Elsevier

Carbohydrate Polymers

Volume 114, 19 December 2014, Pages 458-466
Carbohydrate Polymers

Structural analysis of dextrins and characterization of dextrin-based biomedical hydrogels

https://doi.org/10.1016/j.carbpol.2014.08.009Get rights and content

Highlights

  • Structural characterization of dextrins.

  • Development of injectable dextrin-based hydrogels.

  • Characterization of hydrogels with functional and bioactive features.

Abstract

The characterization of several commercial dextrins and the analysis of the potential of dextrin derived hydrogels for biomedical applications were performed in this work. The structural characterization of dextrins allowed the determination of the polymerization and branching degrees, which ranged from 6 to 17 glucose residues and 2 to 13%, respectively. Tackidex, a medical grade dextrin was choosen for further characterization.

The combination of hydrogel with a dextrin nanogel and urinary bladder matrix was achieved without compromising the mechanical properties or microstructure. The encapsulation of cells, preserving its viability, confirms the biocompatibility of the injectable hydrogels, which have therefore great potential for biomedical applications.

Introduction

Dextrins are a class of low molecular weight carbohydrates produced by acid or/and enzymatic partial hydrolysis of starch or glycogen, thus exhibiting the α-(1  4)-Glc structure of amylose and the α-(1  4)- and α-(1  4,6)-Glc branched structure of amylopectin, but with lower polymerization. The extent of hydrolysis is expressed in terms of “dextrose equivalent” (DE), a measure of the total reducing power (Chronakis, 1998, White et al., 2003). Dextrins with the same DE can display differences in terms of hygroscopicity, fermentability, viscosity, sweetness, stability, gelation, solubility, and bioavailability, which may be assigned to distinct structural features (Chronakis, 1998). Depending on the source of the native starch, as well as on the hydrolysis conditions, several types of dextrins can be obtained, displaying different properties that can be suited for specific applications.

Dextrins are an affordable raw material, generally regarded as safe (GRAS) (Alvani, Qi, & Tester, 2011). It is a widely used material with a great variety of applications such as adhesives, foods, textiles and cosmetics (Gonçalves, Moreira, Carvalho, Silva, & Gama, 2014). Regarding biomedical applications, dextrin is yet relatively unexplored, being clinically used as a peritoneal dialysis solution that can also perform as a drug delivery solution (Peers and Gokal, 1998, Takatori et al., 2011) and as wound dressing agent (DeBusk & Alleman, 2006). Although its limited number of current biomedical applications, dextrin exhibit a set of advantages that potentiates its use specifically in the biomaterials field. It is a biocompatible and non-immunogenic material, degradable in vivo by α-amylases and its molecular weight ensures renal elimination avoiding tissue accumulation due to repeated administration (Hreczuk-Hirst et al., 2001, Moreira et al., 2010).

Hydrogels are three-dimensional, hydrophilic and polymeric networks that are highly hydrated and are receiving attention as scaffold materials (Drury and Mooney, 2003, Hoffman, 2002). The relevance of injectable hydrogels for biomedical purposes has increased in the last years since they generally are biocompatible, biodegradable, exhibit mechanical and structural properties that resembles extracellular matrix, are processed under mild conditions and enable less invasive clinical procedures (Drury and Mooney, 2003, Hoffman, 2002, Van Vlierberghe et al., 2011). Hydrogels can be used alone or in combination with other components (e.g. cells, drugs, DNA, signalling molecules) (Jagur-Grodzinski, 2010, Peppas et al., 2006).

Several dextrin-based hydrogels, obtained by radical polymerization have been reported (Carvalho et al., 2007, Carvalho et al., 2009, Das et al., 2013, Das et al., 2014, Moreira et al., 2010). Also, an oxidized dextrin hydrogel cross-linked with adipic acid dihydrazide was described by our group (Molinos, Carvalho, Silva, & Gama, 2012). Adipic acid dihydrazide may be used to promote the reticulation of polysacharide-based hydrogels, such as oxidized dextran (Maia, Ferreira, Carvalho, Ramos, & Gil, 2005), hyaluronic acid (Schramm et al., 2012);(Su, Chen, & Lin, 2010), poly(aldehyde guluronate) (Bouhadir, Hausman, & Mooney, 1999), among others. Despite the overall good biocompatibility, Schramm et al. (2012) reported a mild cytotoxic effect of the dihydrazide-reticulated hydrogels. However, information about the biocompatibility of non-crosslinked monomer is very scarce. This work provides a comprehensive structural characterization of several commercial dextrins, which were used to produce oxidized dextrin hydrogels reticulated with adipic acid dihydrazide. The cytotoxicity of the crosslinking agent was evaluated and compared with that of glutaraldehyde. The later is a widely used crosslinker, often considered cytotoxic (Huang-Lee et al., 1990, Mcpherson et al., 1986), but still used for reticulation of biomedical products (Furst & Banerjee, 2005).

Section snippets

Materials

All reagents used were of laboratory grade and purchased from Sigma-Aldrich, unless stated otherwise. Koldex 60 dextrin was a gift from Tate & Lyle. Tackidex was a gift from Roquette. Dextrins w28, w35, w60 and w80 were a gift from Avebe. Icodextrin and D4894 were obtained from Baxter and Sigma, respectively. All other chemicals and solvents used in this work were of the highest purity commercially available.

