Article

Angiogenic potential of gellan-gum-based hydrogels for application in nucleus pulposus regeneration: In vivo study

Department of Polymer Engineering, 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.
Tissue Engineering Part A (Impact Factor: 4.64). 03/2012; 18(11-12):1203-12. DOI: 10.1089/ten.TEA.2011.0632
Source: PubMed

ABSTRACT Hydrogels for nucleus pulposus (NP) regeneration should be able to comprise a nonangiogenic or even antiangiogenic feature. Gellan gum (GG)-based hydrogels have been reported to possess adequate properties for being used as NP substitutes in acellular and cellular strategies, due to its ability to support cell encapsulation, adequate mechanical properties, and noncytotoxicity. In this study, the angiogenic response of GG-based hydrogels was investigated by performing the chorioallantoic membrane assay. The convergence of macroscopic blood vessels toward the GG, ionic-crosslinked methacrylated GG (iGG-MA), and photo-crosslinked methacrylated GG (phGG-MA) hydrogel discs was quantified. Gelatin sponge (GSp) and filter paper (FP) alone and with vascular endothelial growth factor were used as controls of angiogenesis. The images obtained were digitally processed and analyzed by three independent observers. The macroscopic blood vessel quantification demonstrated that the GG-based hydrogels are not angiogenic as compared with FP controls. No statistical differences between the GG-based hydrogels tested in respect to its angiogenic ability were observed. Hematoxylin and eosin staining and SNA-lectin immunohistochemistry assay indicated that the iGG-MA and phGG-MA hydrogels do not allow the ingrowth of chick endothelial cells, following 4 days of implantation. On the contrary, GG, GSp, and FP controls allowed cell infiltration. The histological data also indicated that the GG-based hydrogels do not elicit any acute inflammatory response. The results showed that the GG, iGG-MA, and phGG-MA hydrogels present different permeability to cells but functioned as a physical barrier for vascular invasion. These hydrogels present promising and tunable properties for being used as NP substitutes in the treatment of degenerative intervertebral disc.

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    • "For NP regeneration alone, numerous hydrogels have been developed to support native NP cells (NPCs) (i.e., acellular scaffolds, or for carrying mesenchymal stem cells or NPCs, alginate [14], carboxymethylcellulose [12], and hyaluronan [11], among others [1] [2]). Methacrylated gellan gum (GG- MA) hydrogels have been suggested as a suitable platform both to support NPCs and to avoid angiogenesis, which contributes to maintaining hypoxia levels inside the NP, thus stimulating NPC's phenotype [18] [19]. "
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    • "When compared to other animal-extracted, natural polymers, for instance the hyaluronic acid extracted from rooster combs [17], it represents a lower risk of disease transmission. So far, the possibility of tuning GG hydrogels in terms of cross-linking degree and related mechanical properties, as well as their ability for in situ gelation, has allowed GG hydrogels to be proposed for different regenerative medical applications [18] [19] [20] [21]. On the other hand, like most natural polymers [22], its relatively poor mechanical properties narrow the scope of its applications in tissue engineering [23]. "
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    • "The value of Young's modulus was similar to the value reported for human nucleus pulposus (Leahy and Hukins, 2001). It was also shown that methacrylated gellan protected nucleus pulposus by acting as a barrier for angiogenesis (Silva-Correia et al., 2012). Shin et al. (2012) designed hydrogels for encapsulation of human fibroblasts consisting of two interpenetrating networks of methacrylated gellan gum and methacrylated gelatin. "
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