Engineered Soft Tissue Substitutes

While the implications of selectively manipulating fat tissue growth certainly include the treatment of obesity, there is a tremendous clinical utility for making fat grow. An ideal soft tissue substitute for reconstructive and aesthetic surgery has still not been identified. Alloplastic implants are prone to complications such as extrusion, infection, and capsular contracture. Autologous fat transplantation will undergo resorption. Tissue flap reconstruction is effective in many cases, but still has inherent donor site morbidity. A durable tissue engineered implant using a patient's own cells may represent a better clinical option.

Preadipocytes, the mesenchymal precursors to fat cells, are abundant within adipose tissue and can be harvested with low risk by minimally invasive procedures. These cells can be expanded in culture and induced to differentiate into mature adipocytes. The purpose of this study is to engineer a soft tissue implant using human preadipocytes seeded on a flexible three-dimensional framework and implanted in a nude mouse model. Basement membrane proteins coated on the framework and suspended in hydrogels that fill the scaffold will be employed to promote adherence and proliferation of preadipocytes.

We hypothesize that a mesh biomaterial folded in layers to form a three-dimensional scaffold and infiltrated with a biodegradable hydrogel containing basement membrane proteins will promote the proliferation and differentiation of human preadipocytes when implanted in a nude mouse. This combination of a flexible framework and supportive microenvironment may create a viable and durable adipocyte implant.

As such, the goals of this project are to:

1. Evaluate the adherence of human preadipocytes to several potentially useful biomaterial scaffolds, including poly(propylene) mesh and porcine small intestine submucosa (SIS).
2. Investigate the capacity of preadipocytes to replicate and differentiate in vitro when seeded on these scaffolds.
3. Elucidate the ability of human preadipocytes to replicate and differentiate in vitro when co-cultured with a biodegradable hydrogel containing basement membrane proteins.
4. Determine the ability of human preadipocytes to generate mature adipose tissue when seeded on biomaterial scaffolds and implanted in a nude mouse.

Key Investigators: J. Peter Rubin, M.D., Kacey G. Marra, Ph.D.