PMID- 22846985
OWN - NLM
STAT- MEDLINE
DCOM- 20130131
LR  - 20181201
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 162
IP  - 2
DP  - 2012 Sep 10
TI  - In vivo bioactivity of rhBMP-2 delivered with novel polyelectrolyte complexation 
      shells assembled on an alginate microbead core template.
PG  - 364-72
LID - 10.1016/j.jconrel.2012.07.027 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Abbah, Sunny-Akogwu
AU  - Abbah SA
AD  - Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National 
      University of Singapore, Singapore.
FAU - Liu, Jing
AU  - Liu J
FAU - Lam, Raymond W M
AU  - Lam RW
FAU - Goh, James C H
AU  - Goh JC
FAU - Wong, Hee-Kit
AU  - Wong HK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120727
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Alginates)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Drug Carriers)
RN  - 0 (Hexuronic Acids)
RN  - 0 (Peptides)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (recombinant human bone morphogenetic protein-2)
RN  - 25104-12-5 (polyornithine)
RN  - 25212-18-4 (polyarginine)
RN  - 8A5D83Q4RW (Glucuronic Acid)
RN  - 9005-49-6 (Heparin)
RN  - 9015-73-0 (DEAE-Dextran)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alginates/chemistry
MH  - Alkaline Phosphatase/metabolism
MH  - Animals
MH  - Bone Morphogenetic Protein 2/*administration & dosage/chemistry
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - DEAE-Dextran/administration & dosage/chemistry
MH  - Drug Carriers/*administration & dosage/chemistry
MH  - Glucuronic Acid/chemistry
MH  - Heparin/*administration & dosage/chemistry
MH  - Hexuronic Acids/chemistry
MH  - Male
MH  - Mice
MH  - Microspheres
MH  - Osteogenesis/drug effects
MH  - Peptides/administration & dosage/chemistry
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/administration & dosage/chemistry
MH  - Spine
MH  - Transforming Growth Factor beta/*administration & dosage/chemistry
EDAT- 2012/08/01 06:00
MHDA- 2013/02/01 06:00
CRDT- 2012/08/01 06:00
PHST- 2012/04/04 00:00 [received]
PHST- 2012/07/14 00:00 [revised]
PHST- 2012/07/23 00:00 [accepted]
PHST- 2012/08/01 06:00 [entrez]
PHST- 2012/08/01 06:00 [pubmed]
PHST- 2013/02/01 06:00 [medline]
AID - S0168-3659(12)00584-6 [pii]
AID - 10.1016/j.jconrel.2012.07.027 [doi]
PST - ppublish
SO  - J Control Release. 2012 Sep 10;162(2):364-72. doi: 10.1016/j.jconrel.2012.07.027. 
      Epub 2012 Jul 27.