47. Flowable Decellularized Dermal Hydrogel Improves Integration of Acellular Dermal Matrices

Abstract

PURPOSE: Acellular dermal matrices (ADM) have revolutionized pre-pectoral implant-based breast reconstruction allowing for improved pocket control and more rapid expansion but with the drawback of an increased risk of seroma that can lead to major complications including implant loss. The majority of these complications are a result of delayed or insufficient wound healing and integration of the ADM. ADM bio-integration can be accelerated by increasing the surface area of the ADM:host soft tissue interface. To address the issue of persistent contact of the ADM with the patient, we investigated the application of a hydrogel, derived from ADM to increase the conduction of the cells and molecular signals and increase vascularization, is critical to biointegration. METHODS: C57bl/6 mice received bilateral subcutaneous pockets. A 5mm diameter ADM implant was placed into each pocket and into one, 0.5 mL of decellularized dermal hydrogel was injected. Implants were harvested at terminal endpoints at 1, 3, and 6 weeks. Flow cytometry was performed to assess a panel of 12 macrophage markers (pan-, M1, M2, or transition) to evaluate inflammatory effects. Immunohistochemical staining for vimentin was used to assess fibroblast migration into the ADM. Hematoxylin and eosin (H&E) staining of implant cross sections was performed for pathological analysis of fibrosis via capsule formation. Capsule thickness, cellularity, foreign bodies, and smooth muscle actin (SMA) were graded (0 = none, 1 = mild, 2 = moderate, 3 = severe). RESULTS: H&E staining demonstrated that the dermal hydrogel persisted adjacent to the ADM implant. Flow cytometry results demonstrated that DPD hydrogel and ADM did not elicit an increased macrophage response compared to ADM implants alone. Vimentin expression demonstrated an upward trend in fibroblast infiltration from 3 to 6, with the dermal hydrogel group fibroblast increase outpacing that of the ADM control. Pathological analysis showed minimal capsule formation and no significant increase in fibrosis between hydrogel and no hydrogel groups. CONCLUSIONS: Our dermal hydrogel was able to flow easily into the surgical pocket, polymerized at physiological temperatures, and remained in place over the course of 6 weeks, demonstrating its potential to bridge the gap between ADM and the overlying skin envelope within human breast reconstructions. Our murine model revealed that the dermal hydrogel did not lead to an increased inflammatory immune response, with no statistical difference in fibrosis scores between t ADM-only implants. Although not statistically significant, immunohistochemistry quantifying the amount of vimentin present in the hydrogel-ADM complex showed promising trends with ADM integration into host tissue. Future work will include expansion of the model to incorporate radiation in order to examine the ability of the dermal hydrogel to aid in wound healing and ADM integration within an environment mirroring that seen in irradiated mastectomy cases.