Pieter J. Dijkstra

Phase separation processes in polymer solutions in relation to membrane formation

This review covers new experimental and theoretical physical research related to the formation of polymeric membranes by phase separation of a polymer solution, and to the morphology of these membranes. Two main phase separation processes for polymeric membrane formation are discussed: thermally induced phase separation and immersion precipitation. Special attention is paid to phase transitions like liquid-liquid demixing, crystallization, gelation, and vitrification, and their relation to membrane morphology. In addition, the mass transfer processes involved in immersion precipitation, and their influence on membrane morphology are discussed.

Cross-linking of dermal sheep collagen using a water-soluble carbodiimide

A cross-linking method for collagen-based biomaterials was developed using the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride (EDC). Cross-linking using EDC involves the activation of carboxylic acid groups to give O-acylisourea groups, which form cross-links after reaction with free amine groups. Treatment of dermal sheep collagen (DSC) with EDC (E-DSC) resulted in materials with an increased shrinkage temperature (Ts) and a decreased free amine group content, showing that cross-linking occurred. Addition of N-hydroxysuccinimide to the EDC-containing cross-linking solution (E/N-DSC) increased the rate of cross-linking. Cross-linking increased the Ts of non-cross-linked DSC samples from 56 to 73 degrees C for E-DSC and to 86 degrees C for E/N-DSC samples, respectively. For both cross-linking methods a linear relation between the decrease in free amine group content and the increase in Ts was observed. The tensile strength and the high strain modulus of E/N-DSC samples decreased upon cross-linking from 18 to 15 MPa and from 26 to 16 MPa, respectively. The elongation at break of E/N-DSC increased upon cross-linking from 142 to 180%.

Glutaraldehyde as a crosslinking agent for collagen-based biomaterials

The formation of Schiff bases during crosslinking of dermal sheep collagen (DSC) with glutaraldehyde (GA), their stability and their reactivity towards GA was studied. All available free amine groups had reacted with GA to form a Schiff base within 5 min after the start of the reaction under the conditions studied (0.5% (w/w) GA). Before crosslinks are formed the hydrolysable Schiff bases initially present were stabilized by further reaction with GA molecules. An increase in shrinkage temperature (Ts) from 56°C for non-crosslinked DSC (N-DSC) to 78°C for GA crosslinked DSC (G-DSC) was achieved after crosslinking for 1 h. From the relationship between the free amine group content and the Ts during crosslinking it was concluded that higher GA concentrations and longer reaction times will result in the introduction of pendant-GA-related molecules rather than crosslinks. After 24 h crosslinking an average uptake of 3 GA molecules per reacted amine group was found. No increase in the tensile strength of the materials was observed after crosslinking, which may be a result of formation of crosslinks within the fibres rather than in between fibres. Aligning of the fibres by applying a pre-strain to the samples and subsequent crosslinking yielded materials with an increased tensile strength.

[(salen)Al]‐Mediated, Controlled and Stereoselective Ring‐Opening Polymerization of Lactide in Solution and without Solvent: Synthesis of Highly Isotactic Polylactide Stereocopolymers from Racemic d,l‐Lactide

Easily accessible [(salen)(iPrO)Al] exerts excellent molecular-weight and stereochemical control in lactide polymerization either in solution or in the absence of solvent. The R,R initiator shows a marked preference for L-lactide over D-lactide. Stereoblock copolylactides with high melting points can be prepared directly from d,l-lactides by using a racemic initiator.

Single site catalysts for stereoselective ring-opening polymerization of lactides

Poly(lactide) (PLA) is the most well known biodegradable and biocompatible material among the aliphatic polyesters nowadays explored for biomedical, pharmaceutical and environmental applications. Different poly(lactide)s are distinguished, namely stereoregular PLLA and PDLA, atactic, heterotactic, syndiotactic and stereoblock PLAs. Because the stereochemistry of the monomeric units in the polymer chains plays a decisive role in the mechanical, physical and degradation properties of PLA materials, stereospecific catalysts to prepare different polylactide architectures are a major topic. In this review, after a general introduction on metal catalyzed ring opening polymerization, we mainly focus on single site catalyst systems inducing stereoselective polymerization of lactides.

Hydrogels in a historical perspective: From simple networks to smart materials

Over the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. Biomedical application of hydrogels was initially hindered by the toxicity of crosslinking agents and limitations of hydrogel formation under physiological conditions. Emerging knowledge in polymer chemistry and increased understanding of biological processes resulted in the design of versatile materials and minimally invasive therapies. Hydrogel matrices comprise a wide range of natural and synthetic polymers held together by a variety of physical or chemical crosslinks. With their capacity to embed pharmaceutical agents in their hydrophilic crosslinked network, hydrogels form promising materials for controlled drug release and tissue engineering. Despite all their beneficial properties, there are still several challenges to overcome for clinical translation. In this review, we provide a historical overview of the developments in hydrogel research from simple networks to smart materials.

