Nanostructured Hydrogel Surfaces for Artificial Extracellular Matrix
用于人工细胞外基质的纳米结构水凝胶表面
基本信息
- 批准号:10373590
- 负责人:
- 金额:$ 18.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-30 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccidentsAddressAdhesionsAdoptedAgingAreaBehaviorBenchmarkingBindingBiologicalCarbohydratesCartilageCell AdhesionCell TransplantationCell surfaceCellsChemical StructureChemicalsChemistryChondrogenesisClinicalCollagenCuesDepositionDifferentiation and GrowthDiseaseElementsEnvironmentExtracellular MatrixFiberFilmFutureGelGenerationsGeometryGoalsHealthHumanHydrogelsHypoxiaImplantIndividualInjuryInstructionLengthLigandsLysineMechanicsMesenchymal Stem CellsModificationModulusMusMyoblastsNanostructuresOrganOrgan TransplantationOsteogenesisPatternPeptidesPerfusionPrintingPropertyRegenerative MedicineResolutionSideSignal TransductionSiteSmooth Muscle MyocytesSpecific qualifier valueStem cell transplantStructureSurfaceSurface PropertiesTechnologyTestingThickThinnessTissuesTransplantationTransplantation SurgeryUnited StatesWaiting Listsangiogenesisbasebiomaterial compatibilitybonecell growthchemical propertydesignexperimental studyflexibilityfunctional lossfunctional restorationimprovedin vivoinnovationlipid biosynthesismechanical propertiesmechanical signalpolyacrylamidepolydiacetylenepolydimethylsiloxanepreventprototyperegenerative tissuerepairedscaffoldstem cell growthstem cellsstemnesssuccesstissue regenerationtissue support frametransplantation therapyvolumetric muscle losswound healing
项目摘要
PROJECT SUMMARY
Scaffolded stem cell transplantation has the potential to provide structured chemical and mechanical cues to
guide cell growth into functional tissues for regenerative medicine. However, significant challenges have limited
the clinical success of this approach. Cells implanted in large scaffolds often have limited viability due to
hypoxic conditions in the host, while cells injected individually or in small clusters often suffer from poor
retention at the site of injury. Hydrogels are commonly utilized as stem cell scaffold materials because they
confer substantial flexibility in terms of chemical composition and ligand integration. However, hydrogels are
also typically amorphous, limiting control over ligand presentation (important for adhesion and signaling), and
lacking structural cues such as fibers that are present in biological ECM, which impacts mechanical strength.
We have recently demonstrated that it is possible to generate stable, 1-nm-resolution functional patterns on
amorphous polyacrylamide and polydimethylsiloxane surfaces, using sub-nm-thick films of highly ordered
polydiacetylenes (PDAs) that are preassembled and covalently transferred to the hydrogel surface. Our
approach potentially addresses both chemical and mechanical challenges associated with hydrogel stem cell
scaffolds, enabling generation of cell-instructive hydrogel tapes that can be shaped to create 3D scaffolds.
However, to be useful in clinical settings, this strategy will need to be validated with: (1) commonly used
hydrogel stem cell scaffold materials, (2) hydrogel moduli matching the range commonly associated with
tissues, and (3) films thin enough for adequate perfusion to prevent hypoxia and enable normal secretome
interactions. Here, we develop a platform technology based on cell-instructive hydrogel tapes, benchmarking
their chemical and mechanical properties, and their impacts on human mesenchymal stem cells (hMSCs).
In Aim 1, we evaluate the hypothesis that PDA surface functionalization can improve chemical control over
surfaces of hydrogels common in regenerative medicine, orienting and spatially clustering ligand presentation,
to modify stem cell growth in a predictable fashion. We test this by culturing hMSCs on surfaces designed to
maintain stemness or to induce specified differentiation behavior (angiogenesis, adipogenesis,
chondrogenesis), benchmarking against common stochastic hydrogel modification strategies.
In Aim 2, we evaluate the hypothesis that our PDA surface-functionalization approach can improve the
mechanical and handling properties of thin, soft hydrogel films, enabling creation of cell-instructive hydrogel
tapes. We generate and test impacts of paired tapes as cell sandwich scaffolds and 3D constructs that provide
structured chemical surfaces and mechanical environments, while maximizing perfusion to and from cells.
