In-body tissue-engineered collagenous connective tissue membranes (BIOSHEETs) for potential corneal stromal substitution

Abstract

There is a severe shortage of donor cornea for transplantation in many countries. Collagenous connective tissue membranes, named BIOSHEETs, grown in vivo were successfully implanted in rabbit corneal stroma for in vivo evaluation of their suitability as a corneal stromal substitute to solve this global donor shortage. BIOSHEETs were prepared by embedding silicone moulds into dorsal subcutaneous pouches in rabbits for 1 month and stored in glycerol. After re-swelling in saline and trephining, disk-shaped BIOSHEETs (4 mm diameter) were allogeneically implanted into stromal pockets prepared in the right cornea of seven rabbits. Clinical tests for corneal thickness and transparency, and tissue analyses were performed. Because the BIOSHEETs (thickness, 131 ± 14 µm) obtained were opaque immediately after implantation, the transparency of the cornea decreased. The total thickness of the BIOSHEET-implanted cornea increased from 364 ± 21.0 µm to 726 ± 131 µm. After 4 weeks' implantation, the thickness of the cornea stabilized (493 ± 80 µm at 4 weeks and 447 ± 46 µm at 8 weeks). The transparency of the cornea increased progressively with time of implantation. The random orientation of collagen fibrils in the original BIOSHEETs tended to be homogeneous, similar to that of the native stroma. No inflammatory cells accumulated and fibroblast-like cells infiltrated the implant. The BIOSHEETs showed high biocompatibility with stromal tissues; however, further studies are needed to test its functional aspects. Although this research is only intended as a proof of concept, BIOSHEETs may be considered a feasible corneal stromal replacement, especially for treating visual impairment caused by stromal haze. Copyright © 2013 John Wiley & Sons, Ltd.

Urinary bladder reconstruction using autologous collagenous connective tissue membrane “Biosheet” induced by in-body tissue architecture

“…We have previously found that Biosheets produced by iBTA technology can recruit tissue stem cells from native tissue, and that these stem cells then mature and undergo proliferation (17). Biosheets were reconstructed in a manner analogous to native tissue, such as cornea, trachea, diaphragm, and esophagus (17,(23)(24)(25).…”

Three-Month Outcomes of Aortic Valve Reconstruction Using Collagenous Membranes (Biosheets) Produced by in Body Tissue Architecture in A Goat Model: A Preliminary Study

“…This technology has been successfully applied to the engineering of cardiovascular tissues, of vascular grafts as biotubes, or of heart valve-like tissues as biovalves. Biosheets, which are iBTA-induced membranous tissues, have been applied to the cornea [3], as well as to the repair of the diaphragm [4], esophagus [5], and trachea [6]. The studies that have reported on this technology indicated the possibility of tissue regeneration, self-repair, and growth adaptability.…”

One year Rat Study of iBTA-induced “Microbiotube” Microvascular Grafts With an Ultra-Small Diameter of 0.6 mm

“…This technology has ushered in a new phase of regenerative medicine. 3 Grafts formed by iBTA can be made in any shape and form by suitably designed distributions of moulds; consequently, tubular connective tissue (biotube), 3 membranous tissue (biosheet), 4 and three dimensional valve shaped tissue (biovalve) 5 have been fabricated and transplanted in several animal models with satisfactory function.…”