Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers.
Cartilaginous implants for potential use in reconstructive or orthopedic surgery were created using chondrocytes grown on synthetic, biodegradable polymer scaffolds. Chondrocytes isolated from bovine or human articular or costal cartilage were cultured on fibrous polyglycolic acid (PGA) and porous poly(L)lactic acid (PLLA) and used in parallel in vitro and in vivo studies. Samples were taken at timed intervals for assessment of cell number and cartilage matrix (sulfated glycosaminoglycan [S-GAG], collagen). The chondrocytes secreted cartilage matrix to fill the void spaces in the polymer scaffolds that were simultaneously biodegrading. In vitro, chondrocytes grown on PGA for 6 weeks reached a cell density of 5.2 x 10(7) cells/g, which was 8.3-fold higher than at day 1, and equalled the cellularity of normal bovine articular cartilage. In vitro, the cell growth rate was approximately twice as high on PGA as it was on PLLA; cells grown on PGA produced S-GAG at a high steady rate, while cells grown on PLLA produced only minimal amounts of S-GAG. These differences could be attributed to polymer geometry and biodegradation rate. In vivo, chondrocytes grown on both PGA and PLLA for 1-6 months maintained the three-dimensional (3-D) shapes of the original polymer scaffolds, appeared glistening white macroscopically, contained S-GAG and type II collagen, and closely resembled cartilage histologically. These studies demonstrate the feasibility of culturing isolated chondrocytes on biodegradable polymer scaffolds to regenerate 3-D neocartilage.
Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
L E
LE
Freed
J C
JC
Marquis
A
A
Nohria
J
J
Emmanual
A G
AG
Mikos
R
R
Langer
D000818:Animals; D001673:Biodegradation, Environmental; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D002417:Cattle; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005240:Feasibility Studies; D006801:Humans; D007773:Lactates; D019344:Lactic Acid; D051379:Mice; D008819:Mice, Nude; D011091:Polyesters; D011100:Polyglycolic Acid; D011108:Polymers; D019736:Prostheses and Implants; D012272:Ribs / Q000166:cytology; D013997:Time Factors; D014183:Transplantation, Heterologous
D007773:Lactates; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)