Tissue Engineering Meets Nanotechnology: Molecular Mechanism Modulations in Cornea Regeneration

Abstract

Nowadays, tissue engineering is one of the most promising approaches for the regeneration of various tissues and organs, including the cornea. However, the inability of biomaterial scaffolds to successfully integrate into the environment of surrounding tissues is one of the main challenges that sufficiently limits the restoration of damaged corneal tissues. Thus, the modulation of molecular and cellular mechanisms is important and necessary for successful graft integration and long-term survival. The dynamics of molecular interactions affecting the site of injury will determine the corneal transplantation efficacy and the post-surgery clinical outcome. The interactions between biomaterial surfaces, cells and their microenvironment can regulate cell behavior and alter their physiology and signaling pathways. Nanotechnology is an advantageous tool for the current understanding, coordination, and directed regulation of molecular cell–transplant interactions on behalf of the healing of corneal wounds. Therefore, the use of various nanotechnological strategies will provide new solutions to the problem of corneal allograft rejection, by modulating and regulating host–graft interaction dynamics towards proper integration and long-term functionality of the transplant.

Human SMILE-Derived Stromal Lenticule Scaffold for Regenerative Therapy: Review and Perspectives

“…Combining an ECM scaffold with nanoparticles (NPs) can promote targeted and controlled drug release and improve the bioavailability and biodistribution of therapeutic molecules [ 128 , 129 , 130 ]. An in vivo study on Parkinson’s disease drug delivery showed that the intracranial implantation of scaffolds embedded with dopamine-loaded cellulose acetate phthalate nanoparticles resulted in sustained drug delivery.…”

“…Some limitations of tissue-engineered corneal transplants are suboptimal integration and the risk of tissue rejection, especially in the case of treating acutely damaged and highly inflamed tissues [ 37 , 182 ]. Poor interactions between the graft and host tissue could influence multiple molecular events, including healing, inflammation, ECM remodeling, and cell death at the graft host site [ 16 , 129 , 183 ]. Corneal scaffold fabrication with nanomaterials has the potential to improve the physicochemical properties that enhance graft integration in the host tissue [ 129 ].…”

“…Poor interactions between the graft and host tissue could influence multiple molecular events, including healing, inflammation, ECM remodeling, and cell death at the graft host site [ 16 , 129 , 183 ]. Corneal scaffold fabrication with nanomaterials has the potential to improve the physicochemical properties that enhance graft integration in the host tissue [ 129 ]. They can also be fabricated with NPs, such as silver or gold NPs, to modulate wound healing and for cell repopulation.…”

“…In addition, NPs can be used to manage post-implantation complications, such as inflammation, secondary infections, and neovascularization in the host area. Various nanocarrier-based therapeutic agents can be used in the scaffold fabrication phase [ 129 , 184 ]. With such scenarios as these, the use of lenticule scaffolds incorporated with gold NPs for stromal implantation could enhance stromal cell viability, manage inflammation by regulating lymphocytic and platelet activation after injury, and potentially have an impact on nerve growth and repair in tissue regeneration.…”

Editorial for the Special Issue on Emerging and Disruptive Next-Generation Technologies for POC: Sensors, Chemistry and Microfluidics for Diagnostics

“…The molecular and cellular modulation indeed is important and necessary for successful graft integration, post-surgery clinical outcome and long-term survival. The authors specifically addressed corneal tissue engineering, which has attracted great interest recently, due to the attempts to avoid many of the complications encountered in traditional donor corneal transplantation [5]. The involvement of cells could not only allow the creation of a cornea analog, which should provide high optical transparency, mechanical integrity and proper cell behavior, leading to effective re-epithelialization, but also give promises for the full regeneration and integration of the graft.…”