Preparation in supercritical CO2 of porous poly(methyl methacrylate)–poly(l-lactic acid) (PMMA–PLA) scaffolds incorporating ibuprofen (original) (raw)
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Journal of Materials Science, 2008
Supercritical carbon dioxide (SCCO 2) was used for the preparation of foamed sponges and intermingled fibers of biopolymers with potential applications in tissue engineering and drug delivery. The work was focused on the processing of both biodegradable polylactic acid (L-PLA) and non-biodegradable polymethylmethacrylate (PMMA) homopolymers. Monolithic porous sponges of amorphous PMMA were prepared using SCCO 2 as a porogen agent by simple swelling and foaming. Under similar experimental conditions, L-PLA was crystallized. The study also addresses the impregnation of biopolymers with an active agent dispersed in SCCO 2. The drug used for impregnation was triflusal, a platelet antiaggregant inhibitor for thrombogenic cardiovascular diseases. Foaming often leads to a closed pore structure after depressurization which is disadvantageous for 3D scaffolds as it does not fulfill the requirement of interconnectivity necessary for cell migration. To overcome these drawbacks, fibers forming macroporous structures were prepared using a semicontinuous antisolvent (SAS) technique.
Porous Biomaterials Obtained Using Supercritical CO 2 −Water Emulsions
Langmuir, 2007
Highly porous, hydrophilic porous matrices were fabricated by using a high internal phase supercritical-CO 2 (scCO 2 ) emulsion templating technique. The novel aspect of the work resides in the combination of a natural biopolymer (dextran) as the building component of the matrices and of an environmentally benign solvent (supercritical-CO 2 ) as the pore-generating phase. The synthetic route to the porous biomaterials involved the preliminary functionalization of the dextran chains with methacrylic moieties, formation of a scCO 2 -in-water concentrated emulsion, and curing of the external phase of the emulsion by radical polymerization. As the emulsion stabilizer a perfluoropolyether surfactant was chosen. The matrices obtained exhibit highly interconnected, trabecular morphologies. The porous biomaterial morphologies were qualitatively characterized by scanning electron microscopy (SEM) and the evaluation of void and interconnect sizes was carried out on the micrographs taken with the light microscope. To tailor the morphologies of the porous structures, the influence of the volume fraction of the internal phase and of the surfactant/ internal phase ratio was investigated. It was established that the variation of the volume fraction of the internal phase exerted only a limited influence on void and interconnect sizes. On the contrary the increase of surfactant concentration alters dramatically the distribution of void size, a large proportion of the void space enclosed within the matrix being attributable to voids with a diameter exceeding 100 µm. The free toxic solvent process of fabrication of the porous structures, the high water content, the expected biocompatibility, and the mechanical properties that resemble natural tissues make these porous hydrogels potentially useful for tissue engineering applications. Watson, M. S.; Whitaker, M. J.; Popov, V. K.; Davies, M. C.; Mandel, F. S.; Wang, J. D.; Shakesheff, K. M. Chem. Commun. (Cambridge) 2001, 109-110. (4) (a) Barbetta, A.; Dentini, M.; De Vecchis, M. S.; Filippini, P.; Formisano, G.; Caiazza, S. AdV. Funct. Mater. 2005, 15, 118-124. (b) Barbetta, A.; Dentini, M.; Zannoni, E. M.; De Stefano, M. E. Langmuir 2005, 15, 118-124. (c) Barbetta, A.; Dentini, M.; Massimi, M.; Conti Devirgiliis, L.
Journal of Drug Delivery Science and Technology, 2019
Poly(L-lactic acid) (PLLA) fibers were impregnated with the anti-inflammatory drug ketoprofen by supercritical CO 2 (scCO 2) assisted impregnation process, to develop drug-eluting absorbable sutures. This work indicates the possibility to tune not only the drug loading but also the release profile of ketoprofen from PLLA by modifying the impregnation (temperature and pressure) and depressurization (temperature and rate) conditions. Different PLLA sutures that release ketoprofen during 3 days up to 3 months were obtained. The release was shown to be governed by two parameters: the degradation rate of PLLA, that increases with the drug impregnation, and the sutures free volume, that was created due to scCO 2 sorbed and was partially conserved during depressurization. The degradation rate and the tensile strength loss of the suture are accelerated by ketoprofen since it catalyzes PLLA acid hydrolysis.
Journal of Porous Materials, 2008
Poly(ε-caprolactone) foams were prepared, via a batch process, by using supercritical CO 2 as foaming agent. Their porous structure was characterized through mercury porosimetry, helium and mercury pycnometry, scanning electron microscopy (SEM) and X-ray microtomography observations coupled with image analysis. The pore size distributions obtained by these two latter techniques show that the pore structure is more homogeneous when the foaming process is performed under a high CO 2 saturation pressure (higher than 250 bars).
