A poly(lactide-co-glycolide)/hydroxyapatite composite scaffold with enhanced osteoconductivity.

Biodegradable polymer/ceramic scaffolds can overcome the limitations of conventional ceramic bone substitutes. However, the conventional methods of polymer/ceramic scaffold fabrication often use organic solvents, which might be harmful to cells or tissues. Moreover, scaffolds fabricated with the conventional methods have limited ceramic exposure on the scaffold surface since the polymer solution envelopes the ceramic particles during the fabrication process. In this study, we developed a novel fabrication method for the efficient exposure of ceramic onto the scaffold surface, which would enhance the osteoconductivity and wettability of the scaffold. Poly(D,L-lactide-co-glycolide)/nanohydroxyapatite (PLGA/HA) scaffolds were fabricated by the gas foaming and particulate leaching (GF/PL) method without the use of organic solvents. Selective staining of ceramic particles indicated that HA nanoparticles exposed to the scaffold surface were observed more abundantly in the GF/PL scaffold than in the conventional solvent casting and particulate leaching (SC/PL) scaffold. Both types of scaffolds were implanted to critical size defects in rat skulls for 8 weeks. The GF/PL scaffolds exhibited significantly enhanced bone regeneration when compared with the SC/PL scaffolds. Histological analyses and microcomputed tomography of the regenerated tissues showed that bone formation was more extensive on the GF/PL scaffolds than on the SC/PL scaffolds. Compared with the SC/PL scaffolds, the enhanced bone formation on the GF/PL scaffolds may result from the higher exposure of HA nanoparticles to the scaffold surface. These results show that the biodegradable polymer/ceramic composite scaffolds fabricated with the novel GF/PL method can enhance bone regeneration compared with those fabricated with the conventional SC/PL method.

[1]  Cato T Laurencin,et al.  Three-dimensional, bioactive, biodegradable, polymer-bioactive glass composite scaffolds with improved mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro. , 2003, Journal of biomedical materials research. Part A.

[2]  A. Aplin,et al.  Anchorage-dependent ERK signaling--mechanisms and consequences. , 2002, Current opinion in genetics & development.

[3]  M. Bonfiglio,et al.  Immunological responses to bone. , 1972 .

[4]  A. Bigi,et al.  Bonelike apatite growth on hydroxyapatite-gelatin sponges from simulated body fluid. , 2002, Journal of biomedical materials research.

[5]  A. Mikos,et al.  Marrow stromal osteoblast function on a poly(propylene fumarate)/beta-tricalcium phosphate biodegradable orthopaedic composite. , 2000, Biomaterials.

[6]  K. Burg,et al.  Biomaterial developments for bone tissue engineering. , 2000, Biomaterials.

[7]  Young Ha Kim,et al.  Smooth muscle-like tissues engineered with bone marrow stromal cells. , 2004, Biomaterials.

[8]  H. D. Boer THE HISTORY OF BONE GRAFTS , 1988 .

[9]  H. Aoki,et al.  Mechanical properties of sintered hydroxyapatite for prosthetic applications , 1981 .

[10]  Cato T Laurencin,et al.  Novel polymer-synthesized ceramic composite-based system for bone repair: an in vitro evaluation. , 2004, Journal of biomedical materials research. Part A.

[11]  K. Anselme,et al.  Osteoblast adhesion on biomaterials. , 2000, Biomaterials.

[12]  S. Stupp,et al.  Organoapatites: materials for artificial bone. I. Synthesis and microstructure. , 1992, Journal of biomedical materials research.

[13]  A. Coombes,et al.  Resorbable synthetic polymers as replacements for bone graft. , 1994, Clinical materials.

[14]  L. Guan,et al.  Preparation and characterization of a highly macroporous biodegradable composite tissue engineering scaffold. , 2004, Journal of biomedical materials research. Part A.

[15]  P. Ma,et al.  Poly(alpha-hydroxyl acids)/hydroxyapatite porous composites for bone-tissue engineering. I. Preparation and morphology. , 1999, Journal of biomedical materials research.

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

[17]  Peter X Ma,et al.  Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. , 2004, Biomaterials.

[18]  D. Wise,et al.  Enhanced bioactivity of a poly(propylene fumarate) bone graft substitute by augmentation with nano-hydroxyapatite. , 2003, Bio-medical materials and engineering.

[19]  F. Delannay,et al.  The influence of high sintering temperatures on the mechanical properties of hydroxylapatite , 1995 .

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

[21]  M. Textor,et al.  Biodegradable polymer/hydroxyapatite composites: surface analysis and initial attachment of human osteoblasts. , 2001, Journal of biomedical materials research.

[22]  Seung‐Woo Cho,et al.  Engineering of volume-stable adipose tissues. , 2005, Biomaterials.

[23]  Min Wang,et al.  Developing bioactive composite materials for tissue replacement. , 2003, Biomaterials.

[24]  J. Vacanti,et al.  Tissue-engineered growth of bone and cartilage. , 1993, Transplantation proceedings.

[25]  Jiang Chang,et al.  Preparation and characterization of bioactive and biodegradable Wollastonite/poly(D,L-lactic acid) composite scaffolds , 2004, Journal of materials science. Materials in medicine.

[26]  Byung-Soo Kim,et al.  A poly(lactic acid)/calcium metaphosphate composite for bone tissue engineering. , 2005, Biomaterials.

[27]  R. Reis,et al.  Bionert and biodegradable polymeric matrix composites filled with bioactive SiO2−3CaO·P2O5−MgO glasses and glass-ceramics , 1997 .

[28]  Jennifer M. Vandiver,et al.  Nanoscale variation in surface charge of synthetic hydroxyapatite detected by chemically and spatially specific high-resolution force spectroscopy. , 2005, Biomaterials.

[29]  J. Planell,et al.  Effect of the particle size on the micro and nanostructural features of a calcium phosphate cement: a kinetic analysis. , 2004, Biomaterials.

[30]  Byung-Soo Kim,et al.  Thermally produced biodegradable scaffolds for cartilage tissue engineering. , 2004, Macromolecular bioscience.

[31]  Y. Koyama,et al.  In Vitro and In Vivo Tests of Newly Developed TCP/CPLA Composites , 1997 .

[32]  R. Martinetti,et al.  Resorption of composite polymer-hydroxyapatite membranes: a time-course study in rabbit. , 1997, Biomaterials.

[33]  Young Ha Kim,et al.  Tissue Engineering of Smooth Muscle under a Mechanically Dynamic Condition , 2003 .

[34]  Lichun Lu,et al.  Synthetic bone substitutes , 2000 .