Enzyme-catalyzed crosslinkable hydrogels: Emerging strategies for tissue engineering

State-of-the-art bioactive hydrogels can easily and efficiently be formed by enzyme-catalyzed mild-crosslinking reactions in situ. Yet this cell-friendly and substrate-specific method remains under explored. Hydrogels prepared by using enzyme systems like tyrosinases, transferases and lysyl oxidases show interesting characteristics as dynamic scaffolds and as systems for controlled release. Increased attention is currently paid to hydrogels obtained via crosslinking of precursors by transferases or peroxidases as catalysts. Enzyme-mediated crosslinking has proven its efficiency and attention has now shifted to the development of enzymatically crosslinked hydrogels with higher degrees of complexity, mimicking extracellular matrices. Moreover, bottom-up approaches combining biocatalysts and self-assembly are being explored for the development of complex nano-scale architectures. In this review, the use of enzymatic crosslinking for the preparation of hydrogels as an innovative alternative to other crosslinking methods, such as the commonly used UV-mediated photo-crosslinking or physical crosslinking, will be discussed. Photo-initiator-based crosslinking may induce cytotoxicity in the formed gels, whereas physical crosslinking may lead to gels which do not have sufficient mechanical strength and stability. These limitations can be overcome using enzymes to form covalently crosslinked hydrogels. Herewith, we report the mechanisms involved and current applications, focusing on emerging strategies for tissue engineering and regenerative medicine.

Melt block copolymerization of ε-caprolactone and L-lactide

AB block copolymers of e-caprolactone and (L)-lactide could be prepared by ring-opening polymerization in the melt at 110°C using stannous octoate as a catalyst and ethanol as an initiator provided e-caprolactone was polymerized first. Ethanol initiated the polymerization of e-caprolactone producing a polymer with e-caprolactone derived hydroxyl end groups which after addition of L-lactide in the second step of the polymerization initiated the ring-opening copolymerization of L-lactide. The number-average molecular weights of the poly(e-caprolactone) blocks varied from 1.5 to 5.2 × 103, while those of the poly(L-lactide) blocks ranged from 17.4 to 49.7 × 103. The polydispersities of the block copolymers varied from 1.16 to 1.27. The number-average molecular weights of the polymers were controlled by the monomer/hydroxyl group ratio, and were independent on the monomer/stannous octoate ratio within the range of experimental conditions studied. When L-lactide was polymerized first, followed by copolymerization of e-caprolactone, random copolymers were obtained. The formation of random copolymers was attributed to the occurrence of transesterification reactions. These side reactions were caused by the e-caprolactone derived hydroxyl end groups generated during the copolymerization of e-caprolactone with pre-polymers of L-lactide. The polymerization proceeds through an ester alcoholysis reaction mechanism, in which the stannous octoate activated ester groups of the monomers react with hydroxyl groups.

In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) cross-linked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide hydrochloride and N-hydroxysuccinimide (E/N-DSC) towards enzymatic degradation. Contrary to non-cross-linked DSC (N-DSC), which had a rate of weight-loss of 18.1% per hour upon degradation, no weight loss was observed for E/N-DSC during a 24 h degradation period. The tensile strength of the E/N-DSC samples decreased during this time period, resulting in partially degraded samples having 80% of the initial tensile strength remaining. The susceptibility of E/N-DSC samples towards enzymatic degradation could be controlled by varying the degree of cross-linking of the samples. Ethylene oxide sterilization of E/N-DSC samples made the material more resistant against degradation compared with non-sterilized E/N-DSC samples. This may be explained by a decrease of the adsorption of bacterial collagenase onto the collagen owing to reaction of ethylene oxide with remaining free amine groups in the collagen matrix.

Chiral Salan Aluminium Ethyl Complexes and Their Application in Lactide Polymerization

Synthetic routes to aluminium ethyl complexes supported by chiral tetradentate phenoxyamine (salan-type) ligands [Al(OC(6)H(2)(R-6-R-4)CH(2))(2){CH(3)N(C(6)H(10))NCH(3)}-C(2)H(5)] (4, 7: R=H; 5, 8: R=Cl; 6, 9: R=CH(3)) are reported. Enantiomerically pure salan ligands 1-3 with (R,R) configurations at their cyclohexane rings afforded the complexes 4, 5, and 6 as mixtures of two diastereoisomers (a and b). Each diastereoisomer a was, as determined by X-ray analysis, monomeric with a five-coordinated aluminium central core in the solid state, adopting a cis-(O,O) and cis-(Me,Me) ligand geometry. From the results of variable-temperature (VT) (1)H NMR in the temperature range of 220-335 K, (1)H-(1)H NOESY at 220 K, and diffusion-ordered spectroscopy (DOSY), it is concluded that each diastereoisomer b is also monomeric with a five-coordinated aluminium central core. The geometry is intermediate between square pyramidal with a cis-(O,O), trans-(Me,Me) ligand disposition and trigonal bipyramidal with a trans-(O,O) and trans-(Me,Me) disposition. A slow exchange between these two geometries at 220 K was indicated by (1)H-(1)H NOESY NMR. In the presence of propan-2-ol as an initiator, enantiomerically pure (R,R) complexes 4-6 and their racemic mixtures 7-9 were efficient catalysts in the ring-opening polymerization of lactide (LA). Polylactide materials ranging from isotactically biased (P(m) up to 0.66) to medium heterotactic (P(r) up to 0.73) were obtained from rac-lactide, and syndiotactically biased polylactide (P(r) up to 0.70) from meso-lactide. Kinetic studies revealed that the polymerization of (S,S)-LA in the presence of 4/propan-2-ol had a much higher polymerization rate than (R,R)-LA polymerization (k(SS)/k(RR)=10.1).