Characterization of Inflammatory and Fibrotic Aspects of Tissue Remodeling of Acellular Dermal Matrix in a Nonhuman Primate Model

Abstract

Background: Human acellular dermal matrices (hADMs) are applied in various soft tissue reconstructive surgeries as scaffolds to support tissue remodeling and regeneration. To evaluate the clinical efficacy of hADM implants, it is integral that the hADM does not induce a host chronic inflammatory response leading to fibrotic encapsulation of the implant. In this study, we characterized the inflammatory and fibrosis-related tissue remodeling response of 2 commercial hADM products (SimpliDerm and AlloDerm RTU) in a nonhuman primate model using histology and gene expression profiling. Methods: Eighteen African green monkeys with abdominal wall defects were applied to evaluate the performance of SimpliDerm and AlloDerm RTU implants (N = 3) at 2, 4, and 12-weeks post-implantation. Using histology and gene expression profiling, tissue responses such as implant integration, degradation, cell infiltration, immune response, neovascularization, and pro-fibrotic responses over time were evaluated. Results: SimpliDerm showed a lower initial inflammatory response and slower implant degradation rate than AlloDerm RTU evidenced by histomorphological analysis. These factors led to a more anti-inflammatory and pro-remodeling microenvironment within SimpliDerm, demonstrated by lower TNFα levels and lower expression levels of pro-fibrotic markers, and promoted tissue repair and regeneration by 3-months post-implantation. Conclusions: Overall, histology and gene expression profiling analyses shown in this study demonstrated an effective model for analyzing hADM performance in terms of host inflammatory and fibrotic response. Further studies are warranted to fully evaluate the utility of this novel hADM in the clinical setting and verify the prognosis of our pre-clinical analysis model.

Clinical Outcomes of Acellular Dermal Matrix (SimpliDerm and AlloDerm Ready-to-Use) in Immediate Breast Reconstruction

“…Per AlloDerm’s Instructions For Use (IFU), electron beam irradiation is used to sterilize AlloDerm RTU to a Sterility Assurance Level (SAL) of 10 -3 whereas SimpliDerm’s IFU states that it is terminally sterilized to a SAL of 10 -6 using a proprietary ionizing radiation system. While these processing methods may not affect extracellular matrix stability, the divergent sterility levels could affect microbial colonization vulnerability [ 15 ]. Other potential benefits of the proprietary processing methods of SimpliDerm have been elucidated in rigorous preclinical studies.…”

“…Other potential benefits of the proprietary processing methods of SimpliDerm have been elucidated in rigorous preclinical studies. For example, a non-human primate model demonstrated that SimpliDerm facilitates host responses that foster remodeling of the hADM into native tissue [ 15 ]. In that study, SimpliDerm demonstrated a milder initial inflammation, more gradual implant degradation, reduced expression of profibrotic genes, and reduced long-term inflammatory markers compared to the host response to AlloDerm RTU.…”

“…Preclinical study results in a comparative, clinically relevant non-human primate model suggest that SimpliDerm may be biologically superior to an established hADM (AlloDerm® ready-to-use (RTU), Allergan Medical, Irvine, USA) in the host response to the implant. This comparison study found that SimpliDerm degraded more gradually, caused a lesser initial inflammatory reaction, and expressed less pro-fibrotic markers and proinflammatory cytokines compared to AlloDerm RTU [ 15 ]. The observed differences in the pre-clinical host response to these hADMs suggest that the use of SimpliDerm leads to a reduced inflammatory and fibrotic response, and improved remodeling compared to AlloDerm RTU.…”

Comparison of 30-day Clinical Outcomes with SimpliDerm and AlloDerm RTU in Immediate Breast Reconstruction

“…As demonstrated in a recent preclinical study, the intact ECM of SimpliDerm enhances and supports neovascularization, cell migration, tissue incorporation, and a modulated immune response that fosters remodeling of the hADM into native tissue. 15 …”

Application of Allogeneic Human Acellular Dermal Matrix Reduces the Incidence of Fistula in Hypospadias Repair

“…HADM is both cell-free and major histocompatibility complex (MHC) -free; it does not trigger immune rejection, and it has good histocompatibility. To ensure the safety and efficacy of HADM in clinical applications, investigators have evaluated its possible host-graft rejection and fibrotic reactions in animal experiments ( 5 , 6 ). To date, HADM has been successfully used in the repair of urethral stricture, with positive clinical effects ( 7 ).…”