Enzymatically Cross-Linked Bovine Lactoferrin as Injectable Hydrogel for Cell Delivery

Amini, Ashley A.; Kan, Ho-Man; Cui, Zhanwu; Maye, Peter; Nair, Lakshmi S.

doi:10.1089/ten.tea.2013.0506

Cited by 14 publications

(11 citation statements)

References 36 publications

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“…[10][11][12] Among these, enzyme catalyzed crosslinking of polymers using peroxidases such as horse radish peroxidase (HRP) is one of the most extensively investigated approaches. [13][14][15][16][17] Both natural and synthetic polymers containing phenol groups or those functionalized with tyramine, tyrosine or other aminophenol molecules can be cross-linked effectively using peroxidases. 18 Briefly, in the presence of hydrogen peroxide (H 2 O 2 ) and HRP, the phenolic groups in the polymers undergo one-electron oxidation and generate reactive radical groups which subsequently react with each other to form the cross-linked hydrogel.…”

Section: Introductionmentioning

confidence: 99%

“…17,19 The in vitro and in vivo biocompatibility of peroxidase crosslinked hydrogels has been demonstrated using a wide range of polymers. 4,13,17,[20][21][22] Chitosan is a natural, hydrophilic, polysaccharide extensively studied as a biomaterial due to its non-toxic, biocompatible and biodegradable properties. [23][24][25] It is a linear co-polymer consisting of ß(1-4)-linked glucosamine units and N-acetyl glucosamine units.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of enzymatically crosslinked injectable glycol chitosan hydrogel

et al. 2015

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Enzymatically cross-linkable phenol-conjugated glycol chitosan was prepared by reacting glycol chitosan with 3-(4-hydroxyphenyl)propionic acid (HPP). The chemical modification was confirmed by FTIR, 1 H-NMR and UV spectroscopy. Glycol chitosan hydrogels (HPP-GC) with or without rhBMP-2 were prepared by the oxidative coupling of the substituted phenol groups in the presence of hydrogen peroxide and horse radish peroxidase. Rheological characterization demonstrated the feasibility of developing hydrogels with varying storage moduli by changing the polymer concentration. The gel presented a microporous structure with pore sizes ranging from 50-350 mm. The good viability of encapsulated 7F2 osteoblasts indicated non-toxicity of the gelation conditions. In vitro release of rhBMP-2 in phosphate buffer solution showed B11% release in 360 h. The ability of the hydrogel to maintain the in vivo bioactivity of rhBMP-2 was evaluated in a bilateral critical size calvarial bone defect model in Col3.6 transgenic fluorescent reporter mice. The presence of fluorescent green osteoblast cells with overlying red alizarin complexone and yellow stain indicating osteoclast TRAP activity confirmed active cell-mediated mineralization and remodelling process at the implantation site. The complete closure of the defect site at 4 and 8 weeks post implantation demonstrated the potent osteoinductivity of the rhBMP-2 containing gel.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of enzymatically crosslinked injectable glycol chitosan hydrogel

et al. 2015

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“…In this scenario, the functionalization of biomimetic HA nanocrystals with LF could be an innovative strategy to set up a novel functional biomaterial aiming to reduce the imbalance in bone homeostasis occurring in osteoporosis. The rationale behind the development of HA-LF system is that the association of the peculiar properties of each components, such as the well-known osteoconductive properties of biomimetic HA and its role in the induction of the osteogenetic related genes expression, with the bioactivity of LF [ 14 , 19 ], could act in synergism to promote the activation of bone-forming OBs and to inhibits bone—resorbing OCLs. In previous studies we have demonstrated that the conjugation of HA with LF is strong and stable and leads to a combined effect in the induction of osteogenic differentiation of mesenchymal stem cells (MSCs) [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Coupling Hydroxyapatite Nanocrystals with Lactoferrin as a Promising Strategy to Fine Regulate Bone Homeostasis

et al. 2015

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Lactoferrin (LF) is an interesting glycoprotein in the field of bone biology for its regulatory effect on cells involved in bone remodeling, that results compromised in several pathological conditions, as osteoporosis. In a previous study we observed that the coupling of LF and biomimetic hydroxyapatite nanocrystals (HA), a material well-known for its bioactivity and osteoconductive properties, leads to a combined effect in the induction of osteogenic differentiation of mesenchymal stem cells. On the basis of this evidence, the present study is an extension of our previous work aiming to investigate the synergistic effect of the coupling of HA and LF on bone homeostasis. Biomimetic HA nanocrystals were synthesized and functionalized with LF (HA-LF) and then pre-osteoblasts (MC3T3-E1) and monocyte/macrophage cells lines (RAW 264.7), using as osteoclastogenesis in vitro model, were cultured separately or in co-culture in presence of HA-LF. The results clearly revealed that HA and LF act in synergism in the regulation of the bone homeostasis, working as anabolic factor for osteoblasts differentiation and bone matrix deposition, and as inhibitor of the osteoclast formation and activity.

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“…A remarkable increased expression of ERK (a proliferation marker) and RunX2 (a differentiation marker) was observed in the encapsulated MC3T3 cells. The cells maintained their differentiation ability as revealed by expression of collagen I protein, and osteocalcin after 21 days post culture in mineralization media [ 218 , 219 ]. A number of studies suggested that Lf-induced osteogenic activity and proliferation of osteoblasts may be mediated by binding with TGF-β receptors and stimulating TGF-β canonical pathways, or by activation of MAPK pathways [ 220 ].…”

Section: Pharmaceutical Applicationsmentioning

confidence: 99%

Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand

et al. 2020

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Recent progress in protein-based nanomedicine, inspired by the success of Abraxane® albumin-paclitaxel nanoparticles, have resulted in novel therapeutics used for treatment of challenging diseases like cancer and viral infections. However, absence of specific drug targeting, poor pharmacokinetics, premature drug release, and off-target toxicity are still formidable challenges in the clinic. Therefore, alternative protein-based nanomedicines were developed to overcome those challenges. In this regard, lactoferrin (Lf), a glycoprotein of transferrin family, offers a promising biodegradable well tolerated material that could be exploited both as an active therapeutic and drug nanocarrier. This review highlights the major pharmacological actions of Lf including anti-cancer, antiviral, and immunomodulatory actions. Delivery technologies of Lf to improve its pries and enhance its efficacy were also reviewed. Moreover, different nano-engineering strategies used for fabrication of drug-loaded Lf nanocarriers were discussed. In addition, the use of Lf for functionalization of drug nanocarriers with emphasis on tumor-targeted drug delivery was illustrated. Besides its wide application in oncology nano-therapeutics, we discussed the recent advances of Lf-based nanocarriers as efficient platforms for delivery of anti-parkinsonian, anti-Alzheimer, anti-viral drugs, immunomodulatory and bone engineering applications.

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Enzymatically Cross-Linked Bovine Lactoferrin as Injectable Hydrogel for Cell Delivery

Cited by 14 publications

References 36 publications

Evaluation of enzymatically crosslinked injectable glycol chitosan hydrogel

Evaluation of enzymatically crosslinked injectable glycol chitosan hydrogel

Coupling Hydroxyapatite Nanocrystals with Lactoferrin as a Promising Strategy to Fine Regulate Bone Homeostasis

Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand

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