Affinity-selected heparan sulfate for bone repair

Murali, Sadasivam; Rai, Bina; Dombrowski, Christian; Lee, J.L.J.; Lim, Zophia X.H.; Bramono, Diah S.; Lü, Ling; Bell, Tracey; Hinkley, Simon F.R.; Nathan, Soosai; Hui, James; Wong, Hee‐Kit; Nurcombe, Victor; Cool, Simon M.

doi:10.1016/j.biomaterials.2013.04.017

Cited by 72 publications

(95 citation statements)

References 54 publications

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“…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%

“…38,39,43 Also, Martino et al 40 showed that domain II (Fg β15-66 (2) ) of heparin exhibits high affinity for GFs in general, but with heparin displaying a fourfold stronger affinity for PlGF-2 than for BMP-2; 44 they also revealed a specific heparin-binding portion of PlGF-2 spanning residues 123-144 and having the sequence RRPKGRGKRRREKQRPTDCHL. 44 However, in our study, the difference of loading efficiency between PlGF-2 and BMP-2 was not so prominent, perhaps because both GFs were applied at overall low doses and exhibited high affinity to heparin.…”

mentioning

confidence: 99%

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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

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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.

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supporting

confidence: 52%

mentioning

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

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“…This observation suggests that dextran sulfate can play a similar role in the binding of heparin-binding proteins as heparin itself. Similar conclusions have been reported in the literature for this and other heparin-mimics [33,34]. The lack of differences between T1107 and PEGAm is more surprising, but we have to consider that, in general, both molecules are expected to bear one cationic charge under physiological conditions, both are hydrophilic, and both are characterized by long PEG chains.…”

Section: Bmp-7 Release Kinetics From Different Polymer Compositionssupporting

confidence: 87%

New scaffolds encapsulating TGF-β3/BMP-7 combinations driving strong chondrogenic differentiation

Crecente‐Campo

Borrajo

Vidal

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

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“…One representative case is the technology platform introduced to engineer growth factor-binding HS polysaccharides. Instead of conjugating small molecular ligands to the polymer, this approach exploits the natural affinity of the polymer to select and enrich the desired polymers with tailor-made activities against various specific growth factors [17,18]. Another elegant example is to provide multivalent ligands that can organise stem cell receptors into clusters and thereby regulate stem cell differentiation.…”

Section: Opinionmentioning

confidence: 98%

“…When they are large enough -specifically, when the number of their monosaccharide units exceeds 14 -they have considerable binding affinity for vascular endothelial growth factor-165 (VEGF 165 ) [16]. Inspired by this interaction, researchers engineer HS varieties that preferentially bind and enhance various growth factors, including bone morphogenetic protein-2 (BMP-2) [17] and VEGF-A [18], to promote bone healing and blood vessel formation, respectively. Similarly, another polysaccharide, polysialic acid (polySia), forms a large complex (>650 kDa) with fibroblast growth factor 2 (FGF-2) and can enhance FGF-2-mediated cell proliferation when its chain length reaches 17 monosaccharide units [19].…”

mentioning

confidence: 98%