In Situ Bioconjugation as a Therapeutic Delivery Modality to Enhance Ocular Wound Healing

原位生物共轭作为增强眼部伤口愈合的治疗传递方式

• 批准号: 10171858
• 负责人: David Myung
• 金额: $ 22.3万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171858
• 关键词: Adhesions; Alkynes; Animal Model; Award; Azides; Biocompatible Materials; Biological; Biological Assay; Biomedical Engineering; Blood Circulation; Burn injury; Cell Survival; Cells; Chemical Injury; Chemistry; Cicatrix; Clinical; Collagen; Complex; Confocal Microscopy; Consult; Copper; Cornea; Corneal Injury; Corneal Stroma; Coupled; Debridement; Disease; Doctor of Philosophy; Encapsulated; Engineering; Epidermal Growth Factor; Epithelial; Esters; Eye; Eye Burns; FDA approved; Fostering; Foundations; Future; Gel; Goals; Growth; Growth Factor; Human; Hybrids; Immobilization; Immunohistochemistry; Impaired healing; Impairment; In Situ; In Vitro; Infection; Injectable; Injections; Institutes; Ions; K-Series Research Career Programs; Laboratories; Lead; Materials Testing; Mechanics; Membrane; Mentorship; Mesenchymal Stem Cells; Metals; Modality; National Eye Institute; Natural regeneration; Nerve; Nerve Growth Factors; Nerve Regeneration; Operative Surgical Procedures; Ophthalmology; Perforation; Phenotype; Polyethylene Glycols; Process; Proteins; Regenerative Medicine; Regenerative capacity; Regenerative research; Research; Research Personnel; Research Priority; Role; Schools; Specialist; Stem cell transplant; Surface Plasmon Resonance; Suspensions; Techniques; Testing; Therapeutic; Tissue Engineering; Tissues; Topical application; Traumatic injury; Ulcer; Ultraviolet Rays; Western Blotting; arm; biomaterial compatibility; catalyst; chemical binding; corneal epithelial wound healing; crosslink; cycloaddition; epithelial wound; epithelium regeneration; extracellular; healing; improved outcome; mechanical properties; melting; neurotransmission; ocular surface; prevent; professor; response; skills; stem cells; wound; wound bed; wound healing

ABSTRACT This is a K08 award application submitted by David Myung, MD, PhD, who is being hired as an Assistant Professor of Ophthalmology at the Byers Eye Institute at Stanford. Dr. Myung is establishing himself as an investigator in translational bioengineering research focused on corneal wound healing. The K08 award will provide Dr. Myung with the support necessary to further develop specific expertise in corneal wound healing and regenerative medicine, and to acquire the skills necessary to become an independent investigator. To help him achieve these goals, Dr. Myung has assembled an interdisciplinary mentorship team comprised of the following leading investigators in their fields: Dr. Ali Djalilian is an expert in corneal wound healing, and in particular ocular surface disease and stem cell transplantation; Dr. Sarah Heilshorn is an expert in biomaterials; Dr. Jeffrey Goldberg is an expert in nerve regeneration. In addition, he will consult with Dr. Edward Manche from Stanford, a clinical cornea specialist with expertise in corneal crosslinking chemistry, Dr. Christopher Murphy from UC Davis, an expert in testing growth factors in animal models of corneal wound healing, as well as Dr. Jeffrey Tok, who directs the soft and hybrid materials testing facility at Stanford's School of Engineering. In the treatment of traumatic injuries, ulcers, and burns of the eye, inadequate tissue healing remains a major challenge. The cornea is particularly vulnerable to the blinding consequences of delayed healing such as scarring, melts, and perforations. There is, therefore, a major clinical need for new ways to enhance wound healing in the eye. This research investigates the benefits of using highly cell-friendly bioconjugation chemistries to deliver therapeutic factors directly to wounded corneal tissue in three ways: (1) through an injectable gel that covers wounds and releases growth factors, (2) by chemically binding growth factors directly to the wound bed, and (3) by encapsulating human mesenchymal stem cells (hMSCs) within a gel at the ocular surface. The first aim is to characterize and control corneal re- epithelialization through growth-factor eluting collagen gels formed on wounds in situ. The second aim is to evaluate and optimize the epithelial and nerve regeneration effects of growth factors coupled directly to a nerve-ablated cornea. The third aim is to elucidate and maximize the bioactivity of hMSCs encapsulated within collagen gels on a chemically-injured ocular surface. This research may lead to new corneal wound healing therapies that overcome the limitations of topically delivered growth factors and stem cells, and will form the basis of an R01 application before the end of the K award.

摘要 这是一份由大卫明博士提交的K 08奖申请，他被聘为 斯坦福大学拜尔斯眼科研究所眼科学助理教授。明医生正在建立 他本人是转化生物工程研究的研究员，专注于角膜伤口愈合。 K 08奖将为Myung博士提供进一步发展特定专业知识所需的支持 在角膜伤口愈合和再生医学，并获得必要的技能，成为一个 独立调查员为了帮助他实现这些目标，Myung博士收集了一份 跨学科导师团队由以下领域的主要研究人员组成：阿里博士 Djalilian是角膜伤口愈合的专家，特别是眼表疾病和干细胞 移植;莎拉·海尔斯霍恩博士是生物材料方面的专家;杰弗里·戈德堡博士是生物材料方面的专家。 神经再生此外，他还将咨询来自斯坦福大学的爱德华·曼奇博士， 具有角膜交联化学专业知识的角膜专家，来自UC的Christopher Murphy博士 戴维斯博士是在角膜伤口愈合的动物模型中测试生长因子的专家。 杰弗里·托克（Jeffrey Tok）是斯坦福大学物理学院软质和混合材料测试设施的负责人。 工程. 在眼外伤、溃疡和烧伤的治疗中，组织愈合不充分仍然是一个问题。 重大挑战。角膜特别容易受到延迟愈合的致盲后果的影响 例如疤痕、熔化和穿孔。因此，临床上需要新的方法来 促进眼睛的伤口愈合。这项研究调查了使用高度细胞友好的 生物结合化学将治疗因子直接递送到三种不同的创伤角膜组织， 方法：（1）通过注射凝胶覆盖伤口并释放生长因子，（2）通过化学方法 将生长因子直接结合到伤口床，和（3）通过包封人间充质干细胞 细胞（hMSC）在眼表面的凝胶内。第一个目标是表征和控制角膜再狭窄， 通过生长因子洗脱的胶原凝胶在伤口上原位形成的上皮形成。第二个目的 是评估和优化上皮和神经再生的影响，生长因子耦合 直接移植到切除了神经的角膜上第三个目的是阐明和最大化hMSCs的生物活性 包封在化学损伤的眼表面上的胶原凝胶内。这项研究可能会导致 克服局部递送生长因子的局限性的新的角膜伤口愈合疗法 和干细胞，并将形成在K奖结束前的R 01申请的基础。