Local controlled release of VEGF and PDGF from a combined brushite-chitosan system enhances bone regeneration.
The two growth factors VEGF and PDGF are involved in the process of bone regeneration. For this reason, we developed a brushite-chitosan system which controls the release kinetics of incorporated VEGF and PDGF to enhance bone healing. PDGF (250 ng) was incorporated in the liquid phase. Alginate microsphere-encapsulated VEGF (350 ng) was pre-included in small cylindrical chitosan sponges. VEGF and PDGF release kinetics and tissue distribution were determined using iodinated ((125)I) growth factor. In vivo, PDGF was more rapidly delivered from these systems implanted in rabbit femurs than VEGF. 80% of PDGF was released by the end of two weeks while only 70% of VEGF was delivered after a period of three weeks. Both GFs released from the brushite-chitosan constructs remained located around the implantation site (5 cm) with negligible systemic exposure. A PDGF bone peak concentration of approximately 5 ng/g was achieved on the 4th day. Thereafter, PDGF concentrations stayed higher than 2 ng/g during the first week. These scaffolds also provided a local VEGF bone concentration above 3 ng/g during a total of 4weeks, with a peak concentration of 5.5 ng/g on the 7th day. The present work demonstrates that our brushite-chitosan system is capable of controlling the release rate and localization of both GFs within a bone defect. The effect on bone formation was considerably enhanced with PDGF loaded brushite-chitosan scaffolds as well as with the PDGF/VEGF combination.
De la Riva
Beatriz
B
Department of Chemical Engineering and Pharmaceutical Technology, University of La Laguna, 38200 La Laguna, Spain.
Sánchez
Esther
E
Hernández
Antonio
A
Reyes
Ricardo
R
Tamimi
Faleh
F
López-Cabarcos
Enrique
E
Delgado
Araceli
A
Evora
Carmen
C
D000464:Alginates / Q000737:chemistry; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D005269:Femur / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016062:Porosity; D011817:Rabbits; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D000464:Alginates; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006603:Hexuronic Acids; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D020723:Glucuronic Acid; D048271:Chitosan; C494366:calcium phosphate, dibasic, dihydrate