Decellularized dermis extracellular matrix alloderm mechanically strengthens biological engineered tunica adventitia-based blood vessels

Abstract

The ideal engineered vascular graft would utilize human-derived materials to minimize foreign body response and tissue rejection. Current biological engineered blood vessels (BEBVs) inherently lack the structure required for implantation. We hypothesized that an ECM material would provide the structure needed. Skin dermis ECM is commonly used in reconstructive surgeries, is commercially available and FDA-approved. We evaluated the commercially-available decellularized skin dermis ECM Alloderm for efficacy in providing structure to BEBVs. Alloderm was incorporated into our lab’s unique protocol for generating BEBVs, using fibroblasts to establish the adventitia. To assess structure, tissue mechanics were analyzed. Standard BEBVs without Alloderm exhibited a tensile strength of 67.9 ± 9.78 kPa, whereas Alloderm integrated BEBVs showed a significant increase in strength to 1500 ± 334 kPa. In comparison, native vessel strength is 1430 ± 604 kPa. Burst pressure reached 51.3 ± 2.19 mmHg. Total collagen and fiber maturity were significantly increased due to the presence of the Alloderm material. Vessels cultured for 4 weeks maintained mechanical and structural integrity. Low probability of thrombogenicity was confirmed with a negative platelet adhesion test. Vessels were able to be endothelialized. These results demonstrate the success of Alloderm to provide structure to BEBVs in an effective way.

Mimicking the Natural Basement Membrane for Advanced Tissue Engineering

“…Comercially available human decellularized dermal matrix (Glyaderm) was shown to enhance re-epithelialization and healed full thickness skin defects when seeded with adipose derived stem cells (ASC) in murine wound models . Similarly, AlloDerm, provided structure and support to biologically engineered blood vessels which were mechanically stronger than vessels lacking AlloDerm ECM . The group of da Mata Martins et al demonstrated the importance of choosing appropriate decellularizing techniques to preserve the ultrastructures of decellularized human cornea where the epithelial BM (EBM) was preserved.…”

“… 197 Similarly, AlloDerm, provided structure and support to biologically engineered blood vessels which were mechanically stronger than vessels lacking AlloDerm ECM. 183 The group of da Mata Martins et al demonstrated the importance of choosing appropriate decellularizing techniques to preserve the ultrastructures of decellularized human cornea where the epithelial BM (EBM) was preserved. This intact EBM structure was reported to differentiate the human embryonic stem cells to epithelial-like cells.…”

“…Collagen I provided mechanical support, and Matrigel offered key components of cell-adhesion present in BM, and when they were used in a perfusable microdevice, they offered support to intestinal stem cells for organoid formation. 182 The organs from which dECM have been harvested range from skin, 183 lung, 184 cornea, 185,186 bladder, 186 kidney, 187 placenta, 188,189 amniotic membrane, 190−192 cartilage, 193 adipose tissue, 194,195 esophagus, 195 and liver 196 and have been used in organ regeneration and in vitro model construction. Comercially available human decellularized dermal matrix (Glyaderm) was shown to enhance re-epithelialization and healed full thickness skin defects when seeded with adipose derived stem cells (ASC) in murine wound models.…”

Freeform 3D printing of vascularized tissues: Challenges and strategies

“…The main role of adventitia is to provide structural integrity to the whole vessel which includes collagen, ECMs, and fibroblasts. 28 , 29 On the other hand, media which is composed of smooth muscle cells (SMCs) and pericytes is the thickest layer among the three layers, and it renders load bearing capability. 30 Intima is an innermost layer of blood vessels which adjusts vascular tones and it is comprised of endothelial cells (ECs).…”

Perfusion decellularization and characterization of esophagus with preserved folded mucosa for clinical reconstruction

“…After decellularization, most of the cells, antigens, and other components would be removed. There are several successful cases for decellularized scaffolds including airway clinical transplantation [71] and more than 20 commercial products [72] (AlloDerm [73,74], AxoGen® [75], etc. )…”