Arend Jan Schouten

Replacement of the Knee Meniscus by a Porous Polymer Implant A Study in Dogs

Background Meniscectomy will lead to articular cartilage degeneration in the long term. Therefore, the authors developed an implant to replace the native meniscus. Hypothesis The porous polymer meniscus implant develops into a neomeniscus and protects the cartilage from degeneration. Study Design Controlled laboratory study. Methods In a dog model, a porous polymer scaffold with optimal properties for tissue infiltration and regeneration of a neomeniscus was implanted and compared with total meniscectomy. The tissue infiltration and redifferentiation in the scaffold, the stiffness of the scaffold, and the articular cartilage degeneration were evaluated. Results Three months after implantation, the implant was completely filled with fibrovascular tissue. After 6 months, the central areas of the implant contained cartilage-like tissue with abundant collagen type II and proteoglycans in their matrix. The foreignbody reaction remained limited to a few giant cells in the implant. The compression modulus of the implant-tissue construct still differed significantly from that of the native meniscus, even at 6 months. Cartilage degeneration was observed both in the meniscectomy group and in the implant group. Conclusion The improved properties of these polymer implants resulted in a faster tissue infiltration and in phenotypical differentiation into tissue resembling that of the native meniscus. However, the material characteristics of the implant need to be improved to prevent degeneration of the articular cartilage. Clinical Relevance The porous polymer implant developed into a polymer-tissue construct that resembled the native meniscus, and with improved gliding characteristics, this prosthesis might be a promising implant for the replacement of the meniscus.

Effect on tissue differentiation and articular cartilage degradation of a polymer meniscus implant - A 2-year follow-up study in dogs

Background Replacement of the meniscus by an implant could potentially avoid cartilage degeneration. Hypothesis An implant of degradable polycaprolacton-polyurethane should act as a temporary scaffold enabling regeneration of a new meniscus by slow degradation of the polymer and simultaneous in-growth and differentiation of tissues into the typical cartilage-like tissue of the meniscus. Study Design Controlled laboratory study. Methods In 13 dogs’ knees, the lateral meniscus was replaced with a porous polymer implant (6 and 7 for 6- and 24-month follow-up, respectively); in 7 knees only a meniscectomy was performed. In 6 knees, no surgery was performed. After 6 and 24 months, the implants and the articular cartilage were histologically evaluated. Compression-stress tests were performed on implant biopsy specimens. Results The implants were fully integrated into the tissue without formation of a capsule. The foreign body reaction did not exceed grade I. Differentiation from fibrous- to cartilage-like tissue was pronounced after 24 months. Viable cells were particularly absent after 24 months in central parts of the most anterior part of the scaffold. The mechanical properties of the implants were intermediate between the scaffold before implantation and native meniscus tissue and were not different between 6 and 24 months. After both 6 and 24 months, small areas of the implant were not covered with tissue. Cartilage degeneration was not prevented. Conclusion A final remodeling of tissue into neomeniscus tissue could not take place since the original structure of the polymer was still present after 24 months. The implant did not prevent cartilage degradation. Several factors are discussed that may be responsible for this. Clinical Relevance Although clinical application of a polymer implant for the replacement of the entire meniscus is not supported by this study, the authors strongly believe in the concept, but further improvements in the implant and surgical technique are needed before such an implant can be recommended for human clinical use.

GRAFTING KINETICS OF POLY(METHYL METHACRYLATE) ON MICROPARTICULATE SILICA

Abstract Grafting of poly(methyl methacrylate) (PMMA) on microparticulate silica was achieved by initiating the polymerization of MMA by 4,4′-azobis(4-cyanopentanoic acid) that was covalently bound to the silica surface. The initiator seems to be destabilized upon binding it to the silica surface. The kinetics of the graft polymerization are described and are largely affected by the Trommsdorff effect, which makes it possible to graft a high amount of PMMA on silica.

Polyacrylamide brush coatings preventing microbial adhesion to silicone rubber

Silicone rubber is a frequently used biomaterial in biomedical devices and implants, yet highly prone to microbial adhesion and the development of a biomaterial-centered infection. Effective coating of silicone rubber to discourage microbial adhesion has thus far been impossible due to the hydrophobic character of its surface, surface deterioration upon treatment and instability of coatings under physiological conditions. Here we present a method to successfully grow polyacrylamide (PAAm) brushes from silicone rubber surfaces after removal of low molecular weight organic molecules (LMWOM), such as silane oligomers. PAAm brush coating did not cause any surface deterioration and discouraged microbial adhesion, even after 1-month exposure to physiological fluids. The method presented opens many new avenues for the use of silicone rubber as a biomaterial, without the risk of developing a biomaterial-centered infection.

Polyurethane scaffold formation via a combination of salt leaching and thermally induced phase separation.

