Hyaluronic acid and dextran hydrogels for tissue engineering applications
Alma Banigo is a PhD student in the Department Developmental BioEngineering. (Co)Promotors are prof.dr. H.B.J. Karperien and dr. B. Zoetebier from the Faculty of Science & Technology.
Hydrogels have emerged as an important tool in tissue engineering for repairing and replacing of tissues, with hyaluronic acid-based hydrogels becoming a promising type as well as dextran in this field. While research findings are optimistic and encouraging, especially within controlled laboratory environments, significant challenges persist in their application for bioprinting complex constructs, bioactivity as well as in using them as injectable solutions for addressing articular cartilage defects. Moreover, transitioning these laboratory successes to clinical settings faces hurdles due to the complexity of strategies involved or the need to explore lesser-known options. In this thesis, we concentrate on three key areas namely advanced 3D bioprinting, bioactivity studies and injectability to fill defects.
Coaxial and Triaxial Bioprinting (Review)
Chapter 2 delves into hydrogel-based bioinks for coaxial and triaxial bioprinting, providing a comprehensive review of their material characteristics, printing methodologies, and applications. This analysis highlights the potential of these bioinks to revolutionize bioprinting technology and their promising applications in tissue engineering and regenerative medicine.
Coaxial Bioprinting (Research)
Chapter 3 presents a novel one-step approach for coaxial bioprinting of both simple and complex structures. This method allows the simultaneous printing of bioink (cells and high molecular weight hyaluronic acid-tyramine [HMW HA-TA]), crosslinking agents, and sacrificial ink. Initial results show cell viability within core filaments, but additional research is necessary to improve cell proliferation and the production rate of these filaments. The goal is to advance the capability of coaxial bioprinting for creating complex tissues using hyaluronic acid-based hydrogels.
Injectability (Review)
Chapter 4 examines the role of injectable hydrogels in cartilage tissue engineering, focusing on material selection, crosslinking mechanisms, and production techniques. It highlights the importance of biocompatibility and mechanical properties for successful tissue regeneration.
The chapter also discusses current clinical trials and product developments, emphasizing future improvements in mechanical strength and host tissue integration.
Bioactivity study (Research)
Chapter 5 investigates the bioactivity of hyaluronic acid hydrogels of varying molecular weights (low, medium, and high) with added low concentrations of gelatin-tyramine (Gel-TA). Despite variations, the storage modulus remained stable, and cell viability was high across all hydrogels, with the softest hydrogels showing the highest viability. Different molecular weights affected degradation rates and cartilage matrix deposition. Future research will focus on optimizing hydrogel formulations for better mechanical properties and bioactivity, and exploring advanced crosslinking techniques for 3D bioprinting applications.
Injectability (Research)
Chapter 6 explores the application of injectable low molecular weight dextran-tyramine and medium molecular weight hyaluronic acid-tyramine (LMW Dex-TA/MMW HA-TA) in equine articular cartilage defects. While the hydrogels remained in place in cadaver studies, retention was an issue in live ponies. Further optimization is needed to enhance hydrogel viscosity and mechanical properties for better therapeutic efficacy.
Bioactivity study (Research)
Chapter 7 introduces a dual-functional hydrogel, combining maleimide (Mal) and tyramine (TA) groups on dextran. This allows for fast in situ crosslinking and targeted coupling of biomolecules. Despite a slight decline in cell viability over two weeks, the hydrogel maintained over 60% viability. Further optimization and incorporation of bioactive molecules could enhance the hydrogel’s versatility and functionality, making it a promising candidate for tissue engineering and regenerative medicine.
These Chapters collectively highlight the innovative strides in hydrogel-based bioinks, bioprinting techniques, and injectable hydrogels for tissue engineering. While significant progress has been made, ongoing research is essential to address remaining challenges and fully realize the potential of these technologies in clinical applications.
