A biopolymer hydrogel with amino-functionalized bioactive glass foraccelerated bone regeneration17 December 2021, by Thamarasee Jeewandara

Preparation and biomedical application ofhydrogels.CAG was fabricated by forming electrostaticinteraction between cationic NBG and anionic AG. BAGwas obtained by simply mixing AG and BG component.A rat cranial bone defect model was used to detect thebiocompatibility and osteogenic activity of hydrogels.Cells in CAG exhibited favorable cell spreading, whilethere was no obvious cell pseudopodium observed inBAG. Moreover, bone regeneration was also enhancedin CAG compared with BAG. micro–computedtomography (?CT). Credit: Science Advances,10.1126/sciadv.abj7857

Composite hydrogels can incorporate naturalpolymers and bioactive glass as promisingmaterials for bone regeneration. However, theapplications of such constructs are limited by poorcompatibility between organic and inorganicphases. In a new study now published in ScienceAdvances, Xinxin Ding, and a research team inmedicine, in Shanghai China, formed anelectrostatically reinforced hydrogel (abbreviatedCAG) with improved interfacial compatibility. Toaccomplish this, they introduced amino-functionalized bioactive glass to the alginate/gellangum matrix. When compared with bioactive glass,

the electrostatically reinforced hydrogel indicated amore uniform porous structure with a pore size of200 µm and an optimal compressive strength of 66kPa. Using the reinforced hydrogel, the teampromoted the phenotype transition of macrophagesand upregulated the osteogenic gene expression ofstem cells. They showed how new bone formationwas also accelerated in vivo with enhancedbiomineralization of the electrostatically reinforcedhydrogel, with biocompatibility ideally suited forbone regeneration.

Bone regeneration in the clinic

In this study, Ding et al. developed hybrid hydrogelsby establishing interfacial bonds between differentphases. Bone defects typically occur in patientswith severe trauma, osteitis and other bonedeformities that are increasingly costly to repair.Methods of efficient bone repair are still a challengefor clinicians, therefore advances in materialsscience have led to the development of newbiomaterials to enhance methods of boneregeneration. Researchers have developed naturalbiopolymer-based hydrogels with outstandingbiocompatibility and biodegradability. Among the various natural polymers, alginate and gellan gumexhibit potential for clinical applications, since theyare economically feasible and easily gelled usingcalcium ions. Hydrogels made of gellan gum canalso induce satisfactory osteogenesis with porousstructural similarity to natural bone tissue for cellattachment and osteogenic differentiation. Despiteexisting methods, the mechanical properties of purehydrogels are insufficient for bone defect repair invivo. Since it is complex to synthesize hybrids withcovalent interfacial bonds between differentphases, non-covalent crosslinks are a morepractical method for clinical applications.

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Structural analysis of synthesized hydrogels. (A) Schemeof the preparation of NBG and CAG. APTMS,(3-aminopropyl) trimethoxysilane. (B) High-resolution x-ray photoelectron spectroscopy spectra of N1s in NBGparticles. a.u., arbitrary units. (C) Zeta potential of AG,BG, and NBG. (D) Fourier transform infrared spectra ofAG, BAG, and CAG. (E) X-ray diffractometer patterns ofAG, BAG, and CAG. (F) Scanning electron microscopy(SEM) image of BG. (G) SEM image of synthesizedNBG. Credit: Science Advances, 10.1126/sciadv.abj7857

Developing a novel hybrid hydrogel

The team developed an electrostatically reinforcedhydrogel made of cationic amino-modified bioactiveglass (NBG) and anionic gellan gum (AG). Theyimproved the interfacial compatibility by forming electrostatic interactions between organic andinorganic phases. To improve the gelation networkof the hydrogels, Ding et al. used calcium ions forionic cross-linking. As a control, Ding et al.developed a type of bioactive glass (BAG) bymixing nonfunctionalized bioactive glass (BG) andgellan gum (AG). The researchers aimed to createa self-assembled gelation network of hydrogels withenhanced shear-thinning and self-healing ability.They aimed to form the hydrogels with electrostaticinteractions between the constituent composites,characterize the physicochemical properties ofhydrogels and investigate the bone regenerativecapacity of diverse hydrogels. The team preparedthe NBG (amino-modified bioactive glass) and CAG(electrostatically reinforced hydrogel) by physicallymixing the components, followed by X-ray

photoelectron spectroscopy and Zeta potential testto investigate electrostatic interactions in thehydrogels and identified grafted amino groups onNBG.

Cross-sectional images of different hydrogels using SEManalysis. (A to C) SEM images of AG, BAG, and CAG. (Dto F) Magnified images of AG, BAG, and CAG. Whitearrows in (E) and (F) indicate the BG and NBG particleson the hydrogel surface. Credit: Science Advances,10.1126/sciadv.abj7857

Analyzing the structure of hydrogels

Using representative Fourier transform infrared(FTIR) spectra, the team then analyzed the threetypes of materials. Using X-ray diffractometers,they understood and detected the potentialcrystalline phases in hydrogels. Ding et al. nextstudied the effect of particles on the hydrogelmicrostructure, and detected the morphologies ofbioactive glass (BG) and amino-modified (NBG)bioactive glass via scanning electron microscopy.The scientists credited the presence ofhomogenous NBG particles to the synthetic methodand subsequently analyzed the microstructuremorphology of hydrogels by detecting cross-sectional images using SEM, where the poroussurfaces of gellan gum (AG) were smooth.Meanwhile, incorporating inorganic particlessubstantially affected the structural morphology ofthe biomaterials. The team also noted the identicalthree-dimensional (3D) porous architecture of BAG(the novel type of bioactive glass control) and CAG(the electrostatically reinforced hydrogel).

