Preparation, structure and BMP-2 controlled release of heparin-conjugated hyaluronan microgels

Zhao, Jianhao; Luo, Chunhong; Chen, Yuqi; Wu, Dan; Shen, Chaoxuan; Han, Wanqing; Tu, Wanqing; Zeng, Rong

doi:10.1016/j.carbpol.2011.05.026

Cited by 17 publications

(11 citation statements)

References 32 publications

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“…As compared with HA bulk gel, the increase in water swelling ratio of HA-HP hydrogels might be owing to the highly hydrophilic HP with the highest electronegativity among all the polysaccharides and the formation of a looser crosslinked network in the case of more HPGMA feedings. This was similar to our previous HP-functionalized HA microgel, the internal crosslinked network of which got looser at an increasing HP content, so facilitating the water swelling [16]. Therefore, it was believable that the incorporation of HPGMA did have an effect on the crosslinked network and then impacted on the water swelling property of HA-HP hybrid hydrogel.…”

Section: Water Swelling Ratiosupporting

confidence: 87%

“…The loading capacity and release profile of BMP-2 from various hydrogels were performed following our previous work [16]. Briefly, about 10 mg HA-HP hydrogels were soaked in 4 ml binding buffer ( …”

Section: Loading and Delivery Of Bmp-2mentioning

confidence: 99%

“…the conjugation of HP on the surface of amine activated poly(L-lactide-co-glycolic) scaffold for the controlled release of bone morphogenetic protein-2 (BMP-2) in bone tissue engineering [14,15]. In our previous study, by using a microemulsion system we have constructed HP-conjugated HA microgels that proved to efficiently prolong the delivery period of BMP-2 thanks to the interaction between HP and BMP-2 [16]. Therefore, this is expected to realize the GFs sustained release of HA bulk hydrogel as the scaffold material of soft tissue engineering by HP functionalization.…”

Section: Introductionmentioning

confidence: 99%

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Photo-crosslinking hyaluronan-heparin hybrid hydrogels for BMP-2 sustained delivery

Wang

et al. 2016

Journal of Polymer Engineering

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Abstract A series of hyaluronan-heparin (HA-HP) hybrid hydrogels with an HP mass content from 1% to 10% were constructed by photo-crosslinking for the sustained delivery of growth factors (GFs) in soft tissue engineering. Glycidyl methacrylated HA (HAGMA) and glycidyl methacrylated HP (HPGMA) at a substitution degree of 33% and 17%, respectively, by 1H nucleic magnetic resonance (1H NMR) were synthesized and then used for gelation under ultraviolet radiation, followed by various characterizations, including elemental analysis, scanning electron microscopy (SEM), water swelling test, rheological analysis, and bone morphogenetic protein-2 (BMP-2) loading and delivery. The actual contents of HPGMA in HA-HP hydrogels were almost the same as their feeding ratios, indicative of a complete reaction by photo-crosslinking. The incorporation of HP into HA network gently influenced the morphology, water swelling property and rheological properties of hydrogels, but at 10% HP, it doubly increased the BMP-2 loading capacity to 65 ng/mg, alleviated the BMP-2 burst release to 40% within the initial 4 days and prolonged the BMP-2 sustained delivery to over 28 days. These results revealed that the long-term sustained delivery of BMP-2 from HA hydrogel could be achieved by conjugating HP into the crosslinked network with a controllable content.

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Section: Water Swelling Ratiosupporting

confidence: 87%

Section: Loading and Delivery Of Bmp-2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Photo-crosslinking hyaluronan-heparin hybrid hydrogels for BMP-2 sustained delivery

Wang

et al. 2016

Journal of Polymer Engineering

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“…Heparin-mediated delivery of BMP-2 has also resulted in a wide range of effects in vivo, with studies demonstrating variable amounts of mineralization in both ectopic and orthotopic sites [25, 37–39], reflecting an inconsistent ability to form functional bone. Furthermore, the majority of these materials consist of relatively small amounts of heparin immobilized within a larger bulk material [23, 24, 40–43], which may attenuate heparin’s ability to effectively bind and present growth factors. As a result, previous reports on heparin-containing biomaterials may significantly underestimate the amount of BMP-2 that can be delivered via heparin binding.…”

Section: Introductionmentioning

confidence: 99%

Heparin microparticle effects on presentation and bioactivity of bone morphogenetic protein-2

et al. 2014

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Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration.

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“…The water swelling ratio of various HA-based hydrogels was measured gravimetrically [22]. Briefly, the dried hydrogels in certain weight were soaked in phosphate buffer saline (PBS, prepared by mixing 800 ml 0.05 M Na 2 HPO 4 and 200 ml 0.05 M KH 2 PO 4 in a beaker, pH 7.4) at 37°C for 24 h. After the swelling equilibrium was reached, the hydrogels were removed from the medium by centrifugation and weighted after blotting the free liquid on the surface by tissue paper.…”

Section: Water Swelling Measurementsmentioning

confidence: 99%

Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

Luo

Wang

et al. 2015

Materials Science and Engineering: C

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Preparation, structure and BMP-2 controlled release of heparin-conjugated hyaluronan microgels

Cited by 17 publications

References 32 publications

Photo-crosslinking hyaluronan-heparin hybrid hydrogels for BMP-2 sustained delivery

Photo-crosslinking hyaluronan-heparin hybrid hydrogels for BMP-2 sustained delivery

Heparin microparticle effects on presentation and bioactivity of bone morphogenetic protein-2

Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

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