Autologous In Vivo Adipose Tissue Engineering in Hyaluronan-Based Gels—A Pilot Study

Abstract

Background. There is a major clinical need for strategies for adequately reconstructing the soft tissue defects found after deep burns, tumor resection, or trauma. A promising solution is adipose tissue engineering with preadipocytes, stem-cell derived precursors of the adipose tissue, implanted within biomaterials. This pilot study evaluated hyaluronan gels mixed with autologous undifferentiated preadipocytes in a pig model for their potency to generate new fat.Materials and methods. Preadipocytes were isolated from intra-abdominal pig fat by collagenase digestion, plated on fibronectin-coated culture dishes in Dulbecco's Modified Eagle Medium/Ham's F12 (Biochrom, Berlin, Germany) combined with 10% pig serum, expanded, and mixed with hyaluronan gel. Two types of gels with varying degrees of amidation of the carboxyl groups were tested (HYADD3, HYADD4). Cell-loaded gels and unseeded controls were injected subcutaneously into the ears of three pigs, explanted at 6 wk, and analyzed histologically.Results. Both cell-loaded specimens were detected macroscopically. They demonstrated a slight volume effect with limited stability after 6 wk. Unloaded HYADD3 and HYADD4 controls could not be identified at the time of explantation. Histology of HYADD3 revealed islets of mature adipocytes and vessels embedded in fat tissue surrounded by gel. In contrast, no fat formation was found in HYADD4 gels when implanted in the ear.Conclusions. Histological findings demonstrate that HYADD3 is a promising gel for generating adipose tissue. Even though HYADD3 might be a potential material for the reconstruction of small tissue defects, the question remains as to whether the adipose tissue within the gel is attributable to preadipocyte maturation or ingrowth from neighboring tissue.

Adipose Tissue Engineering in Three-Dimensional Levitation Tissue Culture System Based on Magnetic Nanoparticles

“…44 Notable progress in 3D tissue engineering has been recently achieved in mimicking the in vivo WAT microenvironment. 20,[45][46][47][48] However, so far reported studies have been based on scaffolds and custom-made bioreactors that do not allow for easy translation. 12,49,50 Three-dimensional aqueous-derived silk scaffolds have been previously used to coculture endothelial cells and human ASC that could be induced to undergo adipogenesis.…”

Injectable hydrogels

“…144,145 In contrast, preformed, noninjectable systems have shown limited therapeutic efficacy due to the often inadequate capacity to conform to host defect size and shape and the inability to seed cells deep into the scaffold. 146,147 One important drawback for some injectable polymeric scaffolds is that they can be mechanically weak, limiting their potential in load-bearing applications, such as orthopedic TE. 147 However, several means of addressing this issue have been explored-for example, hydrogels reinforced with rigid microspheres, as discussed in more detail in later sections.…”

Three-dimensional culture models of mammary gland

“…31 The development of a fat-pad, a volume of adipose in which epithelial sheets can form tubular structures has already been much advanced through adipose tissue engineering. [62][63][64] To date the thrust of research has centered around the challenges of providing a suitable scaffold that supports proliferation and differentiation, minimizing the loss in mass or volume with culture time, a noted affect of in vivo implantation and adequate 3D seeding and stimulation with exogenous adipogenic factors. While collagen has numerous advantages as a biomaterial, it demonstrates significant mass loss when implanted in vivo.…”