Generation of suturable artificial cornea from the integration of exfoliated graphene with gelatin glycidyl methacrylate

通过剥离石墨烯与明胶甲基丙烯酸缩水甘油酯的整合生成可缝合的人工角膜

• 批准号: 9976013
• 负责人: Sina SHARIFI
• 金额: $ 10.27万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9976013
• 关键词: 3-Dimensional; Adhesives; Anatomy; Animal Model; Animals; Architecture; Artificial Implants; Automobile Driving; Award; Biocompatible Materials; Biological; Biomechanics; Biomedical Engineering; Biomimetics; Blindness; Cell Communication; Cell Differentiation process; Cell Proliferation; Cells; Characteristics; Clinical; Communities; Complement; Cornea; Cultured Cells; Data Analyses; Development; Differentiation and Growth; Diffusion; Donor person; Endothelial Cells; Endothelium; Engineering; Epithelial; Epithelium; Extracellular Matrix; Eye; Fibroblasts; Functional disorder; Funding; Gelatin; Generations; Glucose; Glues; Goals; Grant; Human; Hybrids; Hydrogels; Immune response; In Vitro; Infection; Keratoplasty; Laboratories; Lead; Manuscripts; Mechanics; Membrane; Mentors; Microspheres; Molecular; Molecular and Cellular Biology; Natural graphite; Nature; Nerve Regeneration; Normal Cell; Operative Surgical Procedures; Organic solvent product; Oryctolagus cuniculus; Oxygen; Patients; Pattern; Phase; Polymers; Postoperative Care; Process; Property; Proteins; Quality of life; Research; Research Proposals; Scientist; Solubility; Solvents; Stress; Stromal Cells; Structure; Supporting Cell; Surgical sutures; System; Techniques; Tissue Engineering; Tissue Preservation; Tissues; Training; Transplantation; Treatment Cost; United States National Institutes of Health; Writing; Xenograft procedure; aqueous; base; biomaterial compatibility; blind; career; cell motility; cell stroma; chemical property; crosslink; design; experimental study; faculty research; falls; glycidyl methacrylate; graphene; healing; implantation; improved; in vivo; in vivo Model; infancy; leadership development; materials science; mechanical properties; migration; multidisciplinary; nano; notch protein; preservation; scaffold; skills; stem; success; three-dimensional modeling

PROJECT SUMMARY     In  this  project,  we  propose  to  design  a  hybrid  scaffold  from  the  integration  of  gelatin  glycidyl  methacrylate  (GELGYM)  with  exfoliated  pristine  graphene  (EG),  accompanied  by  double  crosslinking  technique,  that  can  function as a suturable artificial cornea. We will determine (1) whether hybrid GELGYM membranes acts as a  biocompatible  artificial  cornea  that  supports  cell  growth  and  differentiation;;  and  (2)  the  capability  of  the  hybrid  scaffold  to  function  as  a  corneal  substitute.  The  differentiation  and  biocompatibility  studies  proposed  here  will  offer  quantitative  information  on  the  degree  of  biointegration  of  the  hybrid  scaffold  in  contact  with  the  host’s  corneal cells and extracellular matrix under in vitro and in vivo conditions.     We expect that exfoliation of graphene, its integration in the GELGYM hydrogel architecture and subsequent  double crosslinking can create an nano-­microspherical cavities in the hydrogel microstructure covered with the  graphene  create  anchoring  points  that  can  withstand  against  tearing,  after  applying  the  physical  stress  to  the  suture passing the construct. This can diminish the tendency to form notches during suturing, while enhancing  mechanical  properties  of  the  construct  and  facilitate  its  implantation  in  patients.  Moreover,  we  expect  integration  will  further  promote  cell  proliferation  and  differentiation  of  corneal  cells,  allowing  for  the appropriate  diffusion  of  glucose  and  oxygen.  Additionally,  I  anticipate  that  integration  of  exfoliated  graphene  will  positively  regulate  epithelial-­stromal  and  endothelial  stromal  cell  interactions.  The  success  of  this  approach  can  reduce  or eliminate the need for donor corneas and positively impact the quality of life for many patients.     The  research  aims  are  supported  by  a  training  plan  focused  on  the  acquisition  of  relevant  multidisciplinary  expertise  in  the  fields  of  cellular  and  molecular  biology,  pathophysiology,  tissue-­engineering  and  material  science. To this end, a “Mentoring Team” which includes the leading mentor, Dr. Chodosh, along with two co-­ mentors:  Dr.  Gonzalez  and  Dr.  Kong  has  been  assembled.  Moreover,  Dr.  Paschalis  as  an  independent  collaborator  will  support  on  technical  training  on  animal  handling,  surgery,  and  postoperative  care  along  with  data analysis and interpretation of animal findings following implantation of the scaffold into rabbit eyes.     This  group  of  mentors  will  guide  me  during  the  K99  mentored  phase  to  achieve  my long-­term  career  goal  of  becoming  a  scientist-­leader  in  my  field  with  a  strong  independent  laboratory.  I  envision  that  this  award  will  provide  me  with  an  excellent  platform  from  which  to  have  a  successful  transition  to  independent  research  faculty status (this includes the transition into the R00 phase of the award) and in the long term, to productively  compete  for  independent  NIH  (R01)  funding.  My  training  will  also  be  complemented  by  courses  during  the  mentored  phase  in  the  improvement  of  presentation  and  writing  skills  (grants  and  manuscripts),  manuscript  review, mentoring, and development of leadership abilities and laboratory management skills.

项目总结