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Peer-reviewedCC BYJournal of Functional Biomaterials

Hyaluronic Acid-Based Biomaterials in Tissue Engineering: From Molecular Properties to Re-Generative Applications

  • Chao-Ming Su1
  • Ming‐You Shie2,3
  • Wan-Ni Huang1
  • Fang-Jou Chiu4
  • Hong-Kai Chen1,4
  • Yi-Wen Chen1,5
  • Yu-Fang Shen4,6
6 affiliations
  1. 1Advanced Therapeutic & Pharmaceutical Center, China Medical University Hospital, Taichung City 40447, Taiwan
  2. 2School of Dentistry, China Medical University, Taichung City 40447, Taiwan
  3. 3Xenotransplantation Translational Research Center, China Medical University Hospital, Taichung City 40447, Taiwan
  4. 4Department of Bioinformatics and Medical Engineering, Asia University, Taichung City 41354, Taiwan
  5. 5Graduate Institute of Biomedical Sciences, China Medical University, Taichung City 40447, Taiwan
  6. 6High Performance Materials Institute for xD Printing, Asia University, Taichung City 41354, Taiwan
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Abstract

Hyaluronic acid (HA), a native non-sulfated glycosaminoglycan of the extracellular matrix, has emerged as a central biomaterial in tissue engineering due to its biocompatibility, hydration capacity, and receptor-mediated bioactivity. Beyond its structural role, HA actively regulates cellular behaviors through interactions with receptors such as CD44 and RHAMM, with outcomes highly dependent on molecular weight, degradation state, and matrix context. Recent advances in chemical modification and crosslinking strategies have enabled the development of HA-based hydrogels, nanofibers, and composite systems with tunable mechanics and degradation profiles, supporting applications in bone, cartilage, vascular, and skin regeneration, as well as in emerging platforms such as 3D bioprinting and nanomedicine. However, inconsistent biological responses and limited clinical translation remain key challenges. This review integrates current understanding of HA synthesis, physicochemical properties, degradation, and receptor-mediated signