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Methacrylated gelatin/hyaluronan-based hydrogels for soft tissue engineering.

ABSTRACT: In vitro-generated soft tissue could provide alternate therapies for soft tissue defects. The aim of this study was to evaluate methacrylated gelatin/hyaluronan as scaffolds for soft tissue engineering and their interaction with human adipose-derived stem cells (hASCs). ASCs were incorporated into methacrylated gelatin/hyaluronan hydrogels. The gels were photocrosslinked with a lithium phenyl-2,4,6-trimethylbenzoylphosphinate photoinitiator and analyzed for cell viability and adipogenic differentiation of ASCs over a period of 30?days. Additionally, an angiogenesis assay was performed to assess their angiogenic potential. After 24?h, ASCs showed increased viability on composite hydrogels. These results were consistent over 21?days of culture. By induction of adipogenic differentiation, the mature adipocytes were observed after 7?days of culture, their number significantly increased until day 28 as well as expression of fatty acid binding protein 4 and adiponectin. Our scaffolds are promising as building blocks for adipose tissue engineering and allowed long viability, proliferation, and differentiation of ASCs.

SUBMITTER: Kessler L

PROVIDER: S-EPMC5753891 | biostudies-other | 2017 Jan-Dec

REPOSITORIES: biostudies-other

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Methacrylated gelatin/hyaluronan-based hydrogels for soft tissue engineering.

Kessler Lukas L Gehrke Sandra S Winnefeld Marc M Huber Birgit B Hoch Eva E Walter Torsten T Wyrwa Ralf R Schnabelrauch Matthias M Schmidt Malte M Kückelhaus Maximilian M Lehnhardt Marcus M Hirsch Tobias T Jacobsen Frank F

Journal of tissue engineering 20170101

In vitro-generated soft tissue could provide alternate therapies for soft tissue defects. The aim of this study was to evaluate methacrylated gelatin/hyaluronan as scaffolds for soft tissue engineering and their interaction with human adipose-derived stem cells (hASCs). ASCs were incorporated into methacrylated gelatin/hyaluronan hydrogels. The gels were photocrosslinked with a lithium phenyl-2,4,6-trimethylbenzoylphosphinate photoinitiator and analyzed for cell viability and adipogenic differen ...[more]

PMID: 29318000

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Project description:BackgroundTissue engineering, which involves the selection of scaffold materials, presents a new therapeutic strategy for damaged tissues or organs. Scaffold design based on blends of proteins and polysaccharides, as mimicry of the native extracellular matrix, has recently become a valuable strategy for tissue engineering.ObjectiveThis study aimed to construct composite hydrogels based on natural polymers for tissue engineering.MethodsComposite hydrogels based on blends of gelatin with a polysaccharide component (chitosan or alginate) were produced and subsequently enzyme crosslinked. The other three hydrogels, chitosan hydrogel, sodium alginate hydrogel, and microbial transglutaminase-crosslinked gelatin (mTG/GA) hydrogel were also prepared. All hydrogels were evaluated for in vitro degradation property, swelling capacity, and mechanical property. Rat adipose-derived stromal stem cells (ADSCs) were isolated and seeded on (or embedded into) the above-mentioned hydrogels. The morphological features of ADSCs were observed and recorded. The effects of the hydrogels on ADSC survival and adhesion were investigated by immunofluorescence staining. Cell proliferation was tested by thiazolyl blue tetrazolium bromide (MTT) assay.ResultsCell viability assay results showed that the five hydrogels are not cytotoxic. The mTG/GA and its composite hydrogels showed higher compressive moduli than the single-component chitosan and alginate hydrogels. MTT assay results showed that ADSCs proliferated better on the composite hydrogels than on the chitosan and alginate hydrogels. Light microscope observation and cell cytoskeleton staining showed that hydrogel strength had obvious effects on cell growth and adhesion. The ADSCs seeded on chitosan and alginate hydrogels plunged into the hydrogels and could not stretch out due to the low strength of the hydrogel, whereas cells seeded on composite hydrogels with higher elastic modulus, could spread out, and grew in size.ConclusionThe gelatin-polysaccharide composite hydrogels could serve as attractive biomaterials for tissue engineering due to their easy preparation and favorable biophysical properties.

Project description:The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. Herein, we demonstrate for the first time an electrofluidic approach to controlled delivery into soft tissue models based on gelatin methacryloyl (GelMA) hydrogels. This was achieved using a surgical suture, whereby transport of bioactive molecules, including drugs and proteins, was controlled by imposition of an electric field. Commonly employed surgical sutures or acrylic threads were integrated through the hydrogels to facilitate the directed introduction of bioactive species. The platform consisted of two reservoirs into which the ends of the thread were immersed. The anode and cathode were placed separately into each reservoir. The thread was taken from one reservoir to the other through the gel. When current was applied, biomolecules loaded onto the thread were directed into the gel. Under the same conditions, the rate of movement of the biomolecules along GelMA was dependent on the magnitude of the current. Using 5% GelMA and a current of 100?µA, 2 uL of fluorescein travelled through the hydrogel at a constant velocity of 7.17?±?0.50 um/s and took less than 8?minutes to exit on the thread. Small molecules such as riboflavin migrated faster (5.99?±?0.40 ?m/s) than larger molecules such as dextran (2.26?±?0.55 ?m/s with 4?kDa) or BSA (0.33?±?0.07 ?m/s with 66.5?kDa). A number of commercial surgical sutures were tested and found to accommodate the controlled movement of biomolecules. Polyester, polyglactin 910, glycolide/lactide copolymer and polyglycolic acid braided sutures created adequate fluid connection between the electrodes and the hydrogel. With a view to application in skin inflammatory diseases and wound treatment, wound healing, slow and controlled delivery of dexamethasone 21-phosphate disodium salt (DSP), an anti-inflammatory prodrug, was achieved using medical surgicryl PGA absorbable suture. After 2?hours of electrical stimulation, still 81.1% of the drug loaded was encapsulated within the hydrogel.

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Methacrylated gelatin/hyaluronan-based hydrogels for soft tissue engineering.

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Methacrylated gelatin/hyaluronan-based hydrogels for soft tissue engineering.

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