Insulin-like growth factor I-releasing alginate-tricalciumphosphate composites for bone regeneration.
OBJECTIVE
Development and characterization of an in situ-forming, osteoconductive, and growth factor-releasing bone implant.


METHODS
Injectable in situ-forming scaffolds were prepared from a 2% (m/v) alginate solution, tricalciumphosphate (TCP) granules, and poly(lactide-co-glycolide) microspheres (MS), loaded with the osteoinductive growth factor insulin-like growth factor I (IGF-I). Scaffolds were prepared by mixing the components followed by hydrogel formation through calcium carbonate-induced physical cross-linking of the alginate at slightly acidic pH. Physical-chemical properties and cell biocompatibility using osteoblast-like cells (MG-63 and Saos-2) of these scaffolds were investigated.


RESULTS
The addition of TCP to the alginate resulted in reduced swelling and gelation time and an increase in stiffness. Osteoblast-like cells (MG-63 and Saos-2) did not show toxic reactions and adhered circumferentially to the TCP granules surface. The addition of the IGF-I MS resulted in an up to sevenfold increased proliferation rate of MG-63 cells as compared to scaffold preparations without IGF-I MS. The alkaline phosphate (ALP) activity-a parameter for osteblastic activity-increased with increasing amounts of TCP in Saos-2 loaded composite scaffolds.


CONCLUSIONS
A prototype in situ-hardening composite system for conformal filling of bone defects supporting osteoblastic activity for further clinical testing in relevant fracture models was developed and characterized.
Luginbuehl
Vera
V
Institute of Pharmaceutical Sciences, Drug Formulation and Delivery Group, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland.
Wenk
Esther
E
Koch
Annette
A
Gander
Bruno
B
Merkle
Hans P
HP
Meinel
Lorenz
L
D000464:Alginates; D000465:Algorithms; D000469:Alkaline Phosphatase / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D003692:Delayed-Action Preparations; D006801:Humans; D020100:Hydrogels; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D012212:Rheology; D013314:Stress, Mechanical
D000464:Alginates; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D020100:Hydrogels; D007334:Insulin-Like Growth Factor I; D004247:DNA; D000469:Alkaline Phosphatase; C018392:tricalcium phosphate