Functionalization of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering.
Scaffolds exhibiting biological recognition and specificity play an important role in tissue engineering and regenerative medicine. The bioactivity of scaffolds in turn influences, directs, or manipulates cellular responses. In this study, chitosan/poly(lactic acid-co-glycolic acid) (chitosan/PLAGA) sintered microsphere scaffolds were functionalized via heparin immobilization. Heparin was successfully immobilized on chitosan/PLAGA scaffolds with controllable loading efficiency. Mechanical testing showed that heparinization of chitosan/PLAGA scaffolds did not significantly alter the mechanical properties and porous structures. In addition, the heparinized chitosan/PLAGA scaffolds possessed a compressive modulus of 403.98 +/- 19.53 MPa and a compressive strength of 9.83 +/- 0.94 MPa, which are in the range of human trabecular bone. Furthermore, the heparinized chitosan/PLAGA scaffolds had an interconnected porous structure with a total pore volume of 30.93 +/- 0.90% and a median pore size of 172.33 +/- 5.89 mum. The effect of immobilized heparin on osteoblast-like MC3T3-E1 cell growth was investigated. MC3T3-E1 cells proliferated three dimensionally throughout the porous structure of the scaffolds. Heparinized chitosan/PLAGA scaffolds with low heparin loading (1.7 microg/scaffold) were shown to be capable of stimulating MC3T3-E1 cell proliferation by MTS assay and cell differentiation as evidenced by elevated osteocalcin expression when compared with nonheparinized chitosan/PLAGA scaffold and chitosan/PLAGA scaffold with high heparin loading (14.1 microg/scaffold). This study demonstrated the potential of functionalizing chitosan/PLAGA scaffolds via heparinization with improved cell functions for bone tissue engineering applications.
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904, USA.
Tao
T
Jiang
Yusuf
Y
Khan
Lakshmi S
LS
Nair
Wafa I
WI
Abdel-Fattah
Cato T
CT
Laurencin
D000327:Adsorption / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D019245:Compressive Strength / Q000187:drug effects; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D055767:Immobilized Proteins / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015675:Osteocalcin / Q000378:metabolism; D056951:Photoelectron Spectroscopy; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D013499:Surface Properties / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
D055767:Immobilized Proteins; D015675:Osteocalcin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006493:Heparin; D048271:Chitosan; D000469:Alkaline Phosphatase