title: In vivo bioactivity of rhBMP-2 delivered with novel polyelectrolyte complexation shells assembled on an alginate microbead core template.
abstract: Electrostatic interactions between polycations and polyanions are being explored to fabricate polyelectrolyte complexes (PEC) that could entrap and regulate the release of a wide range of biomolecules. Here, we report the in vivo application of PEC shells fabricated from three different polycations: poly-l-ornithine (PLO), poly-l-arginine (PLA) and DEAE-dextran (DEAE-D) to condense heparin on the surface of alginate microbeads and further control the delivery of recombinant human bone morphogenetic protein 2 (rhBMP-2) in spinal fusion application. We observed large differences in the behavior of PEC shells fabricated from the cationic polyamino acids (PLO and PLA) when compared to the cationic polysaccharide, DEAE-D. Whereas DEAE-D-based PEC shells eroded and released rhBMP-2 over 2 days in vitro, PLO- and PLA-based shells retained at least 60% of loaded rhBMP-2 after 3 weeks of incubation in phosphate-buffered saline. In vivo implantation in a rat model of posterolateral spinal fusion revealed robust bone formation in the PLO- and PLA-based PEC shell groups. This resulted in a significantly enhanced mechanical stability of the fused segments. However, bone induction and biomechanical stability of spine segments implanted with DEAE-D-based carriers were significantly inferior to both PLO- and PLA-based PEC shell groups (p<0.01). From these results, we conclude that PEC shells incorporating native heparin could be used for growth factor delivery in functional bone tissue engineering application and that PLA- and PLO-based complexes could represent superior options to DEAE-D for loading and in vivo delivery of bioactive BMP-2 in this approach.
authors: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Sunny-Akogwu
authors: SA
authors: Abbah
authors: Jing
authors: J
authors: Liu
authors: Raymond W M
authors: RW
authors: Lam
authors: James C H
authors: JC
authors: Goh
authors: Hee-Kit
authors: HK
authors: Wong
mesh_terms: D000464:Alginates / Q000737:chemistry; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003637:DEAE-Dextran / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006493:Heparin / Q000008:administration & dosage* / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008297:Male; D051379:Mice; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D013131:Spine; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D006603:Hexuronic Acids; D010455:Peptides; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C008973:polyornithine; C015462:polyarginine; D020723:Glucuronic Acid; D006493:Heparin; D003637:DEAE-Dextran; D000469:Alkaline Phosphatase