4.7 Article

Novel hyaluronic acid-tyrosine/collagen-based injectable hydrogels as soft filler for tissue engineering

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 141, Issue -, Pages 700-712

Publisher

ELSEVIER
DOI: 10.1016/j.ijbiomac.2019.08.233

Keywords

Hydrogels; Hyaluronic acid-tyrosine; Human-like collagen; Soft tissue filling; Biocompatibility

Funding

  1. National Natural Science Foundation of China [21838009, 21606179, 21576223, 21576160]
  2. Shaanxi Key Laboratory of Degradable Biomedical Materials Program [15JS105]

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In this study, we fabricated multifunctionalized hydrogel scaffolds based on hyaluronic acid (HA)-tyrosine and human-like collagen (HLC) by crosslinking with 1, 4-butanedioldiglycidyl ether (BDDE) for soft tissue fillers. The physicochemical of HA-tyrosine/BDDE (HTB) and various proportions of HA-tyrosine/BDDE/HLC (HTBH) hydrogels were characterized by swelling ratio, mechanical strength, morphology and thermal stability. The results demonstrated various HTBH hydrogels had superior performance in mechanical properties than HTB hydrogels. The biodegradation in vitro results demonstrated the degradation of HTBH hydrogels were slower than HTB hydrogels, and residual masses of HTBH hydrogels varied with different proportions of HA-tyrosine and HLC in the presence of the combination of HAse/collagenase I. The cell counting kit-8 (CCK-8), Hoechst/PI staining and cell adhesion of various HTBH hydrogels showed less cytotoxic and superior fibroblast attachment than those of HTB hydrogels. Moreover, subcutaneous injections of HTBH hydrogels containing high proportions of HLC in mice and rabbits all exhibit better biocompatibility and anti-biodegradation compared to HTB hydrogels after 1, 4, 8, 12 and 16 weeks. Hematoxylin-eosin staining (H&E), immunohistochemical and transmission electron microscope (TEM) analysis results indicated HTBH hydrogels had less intense inflammatory responses with increase proportion of HLC. Taken together, HTBH hydrogels had great potential application as ideal soft tissue fillers with excellent mechanical properties, biological stability and biocompatibility. (C) 2019 Elsevier B.V. All rights reserved.

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