RESUMEN
The history of resorbable polymers containing glycolide, lactide, ε-caprolactone and trimethylene carbonate, with a special emphasis being placed on the time frame of the 1960s-1990s is described. Reviewing the history is valuable when looking into the future perspectives regarding how and where these monomers should be used. This story includes scientific evaluations indicating that these polymers are safe to use in medical devices, while the design of the medical device is not considered in this report. In particular, we present the data regarding the tissue response to implanted polymers, as well as the toxicity and pharmacokinetics of their degradation products. In the translation of these polymers from "the bench to the bedside," various challenges have been faced by surgeons, medical doctors, biologists, material engineers and polymer chemists. This Perspective highlights the visionary role played by the pioneers, addressing the problems that occurred on a case by case basis in translational medicine.
Asunto(s)
Materiales Biocompatibles , Plásticos Biodegradables , Ensayo de Materiales , Materiales Biocompatibles/química , Materiales Biocompatibles/historia , Materiales Biocompatibles/farmacología , Plásticos Biodegradables/química , Plásticos Biodegradables/historia , Plásticos Biodegradables/farmacología , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
l-Lactide/trimethylene carbonate copolymers have been produced as multifilament fibers by high-speed melt-spinning. The relationship existing between the composition, processing parameters and physical properties of the fibers has been disclosed by analyzing how the industrial process induced changes at the macromolecular level, i.e., the chain microstructure and crystallinity development. A poly(l-lactide) and three copolymers having trimethylene carbonate contents of 5, 10 and 18 mol % were synthesized with high molecular weight ( Mn) up to 377 kDa and narrow dispersity. Their microstructure, crystallinity and thermal properties were dictated by the composition. The spinnability was then assessed for all the as-polymerized materials: four melt-spun multifilament fibers with increasing linear density were collected for each (co)polymer at a fixed take-up speed of 1800 m min-1 varying the mass throughput during the extrusion. A linear correlation resulted between the as-spun fiber properties and the linear density. The as-spun fibers could be further oriented, developing more crystallinity and improving their tensile properties by a second stage of hot-drawing. This ability was dependent on the composition and crystallinity achieved during the melt-spinning and the parameters selected for the hot-drawing, such as temperature, draw ratio and input speed. The crystalline structure evolved to a more stable form, and the degree of crystallinity increased from 0-52% to 25-66%. Values of tensile strength and Young's modulus up to 0.32-0.61 GPa and 4.9-8.4 GPa were respectively achieved.
Asunto(s)
Dioxanos/química , Poliésteres/química , Materiales Biocompatibles/química , Ensayo de Materiales , Polimerizacion , Relación Estructura-Actividad , Resistencia a la TracciónRESUMEN
Segmented poly(urethane urea)s (PUUs) with hard segments derived only from methyl 2,6-diisocyantohexanoate (LDI) without the use of a chain extender have previously been described. These materials, which contain hard segments with multiple urea linkages, show exceptionally high strain capability (1600-4700%). In the study reported here, the rate and effect of hydrolysis of these materials were determined for gamma-sterilized and nonsterilized samples. Materials investigated contained PCL, PTMC, P(TMC-co-CL), P(CL-co-DLLA), or P(TMC-co-DLLA) as soft segments and, as well as their mechanical properties, changes in mass, inherent viscosity (I.V.), and thermal properties were studied over 20 weeks. Results showed that the degradation rate was dependant on the soft segment structure, with a higher rate of degradation for the polyester-dominating PUUs exhibiting a substantial loss in I.V. A tendency of reduction of tensile strength and strain hardening was seen for all samples. Also, loss in elongation at break was detected, for PUU-P(CL-DLLA) it went from 1600% to 830% in 10 weeks. Gamma radiation caused an initial loss in I.V. and induced more rapid hydrolysis compared with nonsterilized samples, except for PUU-PTMC. A cytotoxicity test using human fibroblasts demonstrated that the material supports cell viability. In addition, an in vivo biocompatibility study showed a typical foreign body reaction after 1 and 6 weeks.
Asunto(s)
Materiales Biocompatibles/química , Poliuretanos/química , Urea/química , Animales , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Calor , Humanos , Hidrólisis , Masculino , Ensayo de Materiales , Ratas , Ratas Sprague-Dawley , Estrés Mecánico , Resistencia a la TracciónRESUMEN
Linear poly(urethane urea) containing a biodegradable soft segment and a hard segment built solely from methyl-2,6-diisocyanatehexanoate (LDI) is presented, using a procedure where no chain extender is required. By having LDI in excess, together with a soft segment, and adding water in the vapor phase continuously creates amines in situ resulting in hard segments containing multiple LDI units linked via urea linkages. As soft segments, polymers of trimethylene carbonate (TMC) and copolymers of TMC, epsilon-caprolactone, and D,L-lactic acid (DLLA) were used. High inherent viscosity, 0.95-1.65 dL/g, was afforded even when DLLA-containing soft segments were used, which usually undergo aminolysis. With a hard segment content between 12% and 18%, all of the materials showed very high elongation at breakage, ranging from 1600% to 4700%, and an elastic modulus from 2.1 to 140 MPa. This one-pot synthesis is simple and has now been shown to be applicable to a large number of systems.
Asunto(s)
Materiales Biocompatibles/química , Biodegradación Ambiental , Poliuretanos/química , Urea/química , Dioxanos/química , Elasticidad , Lactonas/química , Sustancias Macromoleculares , Espectroscopía de Resonancia Magnética , Modelos Químicos , Peso Molecular , Poliésteres , Polímeros/química , Presión , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura , Resistencia a la TracciónRESUMEN
The aim of this study was to examine the feasibility of using a new low-modulus biodegradable thermoplastic elastomer for in vivo application as a stent cover. The new polymer, a thermoplastic elastomer, consists of a three-armed co-polymer of poly(lactide)acid (PLLA), poly(trimethylene carbonate) (PTMC) and poly(caprolactone) (PCL). A degradation study was performed in a buffer solution at 37 degrees C for 4 and 6 weeks. The effect of degradation on mechanical properties was studied by stress-strain measurements and explained by using modulated DSC, GPC and mass measurements. A tapered block of PLLA and trimethylene carbonate connecting the crystalline outer part and the inner elastic part was highly susceptible to hydrolysis and caused rapid degradation and subsequent loss of mechanical properties. Random chain scission and homogenous hydrolysis resulted in a loss in mass and molecular weight. After 6 weeks of in vitro hydrolysis the molecular weight had decreased 54% and the elongation-at-break dropped from more than 300% to 90%. A medium free cell seeding study showed that endothelial cells adhered well to the polymeric material. An indicative animal study with the polymer acting as a stent cover showed very low levels of inflammation; however, pronounced neointima thickening was observed which was probably due to the premature failure of the material.