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Injectable hydrogels based on Schiff-base linkages as a promising platform for in situ drug delivery and tissue engineering

Valeria Caccamo

Injectable hydrogels based on Schiff-base linkages as a promising platform for in situ drug delivery and tissue engineering.

Rel. Gianluca Ciardelli, Roberta Pappalardo, Monica Boffito. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2022


Hydrogels have emerged as a promising alternative to overcome shortcomings that affect traditional biomedical treatments. They have gained increasing attention in the field of tissue engineering (TE) and drug delivery thanks to their high-water content, which provides a physiologically similar environment to the native extracellular matrix, and the capability of encapsulating and transferring their payload (e.g., drugs or biomolecules) to the surrounding tissues. Among the wide plethora of existing hydrogel platforms, hydrogels based on Schiff-base linkages possess favourable properties (e.g., high reactivity under mild conditions, stability under physiological conditions, self-healing ability, pH-responsiveness) that make them attractive to prepare injectable formulations. In this scenario, this thesis work aimed to design new in situ forming injectable hydrogels based on Schiff-base linkages exploiting the versatility of poly(urethane)s (PUs) as constituent materials for TE and drug delivery applications. For this purpose, two water-soluble PUs were successfully synthesized with suitable molecular weight and a huge number of functional groups (i.e., primary amines and aldehyde groups) to obtain hydrogels based on Schiff-base linkages. A high molecular weight PU, referred to as NHE3350 (Mn=24 kDa, D=1.7) was synthesized through a one-step synthesis process, starting from poly(ethylene glycol) (Mn 3350 Da) as diol, 1,6-hexamethylene diisocyanate as diisocyanate and N-Boc serinol as chain extender. NHE3350 was subjected to an acidic treatment to remove Boc protecting groups, thus exposing primary amines. The deprotected PU, referred to as SHE3350, exposed 6∙1019 -NH2 units/gPU, as quantified through the Ninhydrin and Orange II Sodium salt colorimetric assays. A low molecular weight aldehyde end-capped PU, referred to as AHE1500 (Mn=4 kDa, D=1.5) was synthesized through a two-step procedure, by reacting poly(ethylene glycol) (Mn 1500 Da), 1,6-hexamethylene diisocyanate and 4-hydroxybenzaldehyde. 2.5∙1020 -CHO units/gPU were quantified through UV-vis and Proton Nuclear Magnetic Resonance (1H NMR) spectroscopies. Hydrogels were prepared by mixing SHE3350 and AHE1500 aqueous solutions (15% w/V and 20% w/V polymer concentration, -NH2/-CHO 1:1 molar ratio). The formation of the Schiff-base linkages was assessed by analysing the infrared (IR) and the Carbon-13 solid-state NMR (13C ssNMR) spectra of the formed hydrogel, which showed new peaks ascribed to the imine bonds at 1645 cm-1 and at 156 ppm, respectively. Rheological characterization confirmed the formation of hydrogels with high resistance to applied strain. Swelling and stability tests in physiological-like conditions revealed that these hydrogels presented a high swelling ability (ca. 350% up to 21 days of incubation), while their degradation/dissolution rate was relatively low. Moreover, the study of the release profile of a model molecule (i.e., Fluorescein isothiocyanate dextran, FD4) showed a controlled and sustained release up to 21 days. Lastly, hydrogels exhibited easy injectability through a 21G needle and self-healing ability. The developed hydrogels are expected to enhance the therapeutic efficacy of local therapies, representing a breakthrough in drug/cell delivery, as well as in TE applications. In the future, the hydrogels will be loaded with different types of drugs/biomolecules, and with more complex systems, like nanoparticles for combined drug release, to prove the versatility of the designed therapeutic platform.

Relators: Gianluca Ciardelli, Roberta Pappalardo, Monica Boffito
Academic year: 2022/23
Publication type: Electronic
Number of Pages: 104
Additional Information: Tesi secretata. Fulltext non presente
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: New organization > Master science > LM-21 - BIOMEDICAL ENGINEERING
Aziende collaboratrici: UNSPECIFIED
URI: http://webthesis.biblio.polito.it/id/eprint/25798
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