In vivo performance of decellularized tracheal grafts in the reconstruction of long length tracheal defects: Experimental study

Abstract

Background: The repair of long-segment tracheal lesions remains an important challenge. Nowdays no predictable and dependable substitute has been found. Decellularized tracheal scaffolds have shown to be a promising graft for tracheal transplantation, since it is non-immunogenic. Objective: Evaluate in vivo decellularized tracheal allografts performance to replace long tracheal segment. Methods: Forty-five swines underwent surgery as follows: Fifteen trachea donors and 30 receptors of decellularized trachea allografts. The receptors were randomly divided in five groups ( n = 6). In groups I and II, donor trachea segment was decellularized by 15 cycles with sodium deoxycholate and deoxyribonuclease, in group II, the allograft was reinforced with external surgical steel wire. Groups, III, IV, and V decellularization was reduced to seven cycles, supplemented with cryopreservation in group IV and with glutaraldehyde in group V. A 10 rings segment was excised from the receptor swine and the decellularized trachea graft was implanted to re-establish trachea continuity. Results: Both decellularization cycles caused decreased stiffness. All trachea receptors underwent euthanasia before the third post-implant week due to severe dyspnea and trachea graft stenosis, necrosis, edema, inflammation, hemorrhage, and granulation tissue formation in anastomotic sites. Histologically all showed total loss of epithelium, separation of collagen fibers, and alterations in staining. Conclusions: Both decellularization techniques severely damaged the structure of the trachea and the extracellular matrix of the cartilage, resulting in a no functional graft, in spite of the use of surgical wire, cryopreservation or glutaraldehyde treatment. An important drawback was the formation of fibrotic stenosis in both anastomosis.

Successful tracheal regeneration using biofabricated autologous analogues without artificial supports

“…Furthermore, excellent long-term clinical results have been reported in patients, including children, by culturing stem cells or tracheal consisting cells, or adding several growth factors in the decellularized trachea 20 . However, most studies have problems such as obstruction and degradation caused by granulation and deformation due to the reduced strength in the decellularization process 21 . Three requirements for application in tracheal substitutes, (1) mechanical strength, (2) biocompatibility, and (3) nutritional vascular network, remain to be met.…”

Cartilaginous Extracellular Matrix Enriched with Human Gingival Mesenchymal Stem Cells Derived “Matrix Bound Extracellular Vesicles” Enabled Functional Reconstruction of Tracheal Defect

“…[ 35 ] Although decellularized allogenous trachea, polymeric prosthesis or tissue engineered grafts presented advantages in recovering mechanical properties and structural integrity in tracheal reconstruction, insufficient re‐epithelialization, or slow mucosalization of tracheal substitutes is always life‐threatening owing to bacteria invasion, granulation related stenosis, excessive scarring, and mucus impaction. [ 36–38 ] Therefore, regenerating respiratory epithelium on grafts lumen must be completed as quickly as possible. Combining bioactive ACM and mechanically tough polymer is believed to be a promising strategy to reconstruct tracheal defects.…”

Preclinical and clinical orthotopic transplantation of decellularized/engineered tracheal scaffolds: A systematic literature review

“…Through chemical + physical strategies or chemical and enzymatic treatments + physical strategies it is possible to prepare structures with specific morphological characteristics, preserving the extracellular matrix composition and angiogenic factors, free from consistent donor cells and major histocompatibility complex (MHC) class I and II molecules (assuring for low immunogenicity); however, there is still no consensus in the optimal protocol to adopt, triggering the debate. 3 , 17 – 19 Controversies regard time required for scaffold preparation (time-consuming?) as well as recellularization by autologous mesenchymal stem cells differentiated into chondrocytes and/or airway cells (required?…”

“…The enzymes used included the DNase-I, 1 , 19 , 53 – 57 , 60 eventually mixed with the RNase 58 – 60 or trypsin. 18 …”