INVESTIGADORES
ABRAHAM Gustavo abel
congresos y reuniones científicas
Título:
The versatility of polyurethane chemistry: strategies to develop biomedical elastomers with enhanced properties
Autor/es:
G.A. ABRAHAM
Lugar:
Rosario, Santa Fé
Reunión:
Taller; 1º Taller de Órganos Artificiales, Biomateriales e Ingeniería de Tejidos (BIOOMAT); 2009
Institución organizadora:
UNR, CAIC y SLABO
Resumen:
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.