Advanced scaffold for adipose tissue reconstruction

Abstract

Adipose tissue is a large loose connective tissue with functions comprising thermogenesis, homeostasis, metabolic activity and cushioning of bordering tissue layers. The tissue is predominantly composed of adipocytes and importantly contributes to the individual body shape. Loss of the fatty tissue due to trauma or disease often results in disfigurement, which affects patients physically as well as emotionally. Different surgical and scientific approaches have been studied to address this problem; in this regard tissue engineered scaffolds have received increased attention. Although there has been significant development in the efforts to address tissue loss, the reconstruction and maintaining of tissue with large dimensions remains a challenge. Hence, the overall aim of this project was to engineer a bulk scaffold suitable for adipose tissue reconstruction. The scaffold, cell source and extracellular signalling aspects of a tissue engineering strategy were approached to design a scaffold suitable for restoring adipose tissue defects of large dimensions. A particulate leaching method was developed and combined with the application of different freezing temperatures to produce a range of microporous macroporous gelatin scaffolds. Constructs were physically characterised for suitability in cell based studies. Scaffold design was investigated through biological characterisation using adipose derived stem cells (ADSCs) and an artificial ADSC stem cell niche was created through the utilisation of extracellular matrix components. The artificial environment was combined with the scaffolds and evaluated to support adipogenesis. A range of novel microporous macroporous scaffolds were produced, differing in micropore size range. Selection of scaffolds with defined features resulted in two constructs with a physical and biological profile suitable for adipose tissue construction. The scaffolds displayed high porosity and the materials supported ADSC viability and proliferation. Furthermore, cells were easily absorbed throughout the whole construct. The final resulting composite scaffold consisting of scaffold and artificial ADSC stem cell niche displayed in vitro support of adipogenesis. Concluding, a platform of novel composite adipogenic regeneration scaffolds were constructed that support adipogenesis as well as the preservation of ADSC stemness. Further, the gelatin sponges display a physical and biological profile suitable for adipose tissue reconstruction.