Biomedical subjects

Thomas Freier

Publications and source records attributed to Thomas Freier.

8 recordsLinked to original sources

PubMed2006

In vitro and in vivo studies on blends of isotactic and atactic poly (3-hydroxybutyrate) for development of a dura substitute material.

Blends of semicrystalline isotactic poly(3-hydroxybutyrate) (PHB) with amorphous atactic PHB (at-PHB) were prepared by solution-casting using 30%, 50% and 70% at-PHB, and were studied for medical applications. The mechanical properties of the blends including the elastic modulus and elongation at break are strongly affected by the blend composition. The elastic modulus decreases with increasing fraction of at-PHB in the blend from 3350 MPa in the case of PHB to 170 MPa of PHB/at-PHB (30/70). In contrast, the elongation at break increases from 2% in pure PHB up to 50% in the case of the blend with 70% at-PHB. The in vitro degradation is changed as well. The molecular weight of PHB/at-PHB (30/70) is reduced to 5% after 2 years storage in phosphate buffer compared to 35% for pure PHB stored at identical conditions. The in vitro cell vitality is slightly reduced depending on the composition. PHB/at-PHB blends with 30% and 50% at-PHB were selected as dura substitute in minipigs based on the results of the in vitro investigation and the mechanical testing. Patch films with a structured surface on one side were fabricated by a dipping-leaching method. Dura defects were clinically and histologically examined 3, 6, and 9 months after implantation, confirming defect closure, prevention of adhesions to brain tissue, and no signs of inflammation or malignant degeneration. The PHB-based patch materials fulfill the requirements which are necessary for a dura substitute.

3-Hydroxybutyric Acid↗

PubMed2005

Coil-reinforced hydrogel tubes promote nerve regeneration equivalent to that of nerve autografts.

Despite spontaneous sprouting of peripheral axons after transection injury, peripheral regeneration is incomplete and limited to short gaps, even with the use of autograft tissue, which is considered to be the "gold" standard. In an attempt to obviate some of the problems associated with autografts, including limited donor tissue and donor site morbidity, we aimed to synthesize a synthetic nerve guidance channel that would perform as well as the nerve autograft. Given that the patency of the nerve guidance channel is critical for repair, we investigated a series of nerve guidance channel designs where patency and the resulting regenerative capacity were compared in a transected rat sciatic nerve injury model. Three tube designs were compared to autograft tissue: plain, corrugated and coil-reinforced tubes of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate). Of the three designs, the coil-reinforced tubes demonstrated superior performance in terms of patency. By electrophysiology and histomorphometry, the coil-reinforced tubes demonstrated outcomes that were comparable to autografts after both 8 and 16 weeks of implantation. The nerve action potential (NAP) velocity and muscle action potential (MAP) velocity for the coil-reinforced PHEMA-MMA tube was 54.6+/-10.1 and 10.9+/-1.3 m/s, respectively at 16 weeks, which was statistically equivalent to those of the autograft at 37.5+/-7.9 and 11.3+/-2.0 m/s. The axon density in the coil-reinforced tube was 2.16+/-0.61x10(4) axons/mm2, which was statistically similar to that of the autograft of 2.41+/-0.62x10(4) axons/mm2 at 16 weeks. These coil-reinforced tubes demonstrated equivalence to autografts for nerve regeneration, demonstrating the importance of channel design to regenerative capacity and more specifically the impact of patency to regeneration.

Action Potentials↗

PubMed2005

Controlling cell adhesion and degradation of chitosan films by N-acetylation.

As part of our ongoing effort to develop a biodegradable nerve guidance channel based on chitin/chitosan, we conducted a systematic in vitro study on the biodegradation and neural cell compatibility of chitosan and N-acetylated chitosan. The in vitro degradation (pH 7.4, 37 degrees C) in the presence of 1.5 microg/ml lysozyme showed a progressive mass loss to greater than 50% within 4 weeks for films with 30-70% acetylation. In contrast, the degradation of samples with very low or high acetylation was minimal over the 4-week period. Neural cell compatibility of chitosan and N-acetylated chitosan was tested using primary chick dorsal root ganglion (DRG) neurons. All chitosan-based films showed DRG cell adhesion after 2 days of culture. However, cell viability decreased with increasing acetylation. Chitosan that was 0.5% acetylated had the greatest cell viability, which was approximately 8 times higher than that of chitosan that was 11% acetylated. Chitosan with 0.5% and 11% acetylation showed more and longer neurites than the other samples studied. Thus chitosan amine content can be tuned for optimal biodegradation and cell compatibility, which are important for tissue engineering in the nervous system.

