A. J. Pennings

High molecular weight poly(L-lactide) and poly(ethylene oxide) blends: Thermal characterization and physical properties

Abstract The miscibility of high molecular weight poly( l -lactide) PLLA with high molecular weight poly(ethylene oxide) PEO was studied by differential scanning calorimetry. All blends containing up to 50 weight% PEO showed single glass transition temperatures. The PLLA and PEO melting temperatures were found to decrease on blending, the equilibrium melting points of PLLA in these blends decreased with increasing PEO fractions. These results suggest the miscibility of PLLA and PEO in the amorphous phase. Mechanical properties of blends with up to 20 weight% PEO were also studied. Changes in mechanical properties were small in blends with less than 10 weight% PEO. At higher PEO concentrations the materials became very flexible, an elongation at break of more than 500% was observed for a blend with 20 weight% PEO. Hydrolytic degradation up to 30 days of the blends showed only a small variation in tensile strength at PEO concentrations less than 15 weight%. As a result of the increased hydrophilicity, however, the blends swelled. Mass loss upon degradation was attributed to partial dissolution of the PEO fraction and to an increased rate of degradation of the PLLA fraction. Significant differences in degradation behaviour between PLLA/PEO blends and (PLLA/PEO/PLLA) triblock-copolymers were observed.

DEGRADATION OF AND TISSUE REACTION TO BIODEGRADABLE POLY(L-LACTIDE) FOR USE AS INTERNAL-FIXATION OF FRACTURES - A STUDY IN RATS

Samples of high-molecular-weight poly(L-lactide) (PLLA) (Mv = 9.0 x 10(5), a biomaterial developed for plates and screws used in internal fixation of jaw fractures, were implanted subcutaneously in the backs of rats to study tissue reaction to PLLA and to follow the degradation process. The PLLA seemed to follow the degradation pattern typical of biodegradable polyesters. After pure hydrolysis up to about 104 wk, phagocytic activity of macrophages was found at about 143 wk. Full resorption of PLLA was not demonstrated in this study. Except for the early and final parts of the implant period, no acute or chronic inflammatory reaction was observed. No implant was rejected. It is estimated that more than 3 yr will be required for total resorption of PLLA. For bone-healing this long period is of no practical importance. There is no need for removal of PLLA after fracture healing as is the case with metal fixation devices. Thus, PLLA has potential application in internal fixation of fractures and osteotomies in the maxillofacial region and other fractures that are not too heavily loaded in the human body.

Tissue ingrowth and degradation of two biodegradable porous polymers with different porosities and pore sizes.

Commonly, spontaneous repair of lesions in the avascular zone of the knee meniscus does not occur. By implanting a porous polymer scaffold in a knee meniscus defect, the lesion is connected with the abundantly vascularized knee capsule and healing can be realized. Ingrowth of fibrovascular tissue and thus healing capacity depended on porosity, pore sizes and compression modulus of the implant. To study the lesion healing potential, two series of porous polyurethanes based on 50/50 epsilon-caprolactone/L-lactide with different porosities and pore sizes were implanted subcutaneously in rats. Also, in vitro degradation of the polymer was evaluated. The porous polymers with the higher porosity, more interconnected macropores, and interconnecting micropores of at least 30 microm showed complete ingrowth of tissue before degradation had started. In implants with the lower macro-porosity and micropores of 10-15 microm degradation of the polymer occurred before ingrowth was completed. Directly after implantation and later during degradation of the polymer, PMN cells infiltrated the implant. In between these phases the foreign body reaction remained restricted to macrophages and giant cells. We can conclude that both foams seemed not suited for implantation in meniscal reconstruction while either full ingrowth of tissue was not realized before polymer degradation started or the compression modulus was too low. Therefore, foams must be developed with a higher compression modulus and more connections with sufficient diameter between the macropores.

In vivo degradation and biocompatibility study of in vitro pre-degraded as-polymerized polylactide particles

The degradation of high molecular weight as-polymerized poly(L-lactide) (PLLA) is very slow; it takes more than 5.6 yr for total resorption. Moreover, the degradation products of as-polymerized PLLA bone plates, consisting of numerous stable particles of high crystallinity, are related with a subcutaneous swelling in patients 3 yr postoperatively. In order to avoid these complications, polymers were developed that are anticipated to have comparable mechanical properties but a higher degradation rate and do not degrade into highly stable particles that can induce a subcutaneous swelling. On chemical grounds it can be expected that copolymerization of PLLA with 4% D-lactide (PLA96) or by modifying PLLA through cross-linking (CL-PLLA) will lead to less stable particles and a higher degradation rate. To evaluate the long-term suitability of these as-polymerized polymers, the biocompatibility of the degradation products should be studied. Considering the very slow degradation rate of as-polymerized PLLA, in vitro pre-degradation at elevated temperatures was used to shorten the in vivo follow-up periods. In this study, the biocompatibility and degradation of as-polymerized PLLA, PLA96 and CL-PLLA were investigated by implanting pre-degraded particulate materials subcutaneously in rats. Animals were killed after a postoperative period varying from 3 to 80 wk. Light and electron microscopical analysis and quantitative measurements were performed. The histological response of all three pre-degraded materials showed a good similarity with in vivo implanted material. Pre-degraded PLLA induced a mild foreign body reaction and showed a slow degradation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Preparation and properties of absorbable fibres from l-lactide copolymers

