Human Cadaveric Donor Cornea Derived Extra Cellular Matrix Microparticles for Minimally Invasive Healing/Regeneration of Corneal Wounds

Abstract

Biological materials derived from extracellular matrix (ECM) proteins have garnered interest as their composition is very similar to that of native tissue. Herein, we report the use of human cornea derived decellularized ECM (dECM) microparticles dispersed in human fibrin sealant as an accessible therapeutic alternative for corneal anterior stromal reconstruction. dECM microparticles had good particle size distribution (≤10 µm) and retained the majority of corneal ECM components found in native tissue. Fibrin–dECM hydrogels exhibited compressive modulus of 70.83 ± 9.17 kPa matching that of native tissue, maximum burst pressure of 34.3 ± 3.7 kPa, and demonstrated a short crosslinking time of ~17 min. The fibrin–dECM hydrogels were found to be biodegradable, cytocompatible, non-mutagenic, non-sensitive, non-irritant, and supported the growth and maintained the phenotype of encapsulated human corneal stem cells (hCSCs) in vitro. In a rabbit model of anterior lamellar keratectomy, fibrin–dECM bio-adhesives promoted corneal re-epithelialization within 14 days, induced stromal tissue repair, and displayed integration with corneal tissues in vivo. Overall, our results suggest that the incorporation of cornea tissue-derived ECM microparticles in fibrin hydrogels is non-toxic, safe, and shows tremendous promise as a minimally invasive therapeutic approach for the treatment of superficial corneal epithelial wounds and anterior stromal injuries.

Acellularized Uvea Hydrogel as Novel Injectable Platform for Cell‐Based Delivering Treatment of Retinal Degeneration and Optimizing Retinal Organoids Inducible System

“…In general, acellular ECM hydrogels have been widely applied in vivo, without obvious adverse responses after being injected into tissues such as the heart, [59] liver, [60] brain, [61] spinal cord, [31] and cornea. [33,34,62,63] However, there have been no previous reports investigating the application of decellularized ECM hydrogels for repairing damaged retinas and restoring vision. However, some groups have fabricated other ECM hydrogels (such as hyaluronan, methylcellulose, alginate, collagen, and musselinspired polydopamine) for therapeutic purposes.…”

Transcriptomic Profiling of Human Limbus-Derived Stromal/Mesenchymal Stem Cells—Novel Mechanistic Insights into the Pathways Involved in Corneal Wound Healing

“…These cells are capable of differentiating into the native keratocyte phenotype [ 22 , 23 ]. Recent studies by Orozco Morales et al [ 70 ], Hertsenberg et al [ 76 ], Weng et al [ 77 ] Chameettachal et al [ 78 ] and Chandru et al [ 79 ] have shown the potential of these cells in healing the cornea both in vitro and in vivo in animal models. However, the underlying mechanisms of how these cells achieve the scarless wound healing is not clearly studied.…”

In vivo biocompatibility evaluation of in situ-forming polyethylene glycol-collagen hydrogels in corneal defects

“…For instance, the PEG-based materials ReSure (Ocular Therapeutix Inc., MA, USA) or OcuSeal (Beaver-Visitec International, MA, USA) cannot be used as filling biomaterials due to fast and uncontrollable polymerization, low adhesiveness, and lack of the mechanical properties required for regeneration 20 , 21 . Preclinical pilot study was demonstrated using human cadaveric donor cornea from ECM microparticles have been used; however, immunologic reactions may be problematic 22 . The newly introduced GelCORE, a gelatin-based adhesive, also showed in vivo biocompatibility and high tissue adhesion for 14 days 7 .…”

“…Corneal mechanical strength and structural integrity originate mainly from the collagen present in the stroma 22 , 28 . The mechanical properties of non-crosslinked collagen are difficult to control, which can pose a challenge.…”