Acta Biomaterialia, 2010
Porous scaffolds of a random co-polymer of x-pentadecalactone (PDL) and e-caprolactone (CL) (poly(PDL-CL)), synthesized by biocatalysis, were fabricated by supercritical carbon dioxide (scCO 2 ) foaming. The co-polymer, containing 31 mol.% CL units, is highly crystalline (T m = 82°C, DH m = 105 J g À1 ) thanks to the ability of the two monomer units to co-crystallize. The co-polymer can be successfully foamed upon homogeneous absorption of scCO 2 at T > T m . The effect of soaking time, depressurization rate and cooling rate on scaffold porosity, pore size distribution and pore interconnectivity was investigated by micro X-ray computed tomography. Scaffolds with a porosity in the range 42-76% and an average pore size of 100-375 lm were successfully obtained by adjusting the main foaming parameters.
European cells & materials
Tissue engineering scaffolds require a controlled pore size and structure to host tissue formation. Supercritical carbon dioxide (scCO2) processing may be used to form foamed scaffolds in which the escape of CO2 from a plasticized polymer melt generates gas bubbles that shape the developing pores. The process of forming these scaffolds involves a simultaneous change in phase in the CO2 and the polymer, resulting in rapid expansion of a surface area and changes in polymer rheological properties. Hence, the process is difficult to control with respect to the desired final pore size and structure. In this paper, we describe a detailed study of the effect of polymer chemical composition, molecular weight and processing parameters on final scaffold characteristics. The study focuses on poly(DL-lactic acid) (PDLLA) and poly(DL-lactic acid-co-glycolic acid) (PLGA) as polymer classes with potential application as controlled release scaffolds for growth factor delivery. Processing parameters...
Acta Biomaterialia, 2012
The porous structure of a scaffold determines the ability of bone to regenerate within this environment. In situations where the scaffold is required to provide mechanical function, balance must be achieved between optimizing porosity and maximizing mechanical strength. Supercritical CO 2 foaming can produce open-cell, interconnected structures in a low-temperature, solvent-free process. In this work, we report on foams of varying structural and mechanical properties fabricated from different molecular weights of poly(DL-lactic acid) PDLLA (57, 25 and 15 kDa) and by varying the depressurization rate. Rapid depressurization rates produced scaffolds with homogeneous pore distributions and some closed pores. Decreasing the depressurization rate produced scaffolds with wider pore size distributions and larger, more interconnected pores. In compressive testing, scaffolds produced from 57 kDa PDLLA exhibited typical stress-strain curves for elastomeric open-cell foams whereas scaffolds fabricated from 25 and 15 kDa PDLLA behaved as brittle foams. The structural and mechanical properties of scaffolds produced from 57 kDa PDLLA by scCO 2 ensure that these scaffolds are suitable for potential applications in bone tissue engineering.
A supercritical CO2 injection system for the production of polymer/mammalian cell composites
The Journal of Supercritical Fluids, 2008
We have recently described a technique whereby supercritical CO 2 (scCO 2 ) was used to process mammalian cells into polymeric tissue engineering scaffolds. However, the time-dependent survival of the cells in scCO 2 places significant restrictions on polymer processing times and pressures, which are both important factors in the final characteristics of the foamed scaffold. Here, we report an extension to that work that facilitates adequate plasticization time followed by the introduction of cells into the already plasticized polymer via a high-pressure CO 2 injection port. Live murine C2C12 cells were shown to not only survive this injection process, via LIVE/DEAD staining, but also to retain their ability to undergo osteogenic differentiation after induction with bone morphogenetic protein-2 (BMP-2) as indicated by an alkaline phosphatase activity. Cells were injected into plasticized poly(DL-lactic acid) (P DL LA) under scCO 2 conditions and were visualised in the resultant 3D porous foams by both SEM and micro-CT. After subsequent culture of the cell loaded scaffolds, the cells were shown to retain both metabolic and enzyme activity. This work represents an important development in the production of polymer/cell composite materials for biotechnological applications using a single scCO 2 processing step.
Biomaterials, 1996
A novel method was developed to produce highly porous sponges for potential use in tissue engineering, without the use of organic solvents. Highly porous sponges of biodegradable polymers are frequently utilized in tissue engineering both to transplant cells or growth factors, and to serve as a template for tissue regeneration. The processes utilized to fabricate sponges typically use organic solvents, but organic residues remaining in the sponges may be harmful to adherent cells, protein growth factors or nearby tissues. This report describes a technique to fabricate macroporous sponges from synthetic biodegradable polymers using high pressure carbon dioxide processing at room temperature. Solid discs of poly (D,L-lactic-co-glycolic acid) were saturated with COP by exposure to high pressure CO1 gas (5.5 MPa) for 72 h at room temperature. The solubility of the gas in the polymer was then rapidly decreased by reducing the CO* gas pressure to atmospheric levels. This created a thermodynamic instability for the CO2 dissolved in the polymer discs, and resulted in the nucleation and growth of gas cells within the polymer matrix. Polymer sponges with large pores (approximately 100 pm) and porosities of up to 93% could be fabricated with this technique. The porosity of the sponges could be controlled by the preform production technique, and mixing crystalline and amorphous polymers. Fibre-reinforced foams could also be produced by placing polymer fibres within the polymer matrix before CO2 gas processing. 0 1996 Elsevier Science Limited