Structural analysis of dextrins

Neutral sugars were determined as alditol acetates as described by Nunes et al. (2012).

Structural dextrin analysis

The dextrins used in this work are commercially available products. These materials are not sufficiently characterized, and as it will be shown, some of the available information is equivocal. In this work, we aimed at correlating the dextrin's structural differences with the properties of the derived hydrogels. All dextrin's analysed were composed only by glucose, as confirmed by sugar methylation analysis, which revealed the presence of (1  4)-, terminally-, and (1  4,6)-linked Glcp residues in

Conclusions

The structural characterization showed that dextrins from different sources displayed structural differences, namely regarding chain length and branching degree. The molecular weight of dextrins is much lower than the values often reported in the literature, commonly obtained by SEC. However, these differences do not seem to influence the gelation and degradation of the hydrogels. The combination with a dextrin nanogel and urinary bladder matrix was successfully achieved. The cytotoxicity of

Acknowledgments

D.M.S. was supported by the grant SFRH/BD/64571/2009 from Fundação para a Ciência e Tecnologia (FCT), Portugal. We thank FCT funding through EuroNanoMed ENMED/0002/2010. The authors acknowledge the funding from QREN (“Quadro de Referência Estratégica Nacional”) and ADI (“Agência de Inovação”) through the project Norte-07-0202-FEDER-038853.

QOPNA research unit is funded by Fundação para a Ciência e a Tecnologia (FCT, Portugal, European Union, QREN, FEDER, and COMPETE (project

References (51)

  • C. Goncalves et al.

    Characterization of the self-assembly process of hydrophobically modified dextrin

    European Polymer Journal

    (2008)
  • A.S. Hoffman

    Hydrogels for biomedical applications

    Advanced Drug Delivery Reviews

    (2002)
  • D. Hreczuk-Hirst et al.

    Dextrins as potential carriers for drug targeting: Tailored rates of dextrin degradation by introduction of pendant groups

    International Journal of Pharmaceutics

    (2001)
  • C.R. Lee et al.

    The effects of cross-linking of collagen-glycosaminoglycan scaffolds on compressive stiffness, chondrocyte-mediated contraction, proliferation and biosynthesis

    Biomaterials

    (2001)
  • Y. Liu et al.

    Hydrogel based on interpenetrating polymer networks of dextran and gelatin for vascular tissue engineering

    Biomaterials

    (2009)
  • J. Maia et al.

    Synthesis and characterization of new injectable and degradable dextran-based hydrogels

    Polymer

    (2005)
  • C. Nunes et al.

    Occurrence of cellobiose residues directly linked to galacturonic acid in pectic polysaccharides

    Carbohydrate Polymers

    (2012)
  • C.P. Passos et al.

    Sequential microwave superheated water extraction of mannans from spent coffee grounds

    Carbohydrate Polymers

    (2014)
  • M.T. Sheu et al.

    Characterization of collagen gel solutions and collagen matrices for cell culture

    Biomaterials

    (2001)
  • W.Y. Su et al.

    Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration

    Acta Biomaterialia

    (2010)
  • D.R. White et al.

    Dextrin characterization by high-performance anion-exchange chromatography–pulsed amperometric detection and size-exclusion chromatography–multi-angle light scattering–refractive index detection

    Journal of Chromatography A

    (2003)
  • R. Zhang et al.

    A novel pH- and ionic-strength-sensitive carboxy methyl dextran hydrogel

    Biomaterials

    (2005)
  • K. Alvani et al.

    Use of carbohydrates, including dextrins, for oral delivery

    Starch-Starke

    (2011)
  • S.F. Badylak et al.

    Whole-organ tissue engineering: Decellularization and recellularization of three-dimensional matrix scaffolds

    Annual Review of Biomedical Engineering

    (2011)
  • I.S. Chronakis

    On the molecular characteristics, compositional properties, and structural–functional mechanisms of maltodextrins: A review

    Critical Reviews in Food Science and Nutrition

    (1998)
  • Cited by (33)

    • Injectable nanocomposite hydrogels as an emerging platform for biomedical applications: A review

      2021, Materials Science and Engineering C
      Citation Excerpt :

      Nevertheless, the biological assessments of the resulting nanocomposite remained to be conducted to verify its actual appropriateness for biomedical applications [170]. Dextrins are low molecular weight carbohydrates prepared by partial hydrolysis of starch or glycogen, hence presenting the α-(1 → 4)-Glc structure of amylose and the α-(1 → 4)- and α-(1 → 4,6)-Glc branched structure of amylopectin, but with lower polymerization [171]. Cyclodextrins (CDs) are a cyclical form of dextrins and exist in various subtypes, including αCD, βCD, and γCD, which consist of 6, 7, and 8 d-glucose units, respectively.

    • Dynamic covalent constructed self-healing hydrogel for sequential delivery of antibacterial agent and growth factor in wound healing

      2019, Chemical Engineering Journal
      Citation Excerpt :

      Other chemical reagents were of analytical grade. NGel and ODex were prepared according to the previously reported method [14,19], and the details were described in Supplementary data. Next, 20 wt% NGel, 20 wt% ODex, and 5 wt% ADH solutions were separately prepared in PBS (pH 7.4) at room temperature (RT).

    View all citing articles on Scopus
    1

    Contributed equally to this study.

    View full text