Overall, this proposal develops a modular surface functionalization strategy that can be easily integrated with
many existing hydrogels for tissue scaffolds, providing structured ligand presentation and mechanical strength
aimed at improving utility in clinical cell transplantation therapies.
项目总结
支架干细胞移植有可能提供结构化的化学和机械线索
引导细胞向功能组织生长,用于再生医学。然而,重大挑战有限。
这种方法在临床上的成功。移植到大型支架中的细胞通常由于
宿主的低氧条件,而单独注射或以小簇形式注射的细胞往往表现不佳
在受伤部位滞留。水凝胶通常被用作干细胞支架材料,因为它们
在化学组成和配体集成方面赋予了相当大的灵活性。然而,水凝胶是
通常也是无定形的,限制了对配体呈递的控制(对于粘合和信号传递很重要),以及
缺乏结构线索,如生物ECM中存在的纤维,这会影响机械强度。
我们最近已经证明,有可能在上产生稳定的1 nm分辨率的功能图案
无定形聚丙烯酰胺和聚二甲基硅氧烷表面,使用高度有序的亚纳米厚的薄膜
预组装并共价转移到水凝胶表面的聚二乙炔(PDA)。我们的
该方法潜在地解决了与水凝胶干细胞相关的化学和机械挑战
支架,能够产生细胞指导性水凝胶带,可以成形以创建3D支架。
然而,为了在临床环境中有用,这一策略将需要通过:(1)常用的
水凝胶干细胞支架材料,(2)水凝胶模数与通常相关的范围相匹配
组织,以及(3)足够薄的薄膜,足以防止缺氧和正常分泌
互动。在这里,我们开发了一种基于细胞的平台技术-水凝胶胶带,标杆
它们的化学和机械特性,以及它们对人骨髓间充质干细胞(HMSCs)的影响。
在目标1中,我们评估了pda表面功能化可以改善化学控制的假设。
再生医学中常见的水凝胶表面,定向和空间聚集配体呈现,
以可预测的方式改变干细胞的生长。我们通过培养hMSCs来测试这一点
维持茎或诱导特定的分化行为(血管生成、脂肪生成、
软骨形成),对照常见的随机水凝胶修饰策略。
在目标2中,我们评估了我们的PDA表面功能化方法可以改善
薄薄、柔软的水凝胶膜的机械和操作性能,使创建细胞指导型水凝胶成为可能
录像带。我们生成并测试成对胶带作为细胞夹层支架和3D结构的影响,这些结构提供了
结构化的化学表面和机械环境,同时最大限度地向细胞和从细胞灌流。
总体而言,该提案开发了一种模块化表面功能化策略,可以很容易地与
许多现有的用于组织支架的水凝胶,提供结构化的配体呈现和机械强度
旨在提高临床细胞移植治疗的实用性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Shelley Ann Claridge其他文献
Shelley Ann Claridge的其他文献
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{{ truncateString('Shelley Ann Claridge', 18)}}的其他基金
Nanostructured Hydrogel Surfaces for Artificial Extracellular Matrix
用于人工细胞外基质的纳米结构水凝胶表面
- 批准号:
10705022 - 财政年份:2022
- 资助金额:
$ 18.4万 - 项目类别:
Single-Molecule Scanning Tunneling Spectroscopy of Surface-Tethered Proteins
表面束缚蛋白的单分子扫描隧道光谱
- 批准号:
7928338 - 财政年份:2009
- 资助金额:
$ 18.4万 - 项目类别:
Single-Molecule Scanning Tunneling Spectroscopy of Surface-Tethered Proteins
表面束缚蛋白的单分子扫描隧道光谱
- 批准号:
7991338 - 财政年份:2009
- 资助金额:
$ 18.4万 - 项目类别:
Single-Molecule Scanning Tunneling Spectroscopy of Surface-Tethered Proteins
表面束缚蛋白的单分子扫描隧道光谱
- 批准号:
8146179 - 财政年份:2009
- 资助金额:
$ 18.4万 - 项目类别:
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