576Singapore Department of Restorative Dentistry Faculty of DentistryNational University of SingaporeSingapore 119074 Singapore Department of Orthopaedic Surgery Yong Loo Lin School of MedicineNational University of Singapore Singapore 119074Singapore Department of Biochemistry Yong Loo Lin School of Medicine8 Medical DriveNational University of SingaporeSingapore 117597Singapore

Stem cells are unspecialized cells that can self renew indefinitely and differentiate into several somatic cells given the correct environmental *** the stem cell niche,stem cell-extracellular matrix(ECM)interactions are crucial for different cellular functions,such as adhesion,proliferation,and ***, in addition to chemical surface modifications,the importance of nanometric scale surface topography and roughness of biomaterials has increasingly becoming recognized as a crucial factor for cell survival and host tissue acceptance in synthetic *** review describes the influence of nanotopography on stem cell phenotypes.

关键词： Stem cells Nanofibers Nanotopography Biomaterials Extracellular matrix Differentiation

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