CAREER: Determining the structure and properties of cell re-engineered microenvironments using rheology in synthetic wound healing scaffolds

职业:利用合成伤口愈合支架的流变学确定细胞重新设计的微环境的结构和特性

基本信息

  • 批准号:
    1751057
  • 负责人:
  • 金额:
    $ 50万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-03-01 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

Human mesenchymal stem cells (hMSCs) play a critical role in wound healing by regulating inflammation after migrating to the wound site. One strategy to help wound healing is to implant a hydrogel containing isolated hMSCs directly into the wound site. The hydrogel provides structural integrity to the surrounding tissue. However, during wound healing, hMSCs remodel and degrade the hydrogel over time. These processes must be better understood to design hydrogels with the optimal properties for wound healing. This CAREER project will apply a combination of new and existing methods to characterize the region around cells during cell remodeling and degradation of the synthetic hydrogel material. The goal of the combined research and education effort is to: (1) use a novel interdisciplinary approach to provide new techniques to answer a critical problem in biomaterials and cell biology, (2) recruit and train a diverse work force and (3) educate a broad audience in biomaterials, materials characterization, and wound healing. The research will have a major impact on biomaterials design. These new materials have the potential to increase the rate of wound healing and prevent development of chronic wounds. In addition, the principle investigator will recruit, train and educate a broad audience. This will be done by: (i) outreach to the public at the Da Vinci Science Center in Allentown, PA, (ii) mentoring of middle and high school students and (iii) mentoring and training of undergraduate and graduate students.The overall goal of this work is to characterize the spatial and temporal rheological evolution of a synthetic hydrogel during cell-mediated degradation to determine viability as an implantable wound healing scaffold. The physical microenvironment is hypothesized to control hMSC degradation strategies during cell migration to efficiently deliver hMSCs to the wound and control material degradation. To test this, the research includes a) characterizing hMSC degradation strategies in homogenous hydrogels that mimic the stiffness of native tissues, b) determining the change in response to an interface in stiffness, and c) determining how gradients in scaffold stiffness change hMSC-mediated degradation and direct motility to increase cell delivery and material integrity. hMSCs will be encapsulated in 3D in a well-established photopolymerizable poly(ethylene glycol)-peptide hydrogel. The peptide cross-linker in this material is degraded by cell-secreted enzymes. Dynamic scaffold properties will be measured with bulk rheology and microrheology. Multiple particle tracking microrheology (MPT) will measure the spatio-temporal degradation profile created in the scaffold by encapsulated hMSCs. These measurements will determine the unique degradation strategies hMSCs use in response to changes in their microenvironment. Bulk rheology will quantify the change in material integrity as hMSCs permanently degrade the synthetic scaffold. Using this knowledge, the viability of these materials as implantable wound healing scaffolds and the microenvironments that most efficiently deliver hMSCs to an injury while providing structure to the surrounding tissue will be determined. The research outcomes will be: i) identification of the microenvironment cells engineer during motility in response to homogeneous and heterogeneous environments in the scaffold and ii) determination of microenvironments that increase cell delivery and material integrity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
