Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.

We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NP) with negative, positive and hydrophobic surfaces that were incorporated outside, inside or between the lipid bilayers, respectively. To characterize how NP are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NP are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 ºC with high enthalpy 34.8 J/g) avoiding the leakage of encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100 % of cellular uptake was achieved with a high cell survival (above 80 %), which is preserved (83 %) for doxorubicin loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 hour, leading to a cell survival reduction of 20 %. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating avoiding drug degradation. In conclusion, these drug loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place efficiently using an external AMF reducing or even eliminating side effects.

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