Porous scaffolds have been made from two polyurethanes based on thermally induced phase separation of polymer dissolved in a DMSO/water mixture in combination with salt leaching. It is possible to obtain very porous foams with a very high interconnectivity. A major advantage of this method is that variables like porosity, pore size, and interconnectivity can be independently adjusted with the absence of toxic materials in the production process. The obtained compression moduli were between 200 kPa and 1 MPa with a variation in porosity between 76 and 84%. Currently the biological and medical aspects are under evaluation.

Anionic grafting of polystyrene and poly(styrene-block-isoprene) onto microparticulate silica and glass slides

Polystyrene and poly(styrene-block-isoprene) were grafted onto microparticulate silica by initiating immobilized double bonds at the silica surface with t-butyllithium, and subsequently adding monomer to the reaction suspension. Grafted block copolymers could be synthesized by adding a second monomer after the first monomer had reacted completely. The obtained molecular-weight distributions were somewhat broader than those for comparable anionic homopolymerizations.

Considerations in binding diblock copolymers on hydrophilic alginate beads for providing an immunoprotective membrane.

Alginate-based microcapsules are being proposed for treatment of many types of diseases. A major obstacle however in the successes is that these capsules are having large lab-to-lab variations. To make the process more reproducible, we propose to cover the surface of alginate capsules with diblock polymers that can form polymer brushes. In the present study, we describe the stepwise considerations for successful application of diblock copolymer of polyethylene glycol (PEG) and poly-l-lysine (PLL) on the surface of alginate beads. Special procedures had to be designed as alginate beads are hydrophilic and most protocols are designed for hydrophobic biomaterials. The successful attachment of diblock copolymer and the presence of PEG blocks on the surface of the capsules were studied by fluorescence microscopy. Longer time periods, that is, 30–60 min, are required to achieve saturation of the surface. The block lengths influenced the strength of the capsules. Shorter PLL blocks resulted in less stable capsules. Adequate permeability of the capsules was achieved with poly(ethylene glycol)-block-poly(l-lysine hydrochloride) (PEG454-b-PLL100) diblock copolymers. The capsules were a barrier for immunoglobulin G. The PEG454-b-PLL100 capsules have similar mechanical properties as PLL capsules. Minor immune activation of nuclear factor κB in THP-1 monocytes was observed with both PLL and PEG454-b-PLL100 capsules prepared from purified alginate. Our results show that we can successfully apply block copolymers on the surface of hydrophilic alginate beads without interfering with the physicochemical properties.

Polymer-filler interactions in poly(vinyl chloride) filled with glass beads: effect of grafted poly(methyl methacrylate)

Adhesion between filler and matrix has been studied using a model system composed of glass bead filled poly(vinyl chloride) (PVC). Stress-strain and volume-strain tests and scanning electron microscopy revealed that adhesion is improved by grafting poly(methyl methacrylate) (PMMA), which is known to be miscible with the PVC matrix, upon the surface of the glass beads. The best results were obtained when large amounts of grafted PMMA were used, leading to maximum stress of the composite, nearly as high as that of pure PVC.

END-GRAFTING OF (CO)POLYGLUTAMATES AND (CO)POLYASPARTATES ONTO SI-OH CONTAINING SURFACES

(Co)polyglutamates and (co)polyaspartates were grafted onto microparticulate silica and flat Si-OH containing surfaces, by initiating the N-carboxyl anhydrides of the corresponding α-amino acids with an immobilized primary amine. The copolymers were prepared by polymerization of mixtures of N-carboxy anhydrides. In the case of microparticulate silica, all the available monomer was converted into grafted polymer, whereas in the case of flat surfaces, non-grafted material was formed as well. The grafted products were identified with infra-red spectroscopy and X-ray photoelectron spectroscopy.

Synthesis and Phase Behavior of Poly(N-isopropylacrylamide)-b-Poly(L-Lysine Hydrochloride) and Poly(N-Isopropylacrylamide-co-Acrylamide)-b-Poly(L-Lysine Hydrochloride)

The synthesis of poly(N-isopropylacrylamide)-b-poly(L-lysine) and poly(N-isopropylacrylamide-co-acrylamide)-b-poly(L-lysine) copolymers was accomplished by combining atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP). For this purpose, a di-functional initiator with protected amino group was successfully synthetized. The ATRP of N-isopropylacrylamide yielded narrowly dispersed polymers with consistent high yields (~80%). Lower yields (~50%) were observed when narrowly dispersed random copolymers of N-isopropylacrylamide and acrylamide where synthesized. Amino-terminated poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide-co-acrylamide) were successfully used as macroinitiators for ROP of N6-carbobenzoxy-L-lysine N-carboxyanhydride. The thermal behavior of the homopolymers and copolymers in aqueous solutions was studied by turbidimetry, dynamic light scattering (DLS) and proton nuclear magnetic resonance spectroscopy (1H-NMR).