Gellan gum‐hydroxyapatite composite spongy‐like hydrogels for bone tissue engineering

Abstract

Osteoinductive biomaterials represent a promising approach to advance bone grafting. Despite promising, the combination of sustained biodegradability, mechanical strength, and biocompatibility in a unique biomaterial that can also support cell performance and bone formation in vivo is demanding. Herein, we developed gellan gum (GG)-hydroxyapatite (HAp) spongy-like hydrogels to mimic the organic (GG) and inorganic (HAp) phases of the bone. HAp was successfully introduced within the GG polymeric networks, as determined by FTIR and XRD, without compromising the thermostability of the biomaterials, as showed by TGA. The developed biomaterials showed sustained degradation, high swelling, pore sizes between 200 and 300 μm, high porosity (>90%) and interconnectivity (<60%) that was inversely proportional to the total polymeric amount and to CaCl crosslinker. CaCl and HAp reinforced the mechanical properties of the biomaterials from a storage modulus of 40 KPa to 70-80 KPa. This study also showed that HAp and CaCl favored the bioactivity and that cells were able to adhere and spread within the biomaterials up to 21 days of culture. Overall, the possibility to tailor spongy-like hydrogels properties by including calcium as a crosslinker and by varying the amount of HAp will further contribute to understand how these features influence bone cells performance in vitro and bone formation in vivo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 479-490, 2018.

Biological Role of Gellan Gum in Improving Scaffold Drug Delivery, Cell Adhesion Properties for Tissue Engineering Applications

“…The mechanical properties of the GG are improved by combining it with inorganic materials (for their flexibility), and biopolymers (with poor rigidity) became common and smart solutions to improve the mechanical properties of GG. Composites of GG have been recently accomplished by the introduction of hydroxyapatite (HAp) [31], bioactive glass [32,33], calcium phosphate (CaP) [34], hyaluronic acid (HA) [35], demineralized bone powder (DBP) [36], polyethylene glycol [37], silk fibrin [38], agar [39], saponin [40], and chondroitin sulfate [41]. Table 1 shows the different types of GG composites that are used for biological applications.…”

Natural Polymeric Scaffolds in Bone Regeneration

“…Based on direct mixing and co-precipitation principles respectively, the suspension and immersion techniques are the main manufacturing methods to integrate bioceramics into collagen (Kikuchi et al, 2004;Yunoki et al, 2007;Xia et al, 2016). -Need for determining aquaculture systems or farming (when ex situ cultivation is difficult) -Species-dependent variability of characteristics and composition (Green et al, 2003;Granito et al, 2016) Heparin -Preserve the growth factor stability and bioactivity -Reduced cell growth rate (Chung and Park, 2007) Polysaccharide-based polymers (Khan and Ahmad, 2013;Sofi et al, 2018) Carrageenans-High molecular flexibility -Thixotropic nature -Gel dissolution in the absence of a gel-inducing reagent -Elevated melting temperature (Garg et al, 2012;Yegappan et al, 2019) Gellan gum -Resistance to acidic conditions and high temperature -Transparency, flexibility and elasticity in the highly acylic gels -Low elasticity and brittleness when used in the low acyl form (Pereira et al, 2013;Manda et al, 2018) Some examples of collagen biocomposites and related properties are reported in Table 4. It is well-established that adding HA not only increases the compression modulus of collagen scaffolds, but also provides a larger and rougher adherence surface allowing for improved adhesion, bioactivity, and proliferation of cells (Sionkowska and Kozlowska, 2013).…”

“…Gellan gum derived from bacterial fermentation (Sphingomonas group) forms injectable and thermoreversible hydrogels with tunable mechanical properties useful for preparation of bilayered scaffolds for osteochondral regeneration (Pereira et al, 2013;Manda et al, 2018).…”

Recent Advances in Natural Gum-Based Biomaterials for Tissue Engineering and Regenerative Medicine: A Review

“…Both Ca 2+ and HAp improved the mechanical stability of the hydrogels (storage modulus: 40-80 kPa). In addition, hydrogels showed good bioactivity and bone cell attachment and spreading within the hydrogels up to 21 days of cell culture [157]. Further, ALP, an enzyme that is involved in the biomineralization of bone by cleaving phosphate from organic phosphate, was incorporated in GeG hydrogels to induce biomineralization with calcium phosphate (CaP).…”