Poly(2-hydroxyethyl methacrylate) hydrogels containing graphene-based materials for blood-contacting applications: From soft inert to strong degradable material.

Degradable biomaterials for blood-contacting devices (BCDs) are associated with weak mechanical properties, high molecular weight of the degradation products and poor hemocompatibility. Herein, the inert and biocompatible FDA approved poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel was turned into a degradable material by incorporation of different amounts of a hydrolytically labile crosslinking agent, pentaerythritol tetrakis(3-mercaptopropionate). In situ addition of 1wt.% of oxidized graphene-based materials (GBMs) with different lateral sizes/thicknesses (single-layer graphene oxide and oxidized forms of few-layer graphene materials) was performed to enhance the mechanical properties of hydrogels. An ultimate tensile strength increasing up to 0.2 MPa (293% higher than degradable pHEMA) was obtained using oxidized few-layer graphene with 5 μm lateral size. Moreover, the incorporation of GBMs has demonstrated to simultaneously tune the degradation time, which ranged from 2 to 4 months. Notably, these features were achieved keeping not only the intrinsic properties of inert pHEMA regarding water uptake, wettability and cytocompatibility (short and long term), but also the non-fouling behavior towards human cells, platelets and bacteria. This new pHEMA hydrogel with degradation and biomechanical performance tuned by GBMs, can therefore be envisioned for different applications in tissue engineering, particularly for BCDs where non-fouling character is essential. STATEMENT OF SIGNIFICANCE: Suitable mechanical properties, low molecular weight of the degradation products and hemocompatibility are key features in degradable blood contacting devices (BCDs), and pave the way for significant improvement in the field. In here, a hydrogel with outstanding anti-adhesiveness (pHEMA) provides hemocompatibility, the presence of a degradable crosslinker provides degradability, and incorporation of graphene oxide reestablishes its strength, allowing tuning of both degradation and mechanical properties. Notably, these hydrogels simultaneously provide suitable water uptake, wettability, cytocompatibility (short and long term), no acute inflammatory response, and non-fouling behavior towards endothelial cells, platelets and bacteria. Such results highlight the potential of these hydrogels to be envisioned for applications in tissue engineered BCDs, namely as small diameter vascular grafts.