Human Acellular Dermal Matrices Fabricated By Various Processes Elicit Diverse Host Responses in a Primate Model

Abstract

PURPOSE: An assortment of human acellular dermal matrices (HADMs), manufactured using a variety of decellularization and antiseptic protocols, are commercially available and used for various surgical applications. Although several studies in the literature have made direct comparison among multiple HADMs, few have linked in vivo biologic host response to tissue manufacturing method or resulting out-of-package biochemical and biomechanical attributes of the matrix. Here, we aim to evaluate 5 distinctly processed and disinfected HADMs in a nonhuman primate. MATERIALS AND METHODS: African Green monkeys were implanted either subcutaneously on the back with two, 1 × 1 cm pieces each of electron-beam irradiated HADM (AlloDerm/e-HADM) and gamma-irradiated HADM (DermACELL/g-HADM) for 1 month, or in the dynamically loaded site of the ventral abdominal wall with one, larger 3 × 7 cm piece of either electron-beam irradiated HADM (AlloDerm/e-HADM), freeze-dried gamma-irradiated HADM (AlloMax/g-HADM-FD), ethanol-stored aseptically processed HADM (Flex HD/EtOH-HADM), or freeze-dried aseptically processed HADM (DermaMatrix/HADM-FD) for either 1, 3, or 6 months. All HADM samples were harvested at the specified time points and evaluated histologically for cellular ingrowth, vascularity, and inflammatory response, whereas dynamically loaded HADM samples were additionally evaluated for regenerative response as judged by HADM–host interface integration and neo-collagen alignment. Host response established in these NHP models was compared with out-of-package in vitro mechanical properties as well as in vitro attributes established in previous studies. RESULTS: Out-of-package, e-HADM had significantly higher tensile strength (379.4 ± 26.2N) than g-HADM, EtOH-HADM, HADM-FD, and g-HADM-FD (233.2 ± 33.1N, 233.1 ± 126.2N, 211.6 ± 18.6N, and 104.0 ± 17.8N, respectively). In previous benchtop studies, e-HADM had also been found to have ultrastructural characteristics, acid-soluble collagen content, and degree of susceptibility to digestion by collagenase more similar to native tissues than g-HADM, EtOH-HADM, or g-HADM-FD.1 Subcutaneously implanted g-HADM samples demonstrated substantially greater inflammatory host response than e-HADM as determined through hematoxylin and eosin histologic analysis and immunohistochemically via anti–CD-68 antigen presence at 1-month implantation. In the dynamically loaded model, a greater inflammatory infiltrate was evident histologically and immunohistochemically (CD-68/CD-3/CD-20) for g-HADM-FD, EtOH-HADM, and HADM-FD, as compared with e-HADM. Subsequently, degree of HADMs to resist in vivo contraction and extent of incorporation was greater grossly for e-HADM than other HADMs and was supported by histologic fibroblast cell infiltration at the HADM–primate tissue interface. Likewise, collagen fibers could be observed to align linearly in the direction of dynamic forces for e-HADM, whereas other HADMs in the study tended to demonstrate a scar-like morphology histologically. Vascularization/integration was shown to increase in terms of vessel number and relative size for e-HADM and was generally not inflammation-associated, whereas g-HADM-FD, EtOH-HADM, and HADM-FD vessels were either less evident or associated with areas predominated by inflammatory cell infiltration. CONCLUSIONS: The data presented here appear to demonstrate a relationship between in vivo host response to HADMs in a nonhuman primate and benchtop attributes of these differently processed HADMs. Maintenance of structural, biochemical, and mechanical attributes of HADM products appears to be crucial for positive host response in terms of cellular infiltration and vascularization, leading to improved incorporation with low inflammatory characteristics. REFERENCE: 1. Sandor M, Leamy P, Assan P, et al. Relevant in vitro predictors of human acellular dermal matrix-associated inflammation and capsule formation in a nonhuman primate subcutaneous tissue expander model. Eplasty. 2017;17:e1.