Long-Term Implantation of Preadipocyte-Seeded PLGA Scaffolds

Abstract

Studies were performed in a long-term effort to develop clinically translatable, tissue engineered adipose constructs for reconstructive, correctional, and cosmetic indications. Rat preadipocytes were harvested, isolated, expanded ex vivo, and seeded within PLGA scaffolds. Preadipocyte-seeded and acellular (control) scaffolds were implanted for 1-12 months. Explanted scaffolds were stained with osmium tetroxide, processed, and counterstained using H&E. Quantitative histomorphometric analysis was performed on all tissue sections to determine the amount of adipose tissue formed. Analyses revealed maximum adipose formation at 2 months, followed by a decrease at 3 months, and complete absence of adipose and PLGA at 5-12 months. These results extend a previous short-term study (Tissue Engineering 1999;5:134) and demonstrate that adipose tissue can be formed in vivo using tissue engineering strategies. However, the long-term maintenance of adipose tissue remains elusive.

Human clinical experience with adipose precursor cells seeded on hyaluronic acid-based spongy scaffolds

“…The three-dimensional geometry of the native ECM constrains cells during regeneration and provides space for tissue development [25] and in vitro studies have shown that the scaffold geometry promotes preadipocyte differentiation [31]. The architecture of adipose tissue has been reconstructed using adipose-derived stromal cells seeded onto different scaffold materials [6][7][8]13,14]. Hyaluronic acid-based scaffolds have been used clinically to successfully direct chondrocyte development [32][33][34].…”

“…Materials that meet fundamental requirements such as controlled degradation, cytotoxicity and immunogenity are needed. Research reports have shown successful and reproducible inoculation and culturing of adipocyteand preadipocyte-precursor cells (preadipocytes and progenitors, respectively) on synthetic [6,7] or natural [8] prefabricated scaffolds [9] with subsequent differentiation in vitro or adipose tissue formation in vivo [10]. The scaffolds within these bio-hybrids provided the seeded cells specific attachment or binding sites, shaped the tissue construct and functioned as geometrical environments in which not only cells received their essential cues for a structural cell organization and cellular behaviour but also cellular function was modulated [11,12].…”

Strategies for Bioengineered Scaffolds that Support Adipose Stem Cells in Regenerative Therapies

“…Patrick et al demonstrated that ASCs seeded into a PLGA scaffold and implanted subcutaneously into rats showed maximum adipose tissue formation after 2 months, but noted that between 3 and 12 months, a complete loss of reconstructed adipose tissue and degeneration of the PLGA scaffold occurred [77]. This loss of tissue may arise from the degradation of the scaffolding, especially since signs of PLGA degradation were apparent as early as 1 month post-transplantation.…”

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

“…Structural biopolymer carriers such as sponges or nonwoven meshes provide a permissive microenvironment in which seeded preadipocytes proliferate and differentiate. In the absence of seeded cells, common scaffold materials alone have not been demonstrated as having appreciable adipogenic activity [13,14].…”

“…Polylactide glycolic acid (PLGA), polyglycolic acid (PGA), hyaluronan, and collagen-I in the form of nonwoven meshes or sponges have been evaluated as three-dimensional carriers for ex vivo expanded preadipocytes with varying success [13][14][15][16]. The in vivo efficacy of constructs in generating mature adipose tissue has been clearly correlated to the in vitro cell inoculation of the scaffolds and on the structure and type of biopolymer used [17].…”