Microstructured poly(vinyl alcohol) hydrogels

Traditionally, treating a patient with a therapeutic has been done by systemic administration. Although this way of administration has proven successful in the fight against all kinds of diseases, recent developments aim for a more specialized and personalized administration to improve the medical care. This especially holds true for the administration of toxic compounds, which often result in severe side effects due to the systemic delivery distributing to both diseased and healthy tissue.

For drug delivery, natural and synthetic polymers are excellent candidates for the development of drug carriers and hereby offer a possible effective and convenient way to administer therapeutic compounds. A major advantage of polymer-based systems for drug delivery is the protection the polymeric carrier may provide keeping the active agent from premature degradation.

Hydrogel biomaterials based on poly(vinyl alcohol) (PVA) are attractive due to their biocompatibility and have a widespread history concerning biomedical applications.

A novel technique for the formation of physical PVA hydrogels is micro-transfer molding (µTM). This technique allows the formation of surface adhered microstructured hydrogels. Physical polymer interactions induce the stability within the three dimensional network.

 

Incorporation of the bioactive enzyme, β-glucuronidase, into these microstructured PVA hydrogels enables the in situ conversion of a benign prodrug into the active agent for controlled delivery directly at the site of cellular adhesion, a concept termed Substrate Mediated Enzyme Prodrug Therapy (SMEPT).

Another interesting characteristic of these biomaterials is the ability to control the mechanical properties, which is an important feature with regards to tissue engineering where biological tissues differ in stiffness. It has previously been shown that the stiffness of a material can have a profound effect on growth and proliferation of cells. Another interesting aspect of the mechanical properties of a biomaterial is mechano-transduction, which is the conversion of mechanical stimuli into a chemical or electrical response within the cell.

A common issue with PVA physical hydrogels is the inability to withhold small molecules within the polymer matrix. Composite hydrogels is one approach in the pursuance of controlling the loading of therapeutics. In short, a composite hydrogel contains different substances thus allowing for the incorporation of e.g. drug vesicles and thereby deceleration the release of therapeutic from the material. The optimal scenario is therefore developing substances, which do or do not interfere with the mechanical profile of the biomaterial all depending upon the application and needs of the system.