Control of pore size and structure of tissue engineering scaffolds produced by supercritical fluid processing.

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 under investigation were temperature (from 5 to 55 degrees C) and pressure (from 60 to 230 bar). A series of amorphous PDLLA and PLGA polymers with various molecular weights (from 13 KD to 96 KD) and/or chemical compositions (the mole percentage of glycolic acid in the polymers was 0, 15, 25, 35 and 50 respectively) were employed. The resulting scaffolds were characterised by optical microscopy, scanning electron microscopy (SEM), and micro X-ray computed tomography (microCT). This is the first detailed study on using these series polymers for scaffold formation by supercritical technique. This study has demonstrated that the pore size and structure of the supercritical PDLLA and PLGA scaffolds can be tailored by careful control of processing conditions.

[1]  C. Tanford Macromolecules , 1994, Nature.

[2]  E. Beckman,et al.  Generation of microcellular polymeric foams using supercritical carbon dioxide. II: Cell growth and skin formation , 1994 .

[3]  C. Eckert,et al.  Infrared cell for supercritical fluid–polymer interactions , 1996 .

[4]  W. D. Spall,et al.  Interaction of supercritical carbon dioxide with polymers. II. Amorphous polymers , 1996 .

[5]  R Langer,et al.  Novel approach to fabricate porous sponges of poly(D,L-lactic-co-glycolic acid) without the use of organic solvents. , 1996, Biomaterials.

[6]  W. D. Spall,et al.  Interaction of supercritical carbon dioxide with polymers. I: Crystalline polymers , 1996 .

[7]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[8]  T. J. McCarthy,et al.  Preparation and Characterization of Microcellular Polystyrene Foams Processed in Supercritical Carbon Dioxide , 1998 .

[9]  D J Mooney,et al.  Open pore biodegradable matrices formed with gas foaming. , 1998, Journal of biomedical materials research.

[10]  C. Stafford,et al.  Expansion of Polystyrene Using Supercritical Carbon Dioxide: Effects of Molecular Weight, Polydispersity, and Low Molecular Weight Components , 1999 .

[11]  J. R. Royer,et al.  Carbon Dioxide-Induced Swelling of Poly(dimethylsiloxane) , 1999 .

[12]  R Langer,et al.  In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid) foams. , 2000, Biomaterials.

[13]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[14]  D J Mooney,et al.  Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[15]  D H Kohn,et al.  Sustained release of vascular endothelial growth factor from mineralized poly(lactide-co-glycolide) scaffolds for tissue engineering. , 2000, Biomaterials.

[16]  A. Akgerman,et al.  Active growth factor delivery from poly(D,L-lactide-co-glycolide) foams prepared in supercritical CO(2). , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[17]  T. Park,et al.  A novel fabrication method of macroporous biodegradable polymer scaffolds using gas foaming salt as a porogen additive. , 2000, Journal of biomedical materials research.

[18]  Martyn C. Davies,et al.  Supercritical fluid mixing: preparation of thermally sensitive polymer composites containing bioactive materials , 2001 .

[19]  A. Cooper Recent Developments in Materials Synthesis and Processing Using Supercritical CO2 , 2001 .

[20]  Xuebin B. Yang,et al.  Adenoviral BMP-2 gene transfer in mesenchymal stem cells: in vitro and in vivo bone formation on biodegradable polymer scaffolds. , 2002, Biochemical and biophysical research communications.

[21]  K. Shakesheff,et al.  Incorporation of Proteins into Polymer Materials by a Novel Supercritical Fluid Processing Method , 2002 .

[22]  David J Mooney,et al.  Salt fusion: an approach to improve pore interconnectivity within tissue engineering scaffolds. , 2002, Tissue engineering.

[23]  Daniel Howard,et al.  Immunoselection and adenoviral genetic modulation of human osteoprogenitors: in vivo bone formation on PLA scaffold. , 2002, Biochemical and biophysical research communications.

[24]  Xiangmin Han,et al.  A Review of CO2 Applications in the Processing of Polymers , 2003 .

[25]  Jae-Hyung Jang,et al.  Controllable delivery of non-viral DNA from porous scaffolds. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[26]  Jan Feijen,et al.  Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique. , 2003, Biomaterials.

[27]  M. Pishko,et al.  Solvent-Free Protein Encapsulation within Biodegradable Polymer Foams , 2004, Drug delivery.

[28]  David J Mooney,et al.  Role of poly(lactide-co-glycolide) particle size on gas-foamed scaffolds , 2004, Journal of biomaterials science. Polymer edition.

[29]  J. Lannutti,et al.  Bioactive polymer surfaces via supercritical fluids , 2004 .

[30]  Buddy D Ratner,et al.  Generation of porous microcellular 85/15 poly (DL-lactide-co-glycolide) foams for biomedical applications. , 2004, Biomaterials.

[31]  Kevin M. Shakesheff,et al.  Supercritical fluid technologies and tissue engineering scaffolds , 2004 .

[32]  Xuebin B. Yang,et al.  Human osteoprogenitor bone formation using encapsulated bone morphogenetic protein 2 in porous polymer scaffolds. , 2004, Tissue engineering.

[33]  S. Howdle,et al.  Porous methacrylate scaffolds: supercritical fluid fabrication and in vitro chondrocyte responses. , 2004, Biomaterials.

[34]  K. Shakesheff,et al.  Materials processing in supercritical carbon dioxide: surfactants, polymers and biomaterials , 2004 .

[35]  K. Shakesheff,et al.  Supercritical carbon dioxide: putting the fizz into biomaterials , 2005, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[36]  I. Marrucho,et al.  Carbon dioxide, ethylene and water vapor sorption in poly(lactic acid) , 2006 .

[37]  T. Park,et al.  Gas foamed open porous biodegradable polymeric microspheres. , 2006, Biomaterials.

[38]  The effect of an admix of bone morphogenetic proteins on human osteoprogenitor activity in vitro and in vivo , 2006 .

[39]  I. Marrucho,et al.  Gas solubility of carbon dioxide in poly(lactic acid) at high pressures , 2006 .

[40]  L. Janssen,et al.  The FT-IR studies of the interactions of CO2 and polymers having different chain groups , 2006 .

[41]  S. Sosnowski,et al.  Polyester scaffolds with bimodal pore size distribution for tissue engineering. , 2006, Macromolecular bioscience.

[42]  K. Shakesheff,et al.  Development of a slow non‐viral DNA release system from PDLLA scaffolds fabricated using a supercritical CO2 technique , 2007, Biotechnology and bioengineering.

[43]  D. Tomasko,et al.  Carbon dioxide sorption and dilation of poly(lactide-co-glycolide) , 2007 .