人间充质干细胞(HMSC)在迁移到伤口部位后调节炎症在伤口愈合中起关键作用。 帮助伤口愈合的一种策略是将含有孤立的HMSC的水凝胶直接植入伤口部位。 水凝胶为周围组织提供结构完整性。 但是,在伤口愈合过程中,HMSC随着时间的推移重塑并降解水凝胶。 必须更好地理解这些过程,以设计具有伤口愈合的最佳特性的水凝胶。该职业项目将采用新的和现有方法的组合来表征合成水凝胶材料的细胞重塑和降解过程中细胞周围区域的表征。 (1)使用一种新型的跨学科方法来提供新技术来回答生物材料和细胞生物学中的关键问题,(2)招募和培训多样化的劳动力,(3)对生物材料,材料表征和伤口愈合的广泛受众教育。该研究将对生物材料设计产生重大影响。这些新材料有可能提高伤口愈合率并防止慢性伤口的发展。此外,主要调查员将招募,培训和教育广泛的受众。这将通过:(i)在宾夕法尼亚州阿伦敦的达芬奇科学中心向公众推广,(ii)指导中学生和(iii)指导和培训本科生和研究生的指导和培训。这项工作的总体目标是表征在细胞介导的疗程中,可以通过愈合的疾病来促进疾病的空间和暂时性流氓进化,以通过抚养性地促进了一项努力。假设物理微环境可以控制细胞迁移过程中的HMSC降解策略,以有效地将HMSC递送到伤口并控制材料降解。为了进行测试,研究包括a)表征模仿天然组织刚度的同质水凝胶中的HMSC降解策略,b)确定响应于刚度的界面的变化,c)确定脚手架刚度中的梯度如何改变HMSC介导的降解和引导性的降解和引导性,以增加细胞递送和材料整​​合性。 HMSC将封装在3D中,在良好的光聚合聚(乙二醇) - 肽水凝胶中。该材料中的肽交联链被细胞分泌的酶降解。动态脚手架特性将以散装的流变学和微流性测量。多个粒子跟踪微流变学(MPT)将测量由封装的HMSC在支架中创建的时空降解曲线。这些测量结果将确定HMSC用于响应其微环境变化的独特降解策略。随着HMSC永久降解合成支架,大量流变学将量化材料完整性的变化。利用这些知识,将确定这些材料作为可植入的伤口愈合支架和最有效地将HMSC损伤带到损伤的微环境的微环境的可行性。 The research outcomes will be: i) identification of the microenvironment cells engineer during motility in response to homogeneous and heterogeneous environments in the scaffold and ii) determination of microenvironments that increase cell delivery and material integrity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Chemical engineering ‘on-a-chip’: Capturing the integrated scope of chemical engineering through STEM outreach
化学工程“片上”:通过 STEM 推广了解化学工程的综合范围
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Schultz, Kelly M.;Snyder, Mark A.
  • 通讯作者:
    Snyder, Mark A.
Characterizing Nonuniform Hydrogel Elastic Moduli Using Autofluorescence
使用自发荧光表征不均匀水凝胶弹性模量
  • DOI:
    10.1021/acs.macromol.2c00241
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    5.5
  • 作者:
    McGlynn, John A.;Schultz, Kelly M.
  • 通讯作者:
    Schultz, Kelly M.
Multiple particle tracking microrheological characterization: Fundamentals, emerging techniques and applications
  • DOI:
    10.1063/5.0006122
  • 发表时间:
    2020-05-29
  • 期刊:
  • 影响因子:
    3.2
  • 作者:
    McGlynn, John A.;Wu, Nan;Schultz, Kelly M.
  • 通讯作者:
    Schultz, Kelly M.
Multiple particle tracking microrheology measured using bi-disperse probe diameters
使用双分散探针直径测量多粒子跟踪微流变学
  • DOI:
    10.1039/c8sm01098f
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Wehrman, Matthew D.;Lindberg, Seth;Schultz, Kelly M.
  • 通讯作者:
    Schultz, Kelly M.
Measuring human mesenchymal stem cell remodeling in hydrogels with a step-change in elastic modulus
通过弹性模量的阶跃变化测量水凝胶中人间充质干细胞的重塑
  • DOI:
    10.1039/d2sm00717g
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    McGlynn, John A.;Schultz, Kelly M.
  • 通讯作者:
    Schultz, Kelly M.
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Kelly Schultz其他文献

Kelly Schultz的其他文献

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{{ truncateString('Kelly Schultz', 18)}}的其他基金

GOALI: Determination of the Structure and Properties of Microfibrillated Cellulose during Dynamic Phase Transitions
目标:动态相变期间微原纤化纤维素的结构和性能的测定
  • 批准号:
    1933251
  • 财政年份:
    2019
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant

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基于微结构抛光头的小口径非球面光学模具磁场增强力流变确定性抛光
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运载火箭箭体结构跨尺度不确定性传播分析与设计
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