Repair of diaphyseal bone defects with calcitriol-loaded PLGA scaffolds and marrow stromal cells.
Calcitriol (1,25(OH)2D3)-loaded porous poly(D,L-lactide-co-glycolide) (PLGA) scaffolds prepared by solvent casting/salt leaching method were used to repair a 1.5 cm diaphyseal segmental bone defect as a fully absorbable osteogenic biomaterial. The in vitro release of sulforhodamine B (SRB) from PLGA scaffold was measured using spectrophotometer, considering SRB as a model drug. The SRB released from SRB-incorporated PLGA scaffold during 3 months was with relatively low initial burst. The calcitriol-loaded PLGA scaffolds with or without marrow stromal cells (MSCs) were implanted in a critical-sized intercalated bone defect in rabbit femur. Defects were assessed by radiographs until 9 weeks. The bony union of the defect was observed only in the calcitriol-loaded groups. RT-PCR results indicated that MSCs, which were seeded into calcitriol-loaded scaffold, expressed an increased level of alkaline phosphatase, osteonectin, and type I collagen mRNA at day 10. After 2 and 4 weeks, the implanted scaffolds were evaluated by histology. New osteoid matrix and direct calcium deposits were more evident in calcitriol/PLGA/MSC group. Three-dimensional computed tomography and frontal tomographic images of repaired femur showed that normal femur anatomy had been restored with cortical bone with no implanted PLGA remnants at 20 weeks. It can be concluded that the porous calcitriol-loaded PLGA scaffold combined with MSCs may be a novel method for repairing the large loaded bone defect.
Yoon
Sun Jung
SJ
BK-21 Polymer Fusion Research Team, Chonbuk National University, Jeonju, Republic of Korea.
Park
Ki Suk
KS
Kim
Moon Suk
MS
Rhee
John M
JM
Khang
Gilson
G
Lee
Hai Bang
HB
D020341:Absorbable Implants; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology*; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000627:therapeutic use; D002113:Calcification, Physiologic; D002117:Calcitriol; D003692:Delayed-Action Preparations; D018483:Diaphyses / Q000293:injuries; D004343:Drug Implants / Q000627:therapeutic use; D005269:Femur / Q000000981:diagnostic imaging / Q000293:injuries* / Q000378:metabolism; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D017154:Stromal Cells / Q000166:cytology; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D000943:Antigens, Differentiation; D018786:Bone Substitutes; D003692:Delayed-Action Preparations; D004343:Drug Implants; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002117:Calcitriol