Bone tissue engineering in a rotating bioreactor using a microcarrier matrix system.
A novel approach was utilized to grow in vitro mineralized bone tissue using lighter-than-water, polymeric scaffolds in a high aspect ratio rotating bioreactor. We have adapted polymer microencapsulation methods for the formation of hollow, lighter-than-water microcarriers of degradable poly(lactic-co-glycolic acid). Scaffolds were fabricated by sintering together lighter-than-water microcarriers from 500 to 860 microm in diameter to create a fully interconnected, three-dimensional network with an average pore size of 187 microm and aggregate density of 0.65 g/mL. Motion in the rotating bioreactor was characterized by numerical simulation and by direct measurement using an in situ particle tracking system. Scaffold constructs established a near circular trajectory in the fluid medium with a terminal velocity of 98 mm/s while avoiding collision with the bioreactor wall. Preliminary cell culture studies on these scaffolds show that osteoblast-like cells readily attached to microcarrier scaffolds using controlled seeding conditions with an average cell density of 6.5 x 10(4) cells/cm(2). The maximum shear stress imparted to attached cells was estimated to be 3.9 dynes/cm(2). In addition, cells cultured in vitro on these lighter-than-water scaffolds retained their osteoblastic phenotype and showed significant increases in alkaline phosphatase expression and alizarin red staining by day 7 as compared with statically cultured controls.
Center for Advanced Biomaterials and Tissue Engineering, Department of Chemical Engineering, Drexel University, Philadelphia, Pennsylvania 19104, USA.
E A
EA
Botchwey
S R
SR
Pollack
E M
EM
Levine
C T
CT
Laurencin
D000469:Alkaline Phosphatase / Q000378:metabolism; D001672:Biocompatible Materials; D001698:Biomedical Engineering / Q000379:methods*; D019149:Bioreactors; D016025:Bone Transplantation; D002214:Capsules; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D019344:Lactic Acid; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology; D010012:Osteogenesis; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D014182:Transplantation, Autologous
D001672:Biocompatible Materials; D002214:Capsules; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase