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ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków


Moura, Duarte (1. INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-180 Porto, Portugal; 2. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto,)


Development of degradable blood contacting devices (BCDs) is often associated not only with weak mechanical properties and high molecular weight of the degradation products, but also with long-term thrombogenicity issues. Poly(2-hydroxyethyl methacrylate) (pHEMA) emerges as a promising hydrogel to be used in BCDs mainly due to its bio/hemocompatibility and non-fouling character. However, aiming tissue engineering strategies, it is essential to overcome the lack of degradability presented by this hydrogel.
Thus, we aim to develop a degradable pHEMA (d-pHEMA) hydrogel to be used in a post-implantation tissue engineering approach, namely as BCDs. For that, a hydrolytically degradable crosslinking agent, pentaerythritol tetrakis(3-mercaptopropionate) (tetrakis) was copolymerized with pHEMA to allow its degradation, while oxidized graphene-based materials (GBMs) were explored as nanofillers to potentiate its mechanical performance. The hydrogel physicochemical and biological performance was evaluated, including in an in vivo rat subcutaneous implantation model (for the most promising conditions). In vitro results showed that inert and biocompatible pHEMA hydrogel was turned into a degradable material by incorporation of 0.25% (v/v) tetrakis. For higher tetrakis concentrations, low mechanical properties were achieved, ultimately not leading to film formation (>1% (v/v)). In situ addition of different GBM types allowed an improvement in the mechanical properties – 1wt% few-layer graphene oxide with 5 µm lateral size (M5ox) increased the ultimate tensile strength up to 0.2 MPa (4x higher than d-pHEMA) – and tuning of the in vitro degradation time in PBS, ranging from 2-4 months.
Notably, the intrinsic properties of pHEMA were kept, namely water uptake (» 60% of dry weight), wettability (» 40° contact angle) and short and long term cytocompatibility (24h and 6M extracts). The anti-adhesive properties were confirmed, with no adhesion of human umbilical vein endothelial cells to d-pHEMA nor d-pHEMA/GBMs hydrogels’ surface, after 1 and 7 days. Similarly, there is no platelet adhesion to the surface of the films. Such features are promising when envisioning the production BCDs, suggesting thrombus formation could be minimized.
Upon subcutaneous implantation of pHEMA, d-pHEMA and d-pHEMA/M5ox in inbred Sprague Dawley rats for 6M, no signs of inflammation or infection were observed at the implantation areas, with macroscopic photos confirming stability of pHEMA, and revealing a high degradation of the d-pHEMA (starting at 3M and almost complete after 6M). Contrarily, d-pHEMA/M5ox did not show significant degradation, in contrast with the in vitrodegradation results, which may be explained by a lower hydration and therefore, lower hydrolytic action when implanted.
The herein described newly developed degradable hydrogels have considerable potential as scaffolds for tissue engineering applications, with the greater amount of tetrakis leading to higher degradation. Depending on the envisioned application, increase of mechanical properties and delay of the degradation time can be modulated by the incorporation of few-layer graphene oxide. For example, d-pHEMA/M5ox are degradable, but keep their stability for at least 3 months, which suggests an appropriate timeframe for tissue regeneration in the vascular context.


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