Bio-inspired hydrogel composed of hyaluronic acid and alginate as a potential bioink for 3D bioprinting of articular cartilage engineering constructs

Cristina Antich; Juan de Vicente; Gema Jiménez; Carlos Chocarro; Esmeralda Carrillo; Elvira Montañez; Patricia Gálvez-Martín; Juan Antonio Marchal

doi:10.1016/j.actbio.2020.01.046

Bio-inspired hydrogel composed of hyaluronic acid and alginate as a potential bioink for 3D bioprinting of articular cartilage engineering constructs

Acta Biomater. 2020 Apr 1:106:114-123. doi: 10.1016/j.actbio.2020.01.046. Epub 2020 Feb 3.

Authors

Cristina Antich¹, Juan de Vicente², Gema Jiménez³, Carlos Chocarro⁴, Esmeralda Carrillo¹, Elvira Montañez⁵, Patricia Gálvez-Martín⁶, Juan Antonio Marchal⁷

Affiliations

¹ Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18100, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada-University of Granada, 18100 Granada, Spain; Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada E-18012, Spain; Excellence Research Unit "Modeling Nature" (MNat), University of Granada, Spain.
² Excellence Research Unit "Modeling Nature" (MNat), University of Granada, Spain; Biocolloid and Fluid Physics Group, Department of Applied Physics, Faculty of Sciences, University of Granada, C/Fuentenueva s/n, 18071 - Granada, Spain.
³ Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18100, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada-University of Granada, 18100 Granada, Spain; Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada E-18012, Spain.
⁴ Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18100, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada-University of Granada, 18100 Granada, Spain; Excellence Research Unit "Modeling Nature" (MNat), University of Granada, Spain.
⁵ Department of Orthopedic Surgery and Traumatology, Virgen de la Victoria University Hospital, 29010 Málaga, Spain.
⁶ Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Granada, Granada E-18071, Spain; Advanced Therapies Area, Bioibérica S.A.U., Barcelona E-08029, Spain. Electronic address: galmafarma@gmail.com.
⁷ Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18100, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada-University of Granada, 18100 Granada, Spain; Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada E-18012, Spain; Excellence Research Unit "Modeling Nature" (MNat), University of Granada, Spain. Electronic address: jmarchal@ugr.es.

PMID: 32027992
DOI: 10.1016/j.actbio.2020.01.046

Abstract

Bioprinting is a promising tool to fabricate well-organized cell-laden constructs for repair and regeneration of articular cartilage. The selection of a suitable bioink, in terms of composition and mechanical properties, is crucial for the development of viable cartilage substitutes. In this study, we focused on the use of one of the main cartilage components, hyaluronic acid (HA), to design and formulate a new bioink for cartilage tissue 3D bioprinting. Major characteristics required for this application such as printability, biocompatibility, and biodegradability were analyzed. To produce cartilage constructs with optimal mechanical properties, HA-based bioink was co-printed with polylactic acid (PLA). HA-based bioink was found to improve cell functionality by an increase in the expression of chondrogenic gene markers and specific matrix deposition and, therefore, tissue formation. These results indicate that it is a promising bioink candidate for cartilage tissue engineering based in 3D bioprinting. STATEMENT OF SIGNIFICANCE: The recent appearance of 3D printing technology has enabled great advances in the treatment of osteochondral disorders by fabrication of cartilage tissue constructs that restore and/or regenerate damaged tissue. In this attempt, the selection of a suitable biomaterial, in terms of composition and mechanical properties, is crucial. In this study, we describe for first time the development of a bioink based on the main component of cartilage, HA, with suitable biological and mechanical properties, without involving toxic procedure, and its application in cartilage tissue bioprinting. Hybrid constructs prepared by co-printing this bioink and thermoplastic polymer PLA provided an optimal niche for chondrocyte growth and maintenance as well as mechanical properties necessary to support load forces exerted in native tissue. We highlight the translation potential of this HA-based bioink in the clinical arena.

Keywords: Bioink; Bioprinting; Cartilage tissue engineering; Hyaluronic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Absorbable Implants*
Alginates / chemistry
Bioprinting*
Cartilage, Articular / cytology
Cell Proliferation / drug effects
Cell Survival / drug effects
Chondrocytes / metabolism
Humans
Hyaluronic Acid / chemistry
Hydrogels / chemistry*
Ink
Printing, Three-Dimensional*
Tissue Engineering / methods*
Tissue Scaffolds / chemistry*
Viscosity

Substances

Alginates
Hydrogels
Hyaluronic Acid