Acellular Adipose Tissue Scaffold for Soft Tissue Reconstruction

Introduction

Soft tissue injury can arise from trauma, tumor resection or congenital defects. Current treatment options using autologous flaps or prosthetic implants have drawbacks that include donor site morbidity and capsular contracture, giving rise to the clinical need for a soft tissue replacement that can be used allogeneically and encourage host tissue regeneration in the defect. Adipose tissue can potentially provide a biologically instructive scaffold for soft tissue reconstruction. Using mechanical and chemical treatments to decellularize adipose tissue, the extracellular matrix can be retained for use as a biocompatible soft tissue filler.

Materials and Methods

Decellularization was carried out using mechanical or solvent-based extraction methods for lipid removal, followed by chemical treatments with 3% peracetic acid, 1% Triton-X100, and DNase. The degradation rate of the biomaterial can be further controlled by crosslinking the scaffold using hexamethylene diisocyanate or N-(3-dimethylaminopropyl)-N-ethylcarbodiimide. Cell viability was evaluated by seeding human adipose-derived stem cells (ASCs) on the matrix and all conditions proved conducive to cell growth.

To determine if adipose ECM holds an intrinsic ability to facilitate adipogenesis, ASCs were seeded on the adipose-derived scaffold and compared with human acellular dermis. Histology and gene expression were evaluated between 1-4 weeks for adipogenic differentiation. In vivo biocompatibility were assessed in both athymic mice (n=24) and Sprague Dawley rats (n=12) over 12 weeks. The rats were injected subcutaneously with 200 ul of acellular adipose ECM and athymic mice had ECM injections alone and in combination with ASCs. Volume measurements were taken every 2 weeks to monitor persistence and implants were fixed for histology at 1, 4, and 12 weeks.

Results and Discussion

Adipose tissue was successfully decellularized to produce an acellular matrix that provides both the structural support for reconstruction and instructional cues for host tissue repair processes. Adipose tissue formation was detected as early as one week after implantation with no signs of a severe immune response to the implanted matrix. The maintenance of a stable implant volume suggests that adipose-derived ECM can provide the structural and mechanical support necessary to repair defects while creating an instructive environment for soft tissue regeneration. 

Fig. 1 Decellularized adipose ECM after subcutaneous implantation in a Sprague-Dawley rat.

Fig. 2 Masson's trichrome staining showing de novo adipose tissue development in the implant after 2 weeks.