Alginate/hydroxyapatite hydrogel as biodegradable in situ forming scaffold
The injectable polymer scaffolds are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural proteins and polysaccharides are ideal tissue engineering scaffolds since they resemble the extracellular matrices of the
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INTRODUCTION Hydrogels are appealing scaffold materials due to their high water content, good biocompatibility and consistency similar to soft tissue. They play important role in several applications including tissue engineering and controlled delivery of therapeutic agents. The simplest and the most convenient approach in these applications will be to inject the polymer-cell or drug entity into the body in a minimally invasive manner. Naturally derived hydrogels resemble the nature extracellular matrix and thus have the potential to direct the migration, growth and organization of cells during tissue regeneration and wound healing and for stabilization of encapsulated and transplanted cells. Alginate is a natural biomacromolecule isolated from seaweed and bacteria. It is consisting of (1o4) linked E-Dmannuronate (M) and its C-5 epimer D-L-guluronate (G) residues arranged in blocks of M fragments, G fragments, and alternating G and M fragments [1]. It is an important naturally produced material which can forms wellcharacterized hydrogels by adding divalent cations (except
Mg2+) under physiological conditions [2]. The use of alginate scaffolds in tissue-engineering applications is limited owing to their weak mechanical properties, lack of cellular interactions, and uncontrollable degradation [3]. For these reasons, covalent crosslinking has been investigated in order to impart controlled mechanical properties to the alginate hydrogels [4]. However almost of the synthetic processes include using toxic reagents. The present study shows an injectable, nontoxic, biodegradable hydrogel scaffold prepared by crosslinking of oxidized alginate and Hydroxyapatite (HA), in the presence of small concentrations of D-glucono-G-lactone (GDL). Partially oxidized alginate is degradable and still capable of being ionically cross-linked with calcium ions to form hydrogel [5]. HA (Ca10(PO4)6(OH)2) is a calcium phosphate salt and being used as an artificial bone material due to its biocompatibility, bioactivity, osteoconductivity, nontoxicity, noninflammatory behavior. Some investigators have reported that HA may bond directly with host bone [6]. GDL is the oxidation product of gluconic acid and widely used as a coagulation, acidulant, leavening agent and sequestrant in human food. Up to now, GDL does not seem to have any obvious toxic effects on human body, and some investigators have reported that GDL showed inhibitory effects on common pathogen icorganisms[7].
II. MATERIALS AND METHODS A. Alginate/hydroxyapatite hydrogel preparation Sodium alginate sample (Crystal Rock Biology Development Company, China) was purified by precipitating with absolute ethanol. Partially oxidized alginate sample with 3% degree of oxidation was prepared by adding sodium metaperiodate solutions into the alginate/ethanol suspension and stirred in the dark magnetically at 25oC for 10 hours[8]. After reaction, the solutions were dialyzed against distilled water using cellulose tubular membranes (cut-off molecular weight is ~12000) until the dialyzate was peri
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