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Review
. 2014 Apr;10(4):1588-600.
doi: 10.1016/j.actbio.2013.07.031. Epub 2013 Aug 2.

Heparin-functionalized polymeric biomaterials in tissue engineering and drug delivery applications

Yingkai Liang  1 , Kristi L Kiick  2
Affiliations
Review

Heparin-functionalized polymeric biomaterials in tissue engineering and drug delivery applications

Yingkai Liang et al. Acta Biomater. 2014 Apr.

Abstract

Heparin plays an important role in many biological processes via its interaction with various proteins, and hydrogels and nanoparticles comprising heparin exhibit attractive properties, such as anticoagulant activity, growth factor binding, and antiangiogenic and apoptotic effects, making them great candidates for emerging applications. Accordingly, this review summarizes recent efforts in the preparation of heparin-based hydrogels and formation of nanoparticles, as well as the characterization of their properties and applications. The challenges and future perspectives for heparin-based materials are also discussed. Prospects are promising for heparin-containing polymeric biomaterials in diverse applications ranging from cell carriers for promoting cell differentiation to nanoparticle therapeutics for cancer treatment.

Keywords: Drug delivery; Heparin; Hydrogels; Nanoparticles; Tissue engineering.

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Figures

Fig. 1
Fig. 1
Major (ca. 85%) and minor (ca. 15%) disaccharide sequences of heparin.
Fig 2
Fig 2
Cell-mediated delivery and targeted erosion of growth factor-crosslinked hydrogels. i) Schematic of non-covalently assembled hydrogel formed by the crosslinking of polysaccharide-derivatized star copolymers by dimeric, heparin-binding growth factors, followed by receptor-mediated erosion. ii) The release profile of VEGF from non-covalently assembled [PEG-LMWH/VEGF] hydrogels. Release profiles of VEGF in the presence of PAE/KDR (●) or PAE (■) cells, and in the absence of cells (▲), respectively. *p<0.002; **p<0.004. Reprinted with permission from [48], copyright (2010) John Wiley and Sons.
Fig. 3
Fig. 3
Dual growth factor delivery from star PEG-heparin hydrogels. i) Design of star poly(ethylene glycol)–heparin hydrogels showing decoupled mechanical and modular biomolecular characteristics. ii)Interactions of differently modified hydrogels on the different substrates. (A): representative fluorescence microscopy images after live/dead staining of HUVECs (scale bar 130 μm); (B): HUVECs proliferation/survival as accessed via cell numbers quantified by an MTT assay; (C): HUVECs morphology as accessed via cell circularity by the circularity calculation within ImageJ. Reprinted with permission from [66], copyright (2010) Elsevier and [67], copyright (2011) Elsevier.
Fig. 4
Fig. 4
GSH-responsive PEG-LMWH hydrogels via reversible maleimide–thiol Michael-type addition. i)Conversion of retro-Michael adducts formed with Michael donors of different reactivity. ii) Schematic representation of the formation and degradation of GSH-responsive PEG-LMWH hydrogels. iii) Comparison of storage moduli for select degrading hydrogels: PEG–SH hydrogel (★) LMWH–PEG–MPP (●) and –DMMPP (■) under high reducing conditions (10mM GSH) and LMWH–PEG–MPP (○) under standard reducing conditions (10μM GSH). Reprinted with permission from [90], copyright (2011) American Chemical Society and [91], copyright (2013) The Royal Society of Chemistry.
Fig. 5
Fig. 5
Schematic of polyelectrolyte self-assembly of heparinized CS/γ-PGA nanoparticles (HP-CS/γ-PGA NPs) and release of bFGF or heparin from the nanoparticles, depending on the environmental pH. Reprinted with permission from [108], copyright (2010) Elsevier.
Fig. 6
Fig. 6
Intracellular delivery of reducible heparin nanogels for apoptotic cell death. i) Synthetic scheme of disulfide crosslinked heparin nanogels. ii) (A) Dose-dependent anti-proliferative effect of heparin nanogels against mouse melanoma B16F10 cells after 3 days; (B) Growth profiles of B16F10 cells cultured in the presence of heparin or heparin nanogels. Reprinted with permission from [114], copyright (2008) Elsevier.
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References

    1. Capila I, Linhardt RJ. Heparin - protein interactions. Angew Chem Int Ed. 2002;41:391–412. - PubMed
    1. Linhardt RJ. 2003 Claude S. Hudson Award address in carbohydrate chemistry. Heparin: structure and activity. J Med Chem. 2003;46:2551–64. - PubMed
    1. Rabenstein DL. Heparin and heparan sulfate: structure and function. Nat Prod Rep. 2002;19:312–31. - PubMed
    1. Gospodarowicz D, Cheng J. Heparin protects basic and acidic FGF from inactivation. J Cell Physiol. 1986;128:475–84. - PubMed
    1. Kharkar PM, Kiick KL, Kloxin AM. Designing degradable hydrogels for orthogonal control of cell microenvironments. Chem Soc Rev. Advance Article. 2013 DOI: 10.1039/C3CS60040H. - PMC - PubMed

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