Abstract Absorbable fibres have been prepared from various copolymers of l -lactide with either d -lactide or ϵ-caprolactone. The lower crystallinity of these copolymers, compared with the homopolymer, is desirable in the light of their potential use as an absorbable suture material and has a pronounced effect on both preparation procedure and mechanical properties of these fibres. Due to the low crystallinity of the fibres, their mechanical properties are related to the structure of the amorphous phase, as is reflected by the effect of the glass transition temperature and molecular weight on tensile properties. By means of a dry spinning/hot drawing process, low crystalline fibres having strengths of 1 GPa could be prepared, whereas fibres prepared by melt spinning/hot drawing have strengths ranging from 0.19 for a completely amorphous copolymer to 0.53 GPa for the poly( l -lactide) homopolymer.

Use of porous polyurethanes for meniscal reconstruction and meniscal prostheses

In the past, porous materials made of an aromatic polyurethane (PU) were successfully used to meniscal reconstruction in dogs. Since aromatic PUs yield very toxic fragments upon degradation, a linear PU was synthesized by curing a poly(epsilon-caprolactone) and 1,4-trans-cyclohexane diisocyanate based prepolymer with cyclohexanedimethanol. Porous materials of this polymer were also implanted for meniscal reconstruction. The results were comparable with the most successful implant series so far. Additionally, a porous meniscal prosthesis was developed to replace a total meniscus. Due to the very high shear stresses to which the prosthesis would be exposed, the stress hysteresis phenomenon linear PUs are known to exhibit could be of great consequence. Therefore an aliphatic PU network, synthesized by cross-linking poly(epsilon-caprolactone) and 1,4-trans-cyclohexane diisocyanate with glycerol, was used. Dislocation caused by tearing out of the sutures was found to be a problem because the tear resistance of the material was relatively low. In this study the tearing problem has been partly circumvented by using a complex suturing technique. Meniscal prostheses turned out to induce fibrocartilage upon implantation, and degeneration of articular cartilage was less severe than after meniscectomy.

Polymerization temperature effects on the properties of l-lactide and ε-caprolactone copolymers

SummaryThe large difference in reactivity of L-lactide and ε-caprolactone in ring opening polymerization with stannous octoate, leads to the formation of copolymers with blocky structures. By varying the polymerization temperature, copolymers with different average sequence lengths and molecular weights can be synthesized. It is shown that the average monomer sequence length has a large effect on the thermal and mechanical properties of these copolymers.

High-strength poly(l-lactide) fibres by a dry-spinning/hot-drawing process

High-strength poly(l-lactide) (PLLA) fibres (tenacity 2.1 GPa, Youngs modulus 16 GPa) have been produced by dry spinning and subsequently hot drawing of PLLA (Mv = 9 × 105) from solutions in chloroform/toluene mixtures near the θ conditions where PLLA adopts an interrupted helical conformation. Ultimate fibre tenacity was dependent on drawability and final fibre cross section. Drawability improved with increasing heat of fusion, ΔHm, of the as-spun filaments, and was affected by the solvent composition, PLLA concentration in the spinning solution and preparation conditions. PLLA can exhibit an α-β crystal transition upon hot drawing. The theoretical strength of PLLA should amount to about 8 GPa as deduced from the diameter dependence of the tensile strength.

