RESUMO
BACKGROUND: Complex abdominal wall reconstruction using biologic mesh can lead to increased recurrence rates, nonincorporation, and high perioperative costs. We developed a novel decellularization method and applied it to porcine muscle fascia to mirror target-tissue architecture. The aims of this study were to analyze mechanical strength and tissue-graft incorporation. METHODS: After serial decellularization, muscle-fascia mesh was created and tested for mechanical strength and DNA content. The muscle-fascia mesh was implanted subcutaneously in rats (n = 4/group) and the cohorts killed 1 to 4 weeks later. Explants were examined histologically or immunohistochemically. RESULTS: Mechanical testing demonstrated equivalent strength compared with a commercially available biological mesh (AlloDerm), with mechanical strength attributable to the fascia component. Grafts were successfully implanted with no observable adverse events. Gross necroscopy revealed excellent subdermal scaffold engraftment. Microscopic evaluation identified progressive collagen deposition within the graft, neoangiogenesis, and presence of CD34 positive cells, in the absence of discernable graft rejection. CONCLUSION: This study confirms a decellularization process can successfully create a DNA-free composite abdominal wall (muscle-fascia) scaffold that can be implanted intraspecies without rejection. Expanding this approach may allow exploitation of the angiogenic capacities of decellularized muscle, concomitant with the inherent strength of decellularized fascia, to perform preclinical analyses of graft strength in animal models in vivo.
Assuntos
Músculos Abdominais/cirurgia , Parede Abdominal/cirurgia , Materiais Biocompatíveis , Fáscia , Próteses e Implantes , Alicerces Teciduais , Animais , Biópsia , Imuno-Histoquímica , Masculino , Teste de Materiais , Fenômenos Mecânicos , Modelos Animais , Ratos , Telas Cirúrgicas , SuínosRESUMO
There are more than 3 million breast cancer survivors living in the United States of which a significant number have undergone mastectomy followed by breast and nipple-areolar complex (NAC) reconstruction. Current strategies for NAC reconstruction are dependent on nonliving or nonpermanent techniques, including tattooing, nipple prosthetics, or surgical nipple-like structures. Described herein is a tissue engineering approach demonstrating the feasibility of an allogeneic acellular graft for nipple reconstruction. Nonhuman primate (NHP)-derived NAC tissues were decellularized and their extracellular matrix components analyzed by both proteomic and histological analyses. Decellularized NHP nipple tissue showed the removal of intact cells and greatly diminished profiles for intracellular proteins, as compared with intact NHP nipple tissue. We further evaluated the biocompatibility of decellularized grafts and their potential to support host-mediated neovascularization against commercially available acellular dermal grafts by performing in vivo studies in a murine model. A follow-up NHP pilot study evaluated the host-mediated neovascularization and re-epithelialization of onlay engrafted decellularized NAC grafts. The murine model revealed greater neovascularization in the decellularized NAC than in the commercially available control grafts, with no observed biocompatibility issues. The in vivo NHP model confirmed that the decellularized NAC grafts encourage neovascularization as well as re-epithelialization. These results support the concept that a biologically derived acellular nipple graft is a feasible approach for nipple reconstruction, supporting neovascularization in the absence of adverse systemic responses. Impact statement Currently, women in the United States most often undergo a mastectomy, followed by reconstruction, after being diagnosed with breast cancer. These breast cancer survivors are often left with nipple-areolar complex (NAC) reconstructions that are subsatisfactory, nonliving, and/or nonpermanent. Utilizing an acellular biologically derived whole NAC graft would allow these patients a living and permanent tissue engineering solution to nipple reconstruction.