Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.
OBJECTIVE
Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery.


METHODS
EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation.


RESULTS
At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th).


CONCLUSIONS
The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors.
Department of Biomedical Engineering, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan. Electronic address: harry-2001@yahoo.com.tw.
N-J
NJ
Chang
C-F
CF
Lam
C-C
CC
Lin
W-L
WL
Chen
C-F
CF
Li
Y-T
YT
Lin
M-L
ML
Yeh
D000818:Animals; D001672:Biocompatible Materials; D001861:Bone Regeneration / Q000502:physiology; D002358:Cartilage, Articular / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology; D042783:Endothelial Cells / Q000637:transplantation*; D005269:Femur / Q000098:blood supply / Q000473:pathology / Q000502:physiology; D019344:Lactic Acid; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D055114:X-Ray Microtomography / Q000379:methods
D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
Animal model; Cartilage tissue engineering; Endothelial progenitor cells; Extracellular matrix; Regenerative medicine; Scaffold