Physicochemical properties of diverse

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hydrogels

Since hydrogels are known for their property ofswelling; one of the most important physicalcharacteristics of the material, swollen hydrogelspromoted the exchange of substances byabsorbing nutrients from the external environment.By incorporating bioactive glass in this work, Dinget al. significantly decreased the swelling ratio ofBAG (the novel bioactive glass) when comparedwith gellan gum. The fluid retention properties ofthe material allowed the infiltration of cells intoscaffolds, and facilitated efficient nutrient transportbetween the extracellular matrix and the hydrogel.Upon in vivo implantation, the encapsulated cellswere able to grow well in a nutrient richenvironment. However, since hydrogels typicallydegrade after implantation in the human body,where scaffolds can degrade at a rate comparablewith tissue regeneration. The scientists studied thedegradation behavior of hydrogels by detecting thechange in gel weight in time. The stabledegradation rate of the CAG (electrostaticallyreinforced hydrogel) biomaterial allowed itsretention in the osteogenic space for a long timeafter implantation with benefits for osteogenesis.The researchers additionally investigated themechanical properties of hydrogels via rheologyand compressive strength experiments.

Osteogenic differentiation of BMSCs cultured onhydrogels. (A) Confocal laser scanning microscopy

(CLSM) images of cells cultured for 24 hours [(a), control,(b) AG, (c) BAG, and (d) CAG]. (B) Cell Counting kit-8(CCK-8) assay of cells cultured for 1, 3, and 7 days. **P Immune response and osteogenic differentiation ofthe cells on the biomaterials in vitro

Materials scientists carefully monitor most newbone substitute materials for immune responses atthe defect site. Here, Ding et al. investigated thecell migration ability and inflammatory geneexpression to determine the immune response afterhydrogel treatment. Both BAG and CAGbiomaterials showed improved cell migration whencompared to other controls and indicated a successful induction of immune responses. To thenunderstand cell biocompatibility, the team satisfiedthe parameters of cell morphology and migration onhydrogels for early tissue regeneration. Toaccomplish this, they used rat bone marrow stemcells and cultured them on the biomaterials. TheCAG biomaterial assisted cell attachment andspreading, while amino groups on the NBG surfaceenabled protein adsorption for cell migration, whileBAG did not show suitability for cell adhesion.

Newly bone formation in a rat cranial bone defect model.(A) ?CT images of calvaria samples, (A, a to d) samplesfrom 2-week post-surgery group. (A, e to h) Samplesfrom 8-week post-surgery group. Images of (A) (a to h)exhibit the same scale bar of 1 mm. (B) Quantitativeanalysis of newly bone formation at 2 and 8 weeks.Notes: Bone volume/tissue volume (BV/TV), bonemarrow density (BMD), trabecular thickness (Tb.Th), andstructure model index (SMI). *P

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Outlook—bone forming potential of hydrogels in vivo

Given the enhanced osteogenic performance of CAG, theteam next investigated the material in a rat cranial defectmodel to detect bone regenerative capacity of hydrogelsin vivo. They noted an inflammatory response uponimplantation, which led to the recruitment of a largenumber of macrophages at the defect site. Ding et al.also noted the increased expression of bone marrowstem cells at the defect site, using immunohistochemistryand credited the enhanced recruitment of cells to themorphology of CAG, which contained relatively largerpores to facilitate cell recruitment and bone growth at thedefect site, in order to accelerate bone repair. Furtherstudies included micro-computed tomography methodsand histology staining, alongside sequential fluorescencelabeling to understand bone regeneration among diversebiomaterials. In this way, Xinxin Ding and colleaguesshowed how improved interfacial biocompatibilitybetween different phases contributed to the improvementof composite hydrogels. The diverse biomaterialsenhanced the capacity for bone regeneration andprovided a convenient approach to develop newcomposite hydrogels that can be translated for clinicalapplications.

More information: Xinxin Ding et al, A biopolymerhydrogel electrostatically reinforced by amino-functionalized bioactive glass for accelerated boneregeneration, Science Advances (2021). DOI:10.1126/sciadv.abj7857

Nathaniel Huebsch et al, Matrix elasticity of void-forminghydrogels controls transplanted-stem-cell-mediatedbone formation, Nature Materials (2015). DOI:10.1038/nmat4407

© 2021 Science X NetworkAPA citation: A biopolymer hydrogel with amino-functionalized bioactive glass for accelerated boneregeneration (2021, December 17) retrieved 8 June 2022 from https://phys.org/news/2021-12-biopolymer-hydrogel-amino-functionalized-bioactive-glass.html

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