Characterization of a biologically derived rabbit tracheal scaffold

Abstract

There is a clinical need to provide replacement tracheal tissue for the pediatric population affected by congenital defects, as current surgical solutions are not universally applicable. A potential solution is to use tissue engineered scaffold as the framework for regenerating autologous tissue. Rabbit trachea were used and different detergents (Triton x-100 and sodium deoxycholate) and enzymes (DNAse/RNAse) investigated to create a decellularization protocol. Each reagent was initially tested individually and the outcome used to design a combined protocol. At each stage the resultant scaffold was assessed histologically, molecularly for acellularity and matrix preservation. Immunogenicity of the final scaffold was assessed by implantation into a rat model for 4 weeks. Both enzymes and detergents were required to produce a completely acellular (DNA content 42.78 ng/mg) scaffold with preserved collagen and elastin however, GAG content were reduced (8.78 ± 1.35 vs. 5.5 ± 4.8). Following in vivo implantation the scaffold elicited minimal immune response and showed significant cellular infiltration and vasculogenesis. The luminal aspect of the implanted scaffold showed infiltration of host derived cells, which were positive for pan cytokeratin. It is possible to create biologically derived biocompatible scaffolds to address specific pediatric clinical problems. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2126-2135, 2017.

Limitations of recellularized biological scaffolds for human transplantation

“…The use of an acellular scaffold is based on the premise that any immune response should be minimal, thereby avoiding the need for immunosuppressant therapy. However, the evaluation process of most published studies only spans a few weeks to a few months (Fishman et al, ; Lange et al, ; Liu et al, ; Maughan et al, ; Mirmalek‐Sani et al, ; Wang, Johnson, et al, ). This raises the concern of monitoring a minimal immune response without considering a potential graft failure occurring later.…”

“…However, there are conflicting reports with regard to rejection of xenogeneic and allogeneic acellular scaffolds. Various studies report no or a weak immunogenic response (Cebotari et al, ; Coutu, Mahfouz, Loutochin, Galipeau, & Corcos, ; da Costa et al, ; Elliott et al, ; Fishman et al, ; Jeinsen et al, ; Lange, Shah, Birchall, Sibbons, & Ansari, ; Liu et al, ; Mirmalek‐Sani, Sullivan, Zimmerman, Shupe, & Petersen, ; Sayk, Bos, Schubert, Wedel, & Sievers, ; Wang, Wang, Zhang, Qiang, & Luo, ), whereas others show a significant immune response such as a fibrogenic response, chronic inflammatory reaction, stenosis, noninfectious swelling, edema and lymphatic infiltration, IgG deposition, and activation of complement system (Bastian et al, ; Cicha et al, ; Kasimir et al, ; Maughan et al, ; Rieder et al, ; Ruffer et al, ; Simon et al, ; Spark, Yeluri, Derham, Wong, & Leitch, ; Zheng et al, ). A similar discrepancy in immunogenic response has been noted for some FDA‐approved acellular scaffolds (Simon et al, ).…”

Selection of the optimum 3D‐printed pore and the surface modification techniques for tissue engineering tracheal scaffold in vivo reconstruction

“…Tracheal replacement therapy is undertaken to relieve the anastomotic tension . An ideal engineered tracheal matrix should support cell adhesion, proliferation, and have a similar mechanical force to the native tissue, which supports the structure of an open airway . At present, the methods based on the decellularized and the biosynthetic scaffolds are widely used .…”

“…3 An ideal engineered tracheal matrix should support cell adhesion, proliferation, and have a similar mechanical force to the native tissue, which supports the structure of an open airway. 4 At present, the methods based on the decellularized and the biosynthetic scaffolds are widely used. 2 The in vitro decellularized processing takes a long time, comes with a high risk of contamination and consumes more resources; donor shortages also limit its development.…”

“…6 Therefore, current research focuses on improving the stability of the overall extracellular matrix (ECM) architecture. 7 Recently, scholars have focused on absorbable biomaterials 4 ; polycaprolactone (PCL) has a slow rate of biodegradation in vivo, which can prevent problems caused by excessive degradation, such as postoperative tracheal softening, collapse and restenosis. 8 3D printing technology is based on the X, Y, and Z-based space and created with CT image or computer aided design (CAD).…”