Injectable self-gelling composites for bone tissue engineering based on gellan gum hydrogel enriched with different bioglasses

Abstract

Hydrogels of biocompatible calcium-crosslinkable polysaccharide gellan gum (GG) were enriched with bioglass particles to enhance (i) mineralization with calcium phosphate (CaP); (ii) antibacterial properties and (iii) growth of bone-forming cells for future bone regeneration applications. Three bioglasses were compared, namely one calcium-rich and one calcium-poor preparation both produced by a sol-gel technique (hereafter referred to as A2 and S2, respectively) and one preparation of composition close to that of the commonly used 45S5 type (hereafter referred to as NBG). Incubation in SBF for 7 d, 14 d and 21 d caused apatite formation in bioglass-containing but not in bioglass-free samples, as confirmed by FTIR, XRD, SEM, ICP-OES, and measurements of dry mass, i.e. mass attributable to polymer and mineral and not water. Mechanical testing revealed an increase in compressive modulus in samples containing S2 and NBG but not A2. Antibacterial testing using biofilm-forming meticillin-resistant staphylococcus aureus (MRSA) showed markedly higher antibacterial activity of samples containing A2 and S2 than samples containing NBG and bioglass-free samples. Cell biological characterization using rat mesenchymal stem cells (rMSCs) revealed a stimulatory effect of NBG on rMSC differentiation. The addition of bioglass thus promotes GG mineralizability and, depending on bioglass type, antibacterial properties and rMSC differentiation.

High‐resolution synchrotronX‐ray analysis of bioglass‐enriched hydrogels

“…Bioglass A2 and S2 were produced by a sol–gel technique (see Table for composition). Self‐gelling GG–bioglass hydrogel composites (1% w/v bioglass, 0.7% w/v GG) were generated as described in previous work . Briefly, composite components were sterilized prior to composite fabrication by autoclaving (10 min, 115°C, 1.2 bars).…”

“…rMSC were derived from the bone marrow from of femora and tibiae of Lewis rats was performed as described by Lamers et al and in a previous publication . Briefly, bone marrow was expelled and disaggregated.…”

“…Addition of bioglass particles to a variety of noninjectable hydrogels resulted in enhanced apatite formation after incubation in SBF . Furthermore, addition of bioglass particles to the anionic, calcium‐binding polysaccharide gellan gum (GG), which has been investigated as a material for regeneration of skin, cartilage, and invertebral discs, can promote GG hydrogel formation and increase compressive strength . This is presumably due to the release of such ions as Ca 2+ from bioglass particles, which ionically cross‐link the anionic GG polymer chains.…”

Injectable hydrogels for cartilage and bone tissue engineering

“…Other inorganic materials such as nanosilica and Bioglass have been studied for the preparation of hybrid hydrogel systems. 288,289 For example, Vishnu Priya et al 290 have developed an injectable hydrogel system by using chitin and poly(butylene succinate) loaded with fibrin nanoparticles and magnesium-doped Bioglass. This hydrogel system enhances the initiation of differentiation and expression of alkaline phosphatase and osteocalcin, thus indicating its promise for regenerating irregular bone defects.…”

Tissue engineering with gellan gum

“…Douglas et al mineralised GG scaffolds using the alkaline phosphatase enzyme to improve strength and stiffness of the material, as well as promote cell attachment and differentiation 35,77 . Douglas and others have also explored incorporating bioglass into GG hydrogels to improve mineralisation, bone regeneration and antibacterial properties 78,79 . Jamshidi et al achieved similar effects through the direct blending of GG with nanocrystalline hydroxyapatite 80 , whilst Veira enhanced biomineralisation using gold nanorods that had been surface-functionalised with GG 81 .…”