Abstract
The use of cell-free scaffolds for the regeneration of clinically relevant volumes of soft tissue has been challenged, particularly in the case of synthetic biomaterials, by the difficulty of reconciling the manufacturing and biological performance requirements. Here, we investigated in vivo the importance of biomechanical and biochemical cues for conditioning the 3D regenerative microenvironment towards soft tissue formation. In particular, we evaluated the adipogenesis changes related to 3D mechanical properties by creating a gradient of 3D microenvironments with different stiffnesses using 3D Poly(Urethane-Ester-ether) PUEt scaffolds. Our results showed a significant increase in adipose tissue proportions while decreasing the stiffness of the 3D mechanical microenvironment. This mechanical conditioning effect was also compared with biochemical manipulation by loading extracellular matrices (ECMs) with a PPAR-γ activating molecule. Notably, results showed mechanical and biochemical conditioning equivalency in promoting adipose tissue formation in the conditions tested, suggesting that adequate mechanical signaling could be sufficient to boost adipogenesis by influencing tissue remodeling. Overall, this work could open a new avenue in the design of synthetic 3D scaffolds for microenvironment conditioning towards the regeneration of large volumes of soft and adipose tissue, with practical and direct implications in reconstructive and cosmetic surgery.
Highlights
Process is one of the most challenging among connective tissues due to its structural and mechanical complexity and sensitivity to signals, such as the ones from hormone and nervous s ystems[10,11]
3 star-like polyester triols obtained by ring opening polymerization (ROP) of CL and GL were synthesized with CL:GL ratios of 4:1; 10:1 and 20:1
Since the two groups share the same PUEt formulation, mechanical and morphological properties, we believe that the significant increase in the % of adipose tissue in PUEt + PLL + RG scaffolds is due to the local release of RG to the tissue colonizing the scaffold via specific activation of peroxisome proliferator–activated receptor γ (PPAR-γ) receptors
Summary
Process is one of the most challenging among connective tissues due to its structural and mechanical complexity and sensitivity to signals, such as the ones from hormone and nervous s ystems[10,11]. We addressed key factors impacting the biological performance of polyurethane-based crosslinked porous biomaterials as scaffolds for soft tissue regeneration, focusing the attention on the role of polymer chemistry and the m icroarchitecture[16,17,18] These findings enabled our group to develop 3D scaffolds with physicochemical and morphological properties guiding cell infiltration to the scaffold core and rapid recruitment of vascular tissue. By modifying the composition of polyester triol segments co-polymerized in the polyurethane network, we synthetized a gradient of Poly(Urethane-Ester-ether) PUEt porous scaffolds sharing similar physicochemical and morphological properties but displaying different substrate stiffnesses This experimental configuration allowed us to investigate the effects of mechanical cues on adipogenesis. The findings from this study are discussed in view of the emerging trends for developing implantable devices for adipose tissue regeneration with particular emphasis on breast reconstruction surgeries
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