LONGITUDINAL GROWTH OF POLYMER CRYSTALS FROM FLOWING SOLUTIONS .3. POLYETHYLENE CRYSTALS IN COUETTE-FLOW

SummaryA detailed description is presented of several phenomena observed during the longitudinal growth of fibrillar polyethylene crystals from xylene solutions subjected to Couette flow. The rate at which the extended chain seed crystals grow longitudinally in this flow field could be established by measuring the increment in length of the macrofiber in a given period of time and also by finding the take-up speed under steady-state conditions which is equal to the growth rate.Continuous macrofibers of polyethylene with lengths of several hundred meters could be produced by this technique. The growth rate of the seed crystals anchored at a distance of approximately i mm from the surface of the rotating inner cylinder was found to increase linearly with the rotor speed, and these growth rate data agreed remarkably well with those values obtained in Poiseuille flow at corresponding local velocity gradients.Scanning electron micrographs reveal that these macrofibers, having diameter in the micron range, are composed of bundles of elementary fibrils of the Shish-Kebab type. It is believed that these Shish-Kebab backbones grow simultaneously by the action of the local flow field. The diameters of the macrofibers increase with the rotor speed as a result of branching of the backbone tips.The growth of seed crystals pushed against the rotor surface is considerably faster than the growth of seeds, around which the polymer solution flows freely. This fast growth is promoted by the roughness of the rotor surface and by the presence of methyl groups on the glass rotor surface introduced by silanization. These experimental observations suggest that the active element in this fast “surface-growth” is a layer of adsorbed polyethylene molecules on the rotor surface. By this surface-growth technique, continuous fibrillar crystallization appeared to be possible at a temperature of even 120.5 °C, which is well above the thermodynamic equilibrium temperature in a dilute p-xylene solution, and the longitudinal growth rate of the polyethylene macrofiber at this high temperature was still 6 cm/min.ZusammenfassungDieser Bericht enthält eine detaillierte Beschreibung verschiedener Vorgänge, die während des longitudinalen Wachstums von Polyäthylen-Faserkristallen aus Xylollösungen in einer Couette-Strömung beobachtet wurden. Die Geschwindigkeit mit der „extended-chain”-kristalline Keime in dieser Strömung longitudinal wachsen, konnte dadurch festgestellt werden, daß die Zunahme der Länge der Makrofaser innerhalb einer bestimmten Kristallisationszeit gemessen wurde und auch durch eine Messung der Wickelgeschwindigkeit, die der Wachstumgeschwindigkeit unter „steady-state”-Bedingungen entspricht.Kontinuierliche Makrofasern aus Polyäthylen mit einer Länge von mehreren hundert Metern konnten in dieser Weise hergestellt werden. Die Wachstumsgeschwindigkeit der kristallinen Keime, die in einer Entfernung von annähernd 1 mm von der Oberfläche des rotierenden Innenzylinders in die Lösung gebracht wurden, nahm, so stellte sich heraus, linear zu mit der Rührgeschwindigkeit. Diese Wachstumsgeschwindigkeitswerte stimmen auffallend überein mit den Werten, die in einer Poiseuille-Strömung unter denselben lokalen Geschwindigkeitsgradienten gefunden wurden.Rastermikroskopische Aufnahmen zeigen, daß diese Makrofasern, die Diameter in einer Größe einiger Mikron haben, aus Ansammlungen von elementaren Fibrillen der Schaschlik-Struktur aufgebaut sind. Man wäre geneigt anzunehmen, daß diese Schaschlik-Faserkerne alle zugleich wachsen unter dem Einfluß der lokalen Strömung. Die Diameter der Makrofasern nehmen mit der Rührgeschwindigkeit zu infolge einer Aufspaltung der Faserkernspitzen.Das Wachstum von kristallinen Keimen, die an die Oberfläche des Rührers gedrückt werden, ist bedeutend schneller als das Wachstum von Keimen, an denen die Polymerlösung frei vorbeiströmt. Dieses schnelle Wachstum wird gefördert durch die Rauheit der Oberfläche des Rührers und durch die Anwesenheit von Methylengruppen, die auf der gläsernen Rühreroberfläche durch Silanisierung angebracht wurden. Diese experimentellen Beobachtungen suggerieren, daß der wichtigste Faktor bei diesem Wachstum an der Oberfläche eine Schicht von Polyäthylenmolekülen ist, die an der Oberfläche des Rührers adsorbiert ist. Es stellte sich heraus, daß durch diese Technik das Wachsen faseriger Kristalle möglich ist bei einer Temperatur von 120,5 °C. Diese Temperatur geht sogar hinaus über die thermodynamische Gleichgewichtstemperatur in einer verdünnten Xylollösung. Die Geschwindigkeit des longitudinalen Wachstums von Polyäthylenmakrofasern bei dieser hohen Temperatur war noch 6 cm/min.

Light-microscopic and electron-microscopic evaluation of short-term nerve regeneration using a biodegradable poly(DL-lactide-epsilon-caprolacton) nerve guide

The aim of this study was to evaluate short-term peripheral nerve regeneration across a 10-mm. gap, using a biodegradable poly(DL-lactide-epsilon-caprolacton) nerve guide, with an internal diameter of 1.5 mm and a wall thickness of 0.30 mm. To do so, we evaluated regenerating nerves using light microscopy, transmission electron microscopy and morphometric analysis after implantation of 12-mm nerve guides in the sciatic nerve of the rat. Evaluation times ranged from 3-10 weeks. Three weeks after reconstruction, myelinated nerve fibers could be observed in the distal nerve stump. Ten weeks after reconstruction, the regenerating nerves already resembled normal nerves. In conclusion, we show that poly(DL-lactide-epsilon-caprolacton) nerve guides can be successfully applied in the reconstruction of severed nerves in the rat model. Furthermore, we have observed the fastest nerve regeneration described thus far, after reconstruction using a biodegradable nerve guide.