In vivo bioactivity of rhBMP-2 delivered with novel polyelectrolyte complexation shells assembled on an alginate microbead core template

Abbah, Sunny Akogwu; Liu, Jing; Lam, Raymond W.; Goh, James Cho‐Hong; Wong, Hee‐Kit

doi:10.1016/j.jconrel.2012.07.027

Cited by 47 publications

(47 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…the osteogenic effects is complex, mainly owing to the reversible, noncovalent interactions between heparin and heparin-binding GFs, which ensure minimal impact on GF structure. 13,30,37,39,43,44,[48][49][50][51][52] We demonstrated that the nanocomplexes in our study not only effectively loaded and sustained release of PlGF-2/BMP-2, but also maintained their bioactivities for bone regeneration. A key result in this study was the bioactivity of the released PlGF-2 being comparable to that of the released BMP-2, despite its dose being half that of BMP-2.…”

supporting

confidence: 52%

“…45 Accordingly, the sequential release kinetics indicated in this study may apply: in brief, the nanocomplexes release more PlGF-2 in the early phase to enhance angiogenesis; then, the subsequently released PlGF-2, at this point at lower concentrations than BMP-2, enhances direct osteogenesis in coordination with BMP-2. In this study, heparin acts as a "sandwich" or "double duty" component and interacts with HTCC to form highly stable polyelectrolyte complexes 37 that have been demonstrated to effectively load GFs and maintain their bioactivities. 13,30,44,46 The minimal initial release may be attributed to the release of GFs that were physically adsorbed onto the heparin-HCCT nanocomplexes.…”

Section: Sustained Release Of Plgf-2/bmp-2mentioning

confidence: 99%

See 1 more Smart Citation

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Liu

Deng

Sun

et al. 2016

IJN

View full text Add to dashboard Cite

Objective To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). Methods Three groups of PlGF-2/BMP-2-loaded heparin– N -(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 μg PlGF-2; with 1.0 μg BMP-2; and with 0.5 μg PlGF-2 combined with 1.0 μg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. Results The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%–84% of PlGF-2 and 89%–91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. Conclusion PlGF-2-loaded heparin–HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone.

show abstract

supporting

confidence: 52%

Section: Sustained Release Of Plgf-2/bmp-2mentioning

confidence: 99%

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Liu

Deng

Sun

et al. 2016

IJN

View full text Add to dashboard Cite

show abstract

“…It finds applications in tissue engineering for skin 3 , nerve 4 , bone 5 , and cartilage regeneration 6 , and in drug delivery systems 7 . Depending on the different uses, a variety of sodium alginate (SA) structures, such as films 8 , particles 9 , sponges 10 , or fibres 11 , have been proposed.…”

Section: Introductionmentioning

confidence: 99%

Alginate Nanofibrous Mats with Adjustable Degradation Rate for Regenerative Medicine

et al. 2015

View full text Add to dashboard Cite

KEYWORDS: alginate, nanofibres, controlled biodegradation ABSTRACT: The broad utilization of electrospun scaffolds of sodium alginate in tissue engineering is strongly limited by their high solubility in aqueous environments and by the difficulty to adjust their degradation dynamics. Here, an alternative strategy to enhance the stability and to control the degradability of alginate nanofibres is described by treating them with trifluoroacetic acid for specific time intervals. It is demonstrated that by increasing the duration of the acid treatment procedure, lower degradation rate of the resulting fibres in buffer solutions can be achieved. Furthermore, the produced mats are free from cytotoxic compounds and highly biocompatible. The properties conferred to the alginate nanofibrous mats by the proposed method are extremely attractive in the production of innovative biomedical devices.2

show abstract

“…The bead-fabrication process and the implant scheme were previously illustrated. 17,18 The outer PEC layer was deposited by sequential incubation in 0.1% poly-l-lysine (PLL; MW = 15,000-30,000) solution followed by washing in water and then incubated in 0.5% sodium heparin solution to form single PEC bilayer deposit. Repeat of this cycle of washing, PLL deposition, washing, and heparin deposition allows subsequent PEC bilayer depositions.…”

Section: Methodsmentioning

confidence: 99%

Sequestration of rhBMP-2 into Self-Assembled Polyelectrolyte Complexes Promotes Anatomic Localization of New Bone in a Porcine Model of Spinal Reconstructive Surgery

Abbah

Lam²,

Hu³

et al. 2014

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

Efficient and therapeutically safe delivery of recombinant human bone morphogenetic protein 2 (rhBMP-2) continues to be a central issue in bone tissue engineering. Recent evidence indicates that layer-by-layer selfassembly of polyelectrolyte complexes (PECs) can be used to recreate synthetic matrix environments that would act as tuneable reservoirs for delicate biomolecules and cells. Although preliminary in vitro as well as small-animal in vivo studies support this premise, translation into clinically relevant bone defect volumes in larger animal models remains unreported. Here we explored the use of native heparin-based PEC, deposited on a hydrated alginate gel template, to load bioactive rhBMP-2 and to facilitate lumbar interbody spinal fusion in pigs. We observed that triple PEC deposits with the highest protein sequestration efficiency and immobilization capacity promoted higher volume of new bone formation when compared with single PEC with low sequestration efficiency and immobilization capacity. This also resulted in a significantly enhanced biomechanical stability of the fused spinal segment when compared with PEC carriers with relatively low protein sequestration and immobilization capacities ( p < 0.05). Most importantly, PEC carriers showed a more orderly pattern of new bone deposition and superior containment of bone tissue within implant site when compared to collagen sponge carriers. We conclude that this growth factor sequestration platform is effective in the healing of clinically relevant bone defect volume and could overcome some of the safety concerns and limitations currently associated with rhBMP-2 therapy such as excessive heterotopic ossification.

show abstract

In vivo bioactivity of rhBMP-2 delivered with novel polyelectrolyte complexation shells assembled on an alginate microbead core template

Cited by 47 publications

References 59 publications

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Alginate Nanofibrous Mats with Adjustable Degradation Rate for Regenerative Medicine

Sequestration of rhBMP-2 into Self-Assembled Polyelectrolyte Complexes Promotes Anatomic Localization of New Bone in a Porcine Model of Spinal Reconstructive Surgery

Contact Info

Product

Resources

About