Matthieu Cuénoud
Articular cartilage is a soft tissue that covers the ends of articulating bones, and is essential for maintaining joint motion, i.e. translation and rotation between the bones. Articular cartilage nevertheless has a limited capacity for self-repair, and cartilage lesions following traumatic injury may consequently initiate an irreversible degenerative process. This ultimately leads to progressive loss of joint function, pain and medical costs. Many different clinical treatments have been investigated, but these have not so far led to satisfactory long-term solutions. Tissue engineering research has therefore focused on the preparation of synthetic bioresorbable scaffolds that provide a template for cells and guide the process of tissue regeneration. In the present study, it is proposed to develop an osteochondral scaffold using novel solvent-free processing methods based on supercritical carbon dioxide (CO2) foaming. The approach is first to tailor the mechanical properties of medical grade polylactides (PLA), using poly(ethylene glycol) (PEG) as a plasticizer, to produce scaffolds with reduced elastic moduli intended for cartilage repair. These polymer scaffolds are then combined with an existing biocomposite scaffold (PLLA/bioceramic), developed for bone repair, to give a bilayered scaffold suitable for osteochondral repair. The investigation thus covers: (I) the preparation of plasticized polylactide and the dependence of its properties on composition; (II) the design of processing windows for the production of porous plasticized polylactide scaffolds by supercritical CO2 foaming; (III) the preparation of hybrid structures with gradients in composition and properties, and tailored interfaces; (IV)the properties and in vitro response of sterilized scaffolds. Plasticization of semicrystalline poly-L-lactide (PLLA) with PEG reduces Tg to below 37 °C, depending on the composition, implying the amorphous regions to be in the rubbery state at body temperature. While immersion in an aqueous medium tends to promote phase separation in blends containing low molar mass PEG, relatively good stability is observed with PEG with a molar mass of 35,000 g/mol. It has thus been possible to prepare interconnected, open-pore foams with porosities of more than 75 %, cell diameters in the range 200 to 700 pm and compression moduli of a few MPa. It was also observed that addition of PEG resulted in foams with increased pore diameters and lower foam densities than the neat polylactide, but also increased pore coalescence at high saturation pressures, effects that were accounted for by the large decrease in melt viscosity on addition of PEG. Furthermore, the compression moduli of the foams were shown to be strongly reduced on addition of PEG, which was assumed to be a direct consequence of the plasticization of the polylactide by PEG and the accompanying decrease in glass transition temperature, implying the amorphous content to be in the rubbery state at in vivo temperature, as required. Thus, foams with moduli ranging from 0.3 to 15 MPa could be prepared from the different PLA/PEG blends and copolymers studied. Bilayered scaffolds were produced by assembling the plasticized foams with a biocomposite foam using an adapted fusion bonding method. This allowed control of interfacial properties such as the bonding strength, and the interface density and permeability. These hybrid scaffolds exhibited well-defined layers with suitable properties for the repair of bone and cartilage, respectively. Finally, X-ray and y irradiation was shown to strongly degrade the polymer matrix. However, it was found that treatment with ethylene oxide gas could be used to sterilize the scaffolds without significantly modifying their properties, or compromising their biocompatibility, as borne out by in vitro tests. The approach proposed in this work was hence concluded to be highly promising for cartilage repair, and the resulting hybrid osteochondral scaffolds are ready for the next stage of the developmental work, which will consist of extended in vivo studies.
EPFL2012
