Development of volume-stable adipose tissue constructs using polycaprolactone-based polyurethane scaffolds and fibrin hydrogels

Abstract

Adipose tissue engineering aims at the restoration of soft tissue defects and the correction of contour deformities. It is therefore crucial to provide functional adipose tissue implants with appropriate volume stability. Here, we investigate two different fibrin formulations, alone or in combination with biodegradable polyurethane (PU) scaffolds as additional support structures, with regard to their suitability to generate volume-stable adipose tissue constructs. Human adipose-derived stem cells (ASCs) were incorporated in a commercially available fibrin sealant as well as a stable fibrin hydrogel previously developed by our group. The composite constructs made from the commercially available fibrin and porous poly(ε-caprolactone)-based polyurethane scaffolds exhibited increased volume stability as compared to fibrin gels alone; however, only constructs using the stable fibrin gels completely maintained their size and weight for 21 days. Adipogenesis of ASCs was not impaired by the additional PU scaffold. After induction with a common hormonal cocktail, for constructs with either fibrin formulation, strong adipogenic differentiation of ASCs was observed after 21 days in vitro. Furthermore, upregulation of adipogenic marker genes was demonstrated at mRNA (PPARγ, C/EBPα, GLUT4 and aP2; qRT-PCR) and protein (leptin; ELISA) levels. Stable fibrin/PU constructs were further evaluated in a pilot in vivo study, resulting in areas of well-vascularized adipose tissue within the implants after only 5 weeks. Copyright © 2013 John Wiley & Sons, Ltd.

Delivered adipose‐derived stromal cells improve host‐derived adipose tissue formation in composite constructs in vivo

“…Adipose tissue development within these constructs was proven in a pilot study over 5 weeks in a nude mouse model. Utilizing an integrated arteriovenous bundle, distinct vascularization within the constructs in vivo was shown . However, the necessity and the impact of the implanted cells on tissue development in these constructs were not assessed.…”

“…In this study we used biodegradable polyurethane scaffolds in combination with a long‐term stable fibrin gel as cell carriers, which were seeded with ASCs, to develop volume‐stable, transplantable adipose tissue constructs. In a previous study, a comprehensive in vitro characterization displayed the viability and adipogenic properties of the cells in the cultured constructs . The aim of the present study was to evaluate the impact of the transplanted ASCs on tissue development in vivo by comparing ASC‐seeded versus unseeded constructs in a nude mouse model with a vascular pedicle in the constructs upon implantation.…”

In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid‐derived stem cells

“…[25] Fibrin is a versatile biopolymer that has a critical role in blood clotting, cellular-matrix interactions, wound healing, and angiogenesis, [29][30][31] and is widely used as a biomaterial for engineered adipose, dermal, and cardiovascular tissues. [32][33][34] Like most other natural materials though, the main disadvantages of using fibrin as a scaffold are low mechanical stiffness and rapid degradation, [35,36] both of which can be mitigated by incorporation of PEG, an FDA-approved polymer with a wide range of medical and industrial applications. [25,37,38] Based on this data, we hypothesized that subcutaneously injecting AFSC-seeded fibrin/PEG hydrogels in immunodeficient mice would both induce a fibrin-driven angiogenic response and promote AFSC-derived neovascularization.…”

Temporal and spatial patterning of transgene expression by near-infrared irradiation

“…In experiments which followed the progress of implanted hydrogels for nearly a month, we observed that shrinkage of composites occurred at a same rate as matrices free of the metal component, dispelling concerns relating to a potential inhibition of the natural fibrinolysis process that could limit scaffold remodeling into tissue. For those tissue engineering applications where optimal shape integrity and stability of the scaffold are required for defined periods of time, HGNPs may be incorporated in hydrogel formulations designed to prolong the life of fibrin matrices, containing, for example, proteolytic or fibrinolytic inhibitors [23-26], cross-linking enzymes such as the transglutaminasa factor XIIIa [27] or reinforcing synthetic polymers such as polyethylene glycol [28] or polyurethane [29]. A remaining issue concerns the toxicity of HGNPs.…”