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 functionasasuturableartificialcornea.Wewilldetermine(1)whetherhybridGELGYMmembranesactsasa 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 cornealcellsandextracellularmatrixunderinvitroandinvivoconditions. Weexpectthatexfoliationofgraphene,itsintegrationintheGELGYMhydrogelarchitectureandsubsequent doublecrosslinkingcancreateannano-microsphericalcavitiesinthehydrogelmicrostructurecoveredwiththe graphene create anchoring points that can withstand against tearing, after applying the physical stress to the suturepassingtheconstruct.Thiscandiminishthetendencytoformnotchesduringsuturing,whileenhancing 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 theappropriate 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 oreliminatetheneedfordonorcorneasandpositivelyimpactthequalityoflifeformanypatients.
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.Tothisend,a?MentoringTeam?whichincludestheleadingmentor,Dr.Chodosh,alongwithtwoco- 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 dataanalysisandinterpretationofanimalfindingsfollowingimplantationofthescaffoldintorabbiteyes. This group of mentors will guide me during the K99 mentored phase to achieve mylong-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 facultystatus(thisincludesthetransitionintotheR00phaseoftheaward)andinthelongterm,toproductively 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,anddevelopmentofleadershipabilitiesandlaboratorymanagementskills.
Cornealtransplantationcurrentlyrepresentstheprimarytreatmentforcornealblindness,yetseverescarcityof donor corneas in the global prospect, tissue suitability for transplantation, donor-derived infections, along with the cost of treatment and preservation are the main challenges driving the scientific community to find new solutions. In this research proposal, I aim to design a hybrid scaffold from the integration of gelatin glycidyl methacrylate(GELGYM)withexfoliatedpristinegraphene,accompaniedbydoublecrosslinkingtechnique,that canfunctionasansuturableartificialcornea.Iproposeatrainingplanthatwillallowmetoachievethisgoalfrom engineeringtechniquestobiologicalcharacterizationunderinvitro,exvivoandinvivomodels.
