The effect of mesenchymal populations and vascular endothelial growth factor delivered from biodegradable polymer scaffolds on bone formation.
The capacity to deliver, temporally, bioactive growth factors in combination with appropriate progenitor and stem cells to sites of tissue regeneration promoting angiogenesis and osteogenesis offers therapeutic opportunities in regenerative medicine. We have examined the bone regenerative potential of encapsulated vascular endothelial growth factor (VEGF(165)) biodegradable poly(DL-lactic acid) (PLA) scaffolds created using supercritical CO(2) fluid technology to encapsulate and release solvent-sensitive and thermolabile growth factors in combination with human bone marrow stromal cells (HBMSC) implanted in a mouse femur segmental defect (5 mm) for 4 weeks. HBMSC seeded on VEGF encapsulated PLA scaffolds showed significant bone regeneration in the femur segmental defect compared to the scaffold alone and scaffold seeded with HBMSC as analysed by indices of increased bone volume (BV mm(3)), trabecular number (Tb.N/mm) and reduced trabecular separation (Tb.Sp.mm) in the defect region using micro-computed tomography. Histological examination confirmed significant new bone matrix in the HBMSC seeded VEGF encapsulated scaffold group as evidenced by Sirius red/alcian blue and Goldner's trichrome staining and type I collagen immunocytochemistry expression in comparison to the other groups. These studies demonstrate the ability to deliver, temporally, a combination of VEGF released from scaffolds with seeded HBMSC to sites of bone defects, results in enhanced regeneration of a bone defect.
Kanczler
Janos M
JM
Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Developmental Origins of Health and Disease, Institute of Developmental Sciences, University of Southampton, Southampton, UK.
Ginty
Patrick J
PJ
Barry
John J A
JJ
Clarke
Nicholas M P
NM
Howdle
Steve M
SM
Shakesheff
Kevin M
KM
Oreffo
Richard O C
RO
D020341:Absorbable Implants; D000818:Animals; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004337:Drug Carriers / Q000737:chemistry; D005264:Femoral Fractures / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis / Q000187:drug effects*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry
D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019344:Lactic Acid; C033616:poly(lactide)