CONICET | Buscador de Institutos y Recursos Humanos

After over 50 years of use in many biomedical applications, polyurethanes remain a popular choice due to their exceptional biocompatibility, mechanical properties and versatility. Polyurethane chemistry dictates the physico-chemical, mechanical, and biological properties of the resulting material and can be exploited to prepare a variety of materials including segmented polyurethane elastomers (SPU), rigid thermosets, adhesives, and foams. SPU are one of the most bio- and blood-compatible materials known today. These elastomers are block copolymers formed through step-growth polymerization by reacting a monomer containing at least two isocyanate functional groups with another monomer containing at least two hydroxyl (alcohol) groups in the presence of a catalyst. Properties such as durability, elasticity, fatigue resistance, compliance, and tolerance in the body, are often associated with polyurethanes. The unique and versatile mechanical properties of SPU elastomers are directly related to their two-phase microstructure, with hard domains acting as physically reversible crosslinking points, and soft domains that provide flexibility. The biostable or biodegradable character of SPU can be tailored. Thus, prolonged implantation requires materials with hydrolylic stability and oxidative-resistant soft segments (e.g., polycarbonate- or silicone-based polyurethanes), in combination with antioxidants or other additives. Bulk and surface modifications via hydrophilic/hydrophobic balance or by attachment of biorecognizable groups can also enhance the acceptance and healing of the implants. The mechanistic understanding gained in the pursuit of enhanced polyurethane biostability was recently applied to the development of a new class of bioresorbable materials. The development of bioresorbable and biocompatible SPU and polyurethane networks for temporary applications has received considerable interest in recent years. Optimal design of biodegradable polyurethane scaffolds should meet the following criteria: 1) biocompatibility and clearance of all degradation products with minimal inflammation, 2) independent control of biodegradation and mechanical properties, 3) system-responsive degradation. Depending on their mechanical properties, chemical composition and surface characteristics, degradable SPU can potentially be used in designing cardiovascular implants, drug delivery devices, non-adhesive barriers in trauma surgery, injectable augmentation materials and tissue adhesives. Nowadays, the applications of polyurethanes in tissue-organ regeneration scaffolds is an area of intensive research, and some examples are cardiovascular tissue engineering, artificial skin, nerve regeneration and musculoskeletal applications (articular cartilage repair, anterior cruciate ligament, knee joint meniscus, meniscal reconstruction, bone tissue engineering, smooth muscle cell constructs for contractile muscle). To date, most of the bioresorbable materials available for use in tissue engineering are hard, brittle substances best suited to bone and hard tissue applications. Several tissues that need to be replaced or regenerated, however, are soft tissues that require large elasticity. Thus, there is a need for synthetic degradable materials that exhibit the properties of elastic recoil and malleability. Segmental modifications of polyurethanes can be used to generate a library of polymers with broad structural diversity and derived properties. Tailoring the soft segment to achieve controlled degradation is a more common design strategy. To this end, a number of polyurethanes have been synthesized with hydrolytically unstable functional groups in the polymer backbone, typically poly(lactic acid), poly(glycolic acid), poly(å-caprolactone) and its copolymers. The synthesis of bioresorbable SPU requires a change from diisocyanates historically used in biostable formulations. Aromatic diisocyanates were often chosen for biomedical applications such as pacemaker lead coverings due to their enhanced mechanical properties. However, concerns that the degradation of these diisocyanates (i.e. 4,4'-methylenediphenyl diisocyanate, MDI) could generate potentially carcinogenic compounds (i.e. dianiline derivatives) has limited their translation to biodegradable polymers. Therefore, these aromatic diisocyanates were replaced with aliphatic diisocyanates such as L-lysine ethyl (or methyl) ester diisocyanate, hydrogenated MDI and hexamethylene diisocyanate that are more likely to have non-toxic degradation products. When appropriately designed, chain extenders are able to impart specific properties to the material. In this way, chain extenders are also investigated to promote highly ordered microphase-separated hard domains or to enhance hard segment degradation. The incorporation of urea-containing compounds or aromatic groups may increase hard segment cohesion by bidentate hydrogen bonding interactions or by p-bond stacking, respectively. In addition, the presence of hydrolyzable or enzyme sensitive linkages may modulate the degradative behaviour of hard domains. Bioresorbable polyurethanes have been shown to support the ingrowth of cells and undergo controlled degradation to non-cytotoxic decomposition products. These features combined with the tunable biological, mechanical, and physicochemical properties make these new materials excellent candidates for tissue engineering scaffolds. This presentation summarizes the recent advances and strategies in the synthesis of polyurethane systems, and its different applications in the medical field.