Systematic selection of solvents for the fabrication of 3D combined macro- and microporous polymeric scaffolds for soft tissue engineering

In this study, we investigate the fabrication of 3D porous poly(lactic-co-glycolic acid) (PLGA) scaffolds using the thermally-induced phase separation technique. The current study focuses on the selection of alternative solvents for this process using a number of criteria, including predicted solubility, toxicity, removability and processability. Solvents were removed via either vacuum freeze-drying or leaching, depending on their physical properties. The residual solvent was tested using gas chromatography-mass spectrometry. A large range of porous, highly interconnected scaffold architectures with tunable pore size and alignment was obtained, including combined macro- and microporous structures and an entirely novel 'porous-fibre' structure. The morphological features of the most promising poly(lactic-co-glycolic acid) scaffolds were analysed via scanning electron microscopy and X-ray micro-computed tomography in both two and three dimensions. The Young's moduli of the scaffolds under conditions of temperature, pH and ionic strength similar to those found in the body were tested and were found to be highly dependent on the architectures.

[1]  Yasuhiko Hayashi,et al.  Possible Participation of Autocrine and Paracrine Vascular Endothelial Growth Factors in Hypoxia-induced Proliferation of Endothelial Cells and Pericytes (*) , 1995, The Journal of Biological Chemistry.

[2]  J. Davies,et al.  In vitro degradation of a novel poly(lactide-co-glycolide) 75/25 foam. , 1999, Biomaterials.

[3]  D. Sweet Registry of toxic effects of chemical substances , 1987 .

[4]  R. L. Tatken,et al.  Registry of Toxic Effects of Chemical Substances , 1986 .

[5]  Fergal J O'Brien,et al.  Influence of freezing rate on pore structure in freeze-dried collagen-GAG scaffolds. , 2004, Biomaterials.

[6]  M. Davidson,et al.  Architecture control of three-dimensional polymeric scaffolds for soft tissue engineering. I. Establishment and validation of numerical models. , 2004, Journal of biomedical materials research. Part A.

[7]  P. Ma,et al.  Microtubular architecture of biodegradable polymer scaffolds. , 2001, Journal of biomedical materials research.

[8]  K. Leong,et al.  Poly(L-lactic acid) foams with cell seeding and controlled-release capacity. , 1996, Journal of biomedical materials research.

[9]  D. Grainger,et al.  Fabrication of poly(α‐hydroxy acid) foam scaffolds using multiple solvent systems , 2002 .

[10]  J. Mazumdar,et al.  Principles of solidification and materials processing , 1990 .

[11]  Henry E. Bass,et al.  Handbook of Elastic Properties of Solids, Liquids, and Gases , 2004 .

[12]  Jeffrey A. Hubbell,et al.  Biomaterials in Tissue Engineering , 1995, Bio/Technology.

[13]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part I. Traditional factors. , 2001, Tissue engineering.

[14]  Y. Ikada,et al.  In vitro and in vivo comparison of bulk and surface hydrolysis in absorbable polymer scaffolds for tissue engineering. , 1999, Journal of biomedical materials research.

[15]  D. Ingber,et al.  Prevascularization of porous biodegradable polymers , 1993, Biotechnology and bioengineering.

[16]  Yang-Jo Seol,et al.  Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[17]  Y. Ikada,et al.  Properties and morphology of poly(L-lactide). III. Effects of initial crystallinity on long-termin vitro hydrolysis of high molecular weight poly(L-lactide) film in phosphate-buffered solution , 2000 .

[18]  K. Char,et al.  The effects of diluent molecular weight on the structure of thermally-induced phase separation membrane , 1995 .

[19]  T. Park,et al.  Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation. , 1999, Journal of biomedical materials research.

[20]  Arnold T. Hagler,et al.  Ab Initio Calculations on Small Molecule Analogs of Polycarbonates , 1995 .

[21]  Dietmar W. Hutmacher,et al.  Scaffold design and fabrication technologies for engineering tissues — state of the art and future perspectives , 2001, Journal of biomaterials science. Polymer edition.

[22]  P. Ma,et al.  Porous poly(L-lactic acid)/apatite composites created by biomimetic process. , 1999, Journal of biomedical materials research.

[23]  P. Moghe,et al.  Substrate microtopography can enhance cell adhesive and migratory responsiveness to matrix ligand density. , 2001, Journal of biomedical materials research.

[24]  S. Blacher,et al.  Preparation of macroporous biodegradable poly(L-lactide-co-epsilon-caprolactone) foams and characterization by mercury intrusion porosimetry, image analysis, and impedance spectroscopy. , 2003, Journal of biomedical materials research. Part A.

[25]  Christian Grandfils,et al.  Biodegradable and macroporous polylactide implants for cell transplantation: 1. Preparation of macroporous polylactide supports by solid-liquid phase separation , 1996 .

[26]  C. M. Agrawal,et al.  Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. , 2001, Journal of biomedical materials research.

[27]  D. R. Lloyd,et al.  Microporous membrane formation via thermally induced phase separation. I. Solid-liquid phase separation , 1990 .

[28]  G. S. Parks,et al.  Thermal Data on Organic Compounds. XIV. Some Heat Capacity, Entropy and Free Energy Data for Cyclic Substances , 1934 .

[29]  T. Park,et al.  Biodegradable polymeric microcellular foams by modified thermally induced phase separation method. , 1999, Biomaterials.