Acetylation↗

PubMed2005

Chitin-based tubes for tissue engineering in the nervous system.

The purpose of this study was to investigate chitin and chitosan as potential materials for biodegradable nerve guides. Transparent chitin hydrogel tubes were synthesized, for the first time, from chitosan solutions using acylation chemistry and mold casting techniques. Alkaline hydrolysis of chitin tubes resulted in chitosan tubes, with the extent of hydrolysis controlling the resulting amine content. This, in turn, impacted compressive strength and cell adhesion. Chitosan tubes were mechanically stronger than their chitin origins, as measured by the transverse compressive test, where tubes having degrees of acetylation of 1%, 3%, 18% (i.e. chitosan) and 94% (i.e. chitin) supported loads at a 30% displacement of 40.6 +/- 4.3, 25.3 +/- 4.5, 10.6 +/- 0.8, and 8.7 +/- 0.4 g, respectively. However, the chitin processing methodology could be optimized for compressive strength, by either incorporating reinforcing coils in the tube wall, or air-drying the hydrogel tubes. Chitin and chitosan supported adhesion and differentiation of primary chick dorsal root ganglion neurons in vitro. Chitosan films showed significantly enhanced neurite outgrowth relative to chitin films, reflecting the dependence of nerve cell affinity on the amine content in the polysaccharide: neurites extended 1794.7 +/- 392.0 microm/mm(2) on chitosan films vs. 140.5 +/- 41.6 microm/mm(2) on chitin films after 2 days of culture. This implies that cell adhesion and neurite extension can be adjusted by amine content, which is important for tissue engineering in the nervous system. The methods for easy processing and modification of chitin and chitosan described herein, allow the mechanical properties and cyto-compatibility to be controlled and provide a means for a broader investigation into their use in biomedical applications.

Animals↗

PubMed2005

Synthesis of degradable poly(L-lactide-co-ethylene glycol) porous tubes by liquid-liquid centrifugal casting for use as nerve guidance channels.

Biodegradable nerve guidance channels are advantageous, obviating the need for their removal after regeneration; however, most channels lack the appropriate mechanical properties for soft tissue implantation and/or degrade too quickly, resulting in reduced regeneration and necessitating the need for the design of polymers with tunable degradation profiles and mechanical properties. We designed a series of biodegradable polymeric hydrogel tubes consisting of L-lactide (LLA) and polyethylene glycol (PEG) where both the ratio of LLA to PEG and PEG molar mass were varied. By adjusting the PEG:LLA ratio and the molecular weight of the PEG oligomer we were able to control degradation and mechanical properties of our polymers. By incorporating methacrylate (MA) groups on both termini of the linear oligomers, porous tubes were synthesized by a redox-initiated free radical mechanism during a liquid-liquid centrifugal casting process. The tube wall had a bead-like morphology, as determined by SEM, which was reminiscent of previous porous hydrogel tubes synthesized by the same method. Tubes swelled with degradation to 160 vol%, or 640 wt%, and an increased radius calculated at 1.26 times. Those tubes with greater PEG content and PEG molar mass degraded faster than those with greater LLA content, as was expected. Interestingly, the wall morphology changed with degradation to a fiber-like structure and the mechanical properties decreased with degradation. By correlating the accelerated degradation study to a physiologic one, these porous hydrogel tubes were stable for an equivalent of 1.5 months, after which the mechanical properties began to deteriorate. This study demonstrates how porous hydrogel tubes can be designed to meet tissue regeneration criteria by tuning the formulation chemistry and specifically how the ratio of hydrophobic/crystalline LLA and hydrophilic/amorphous PEG impact tube properties.

