Elsevier

Biomaterials

Volume 26, Issue 15, May 2005, Pages 2455-2465
Biomaterials

Controlling alginate gel degradation utilizing partial oxidation and bimodal molecular weight distribution

https://doi.org/10.1016/j.biomaterials.2004.06.044Get rights and content

Abstract

Degradability is often a critical property of materials utilized in tissue engineering. Although alginate, a naturally derived polysaccharide, is an attractive material due to its biocompatibility and ability to form hydrogels, its slow and uncontrollable degradation can be an undesirable feature. In this study, we characterized gels formed using a combination of partial oxidation of polymer chains and a bimodal molecular weight distribution of polymer. Specifically, alginates were partially oxidized to a theoretical extent of 1% with sodium periodate, which created acetal groups susceptible to hydrolysis. The ratio of low MW to high MW alginates used to form gels was also varied, while maintaining the gel forming ability of the polymer. The rate of degradation was found to be controlled by both the oxidation and the ratio of high to low MW alginates, as monitored by the reduction of mechanical properties and corresponding number of crosslinks, dry weight loss, and molecular weight decrease. It was subsequently examined whether these modifications would lead to reduced biocompatibility by culturing C2C12 myoblast on these gels. Myoblasts adhered, proliferated, and differentiated on the modified gels at a comparable rate as those cultured on the unmodified gels. Altogether, this data indicates these hydrogels exhibit tunable degradation rates and provide a powerful material system for tissue engineering.

Section snippets

1. Introduction

Tissue engineering provides an alternative to traditional approaches (e.g., transplantation) to replace lost tissues or whole organ function [1]. This approach often utilizes a combination of tissue-specific cells, polymeric scaffolds, and signals, both chemical and mechanical to guide cell phenotype [2]. Frequently, specific cell types are isolated, expanded in vitro, and subsequently incorporated into three-dimensional scaffolds, and the cell-scaffold construct is introduced to a wound site.

2.1. Alginate modification

Sodium alginate powder rich in GG-blocks (MVG, Pronova, Mw=2.7×105 g/mol) was used as the high molecular weight component (abbreviated as HMW) to form gels. Low molecular weight alginate (Mw=5.3×104 g/mol, abbreviated as LMW) was obtained by gamma (γ)-irradiating HMW with a cobalt-60 source for 4 h at a γ-dose of 5.0 Mrad, as specified by Kong et al. [14]. In certain experiments, alginates (both LMW and HMW) were diluted to 1% w/v in ddH2O, and 1% of the sugar residues were oxidized with sodium

3. Results

To create alginate that is hydrolytically labile, the polymer was oxidized to a theoretical extent at 1% using sodium periodate. Measurement of the actual aldehyde content revealed an extent of oxidation of 0.93±0.1%. These oxidized and non-oxidized alginate were subsequently used to form hydrogels, in which the varying ratio of HMW and LWM polymer were combined (WLMW=weight fraction of LMW alginate in gels). The three specific hydrogel systems tested were partially oxidized binary gel (1%

4. Discussion

Combining partial oxidation and a controlled molecular weight distribution allows one to control alginate hydrogel degradation. Partial oxidation has been previously employed to trigger alginate degradation through hydrolytic scission. Our results (Fig. 2, Fig. 3, Fig. 7) were consistent with previous studies, as the partially oxidized unary alginate gels degraded, as indicated by their decrease in mechanical properties, dry mass, and molecular weight. Despite using high molecular weight

5. Conclusions

Partial oxidation and bimodal molecular weight distribution were successfully combined to regulate alginate gel degradation. The mechanism of the degradation was found to be mainly due to hydrolytic chain scission. These modified alginates maintained favorable cell interactions, as the ability of myoblasts to proliferate and differentiate when cultured on partially oxidized binary and unary alginates was comparable to those on non-oxidized unary gels. Altogether, these alginate hydrogels with

Acknowledgements

The author would like to thank NIDCR/NIH for financial support (RO1 DE13349), as well as Royal King Anandamahidol foundation (Thailand) for a graduate fellowship to T.B.

References (32)

  • K.A. Beningo et al.

    Flexible substrata for the detection of cellular traction forces

    Trends Cell Biol

    (2002)
  • M. Opas

    Expression of the differentiated phenotype by epithelial cells in vitro is regulated by both biochemistry and mechanics of the substratum

    Dev Biol

    (1989)
  • A. Persidis

    Tissue engineering

    Nat Biotech

    (1999)
  • L.G. Griffith

    Emerging design principles in biomaterials and scaffolds for tissue engineering

    Ann NY Acad Sci

    (2002)
  • D.J. Mooney et al.

    Growing new organs

    Sci Am

    (1999)
  • K.Y. Lee et al.

    Hydrogels for tissue engineering

    Chem Rev

    (2001)
  • Cited by (0)

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