Absorbable Implants↗

PubMed2003

Surface modification of tricalcium phosphate for improvement of the interfacial compatibility with biodegradable polymers.

The surface of tricalcium phosphate (TCP) filler particles was activated by treatment with dilute aqueous phosphoric acid. ATR-IR spectra indicated the formation of calcium hydrogen phosphate dihydrate at the surface. Oligo(lactone)s were formed by the subsequent reaction of the activated TCP with L-lactide and epsilon -caprolactone, respectively, at 150 degrees C without any additional catalysts. After extraction of the oligo(lactide), the residue of modified TCP-included calcium lactate whereas the water of crystallization of the dihydrate disappeared as shown by ATR-IR spectroscopy. Owing to the insolubility of TCP in common solvents, the analogous reaction between water-soluble disodium hydrogen phosphate dihydrate and L-lactide was used to study the kind of chemical bonds by high-resolution NMR spectroscopy. The 1H and 13C NMR spectra of the reaction product also pointed out the presence of calcium lactate. Additionally, signals were found indicating a covalent attachment of lactic acid units onto the phosphorus. For the preparation of composites, poly(L,DL-lactide) was mixed with TCP and modified TCP, respectively, in a ratio of 75/25 (w/w) and directly injection moulded into tensile test specimens at a barrel temperature of 180 degrees C. Although mechanical properties were not improved, scanning electron microscopy (SEM) indicated a better interfacial phase interaction in the composite with the modified TCP. Chemical bonds between filler and polymer matrix are assumed to be formed by transesterification reactions.

Biocompatible Materials↗

PubMed2002

In vitro and in vivo degradation studies for development of a biodegradable patch based on poly(3-hydroxybutyrate).

For the development of a resorbable gastrointestinal patch, the in vitro degradation of solution-cast films of poly(3-hydroxybutyrate) (PHB), modifications of PHB expected to influence its degradation time, as well a poly(L-lactide) (PLLA) was examined. The molecular weight of pure PHB decreased by one-half after 1 year in buffer solution (pH 7.4, 37 degrees C). Acceleration in molecular weight decrease was observed by blending with atactic PHB, whereas no influence was found with low-molecular weight PHB. Leaching of a water-soluble additive led to a slight acceleration of PHB degradability. In contrast, a deceleration in degradation rate was observed with the addition of a hydrophobic plasticizer. In vitro tests indicated an accelerating effect of pancreatin on PHB degradation, whereas PLLA degradation remained essentially uninfluenced. In comparison to simple hydrolysis, the degradation rate of PHB was accelerated about threefold. From the in vitro results, a PHB/atactic PHB blend was selected for repair of a bowel defect in Wistar rats. A patch film was fabricated by a dipping/leaching method. Twenty-six weeks post-implantation, material remnants were found in only one of four animals. The bowel defects were closed in all cases. It could be assessed that the patch material resists the intestinal secretions for a sufficiently long time but that it finally degrades completely.

Animals↗

PubMed2002

Anti-inflammatory prodrugs as plasticizers for biodegradable implant materials based on poly(3-hydroxybutyrate).

Salicylic and acetylsalicylic acid esters were tested as plasticizers for biodegradable poly(3-hydroxybutyrate) (PHB). The aim is the combination of plasticizing and anti-inflammatory properties in the fabrication of implant materials. Solution-cast films made of mixtures of PHB and 30% ester showed plasticization accompanied by a decrease of elastic modulus and an increase in elongation at break in comparison with pure PHB films. However, the number of usable plasticizers from the group of the salicylic acid and acetylsalicylic acid esters is limited. Short-chain derivatives are volatile while long-chain compounds tend to crystallize. In both cases PHB films embrittle within short time. Moreover, some derivatives show a fast release in an aqueous environment. As alternative nonsteroidal anti-inflammatory prodrugs arylpropionic acid esters were tested as plasticizers. The addition of ketoprofen ethyl ester led to PHB films with decreased brittleness. In summary, various esters of anti-inflammatory drugs show plasticizing effects on solution-cast PHB films comparable with those of commonly used citric acid esters.

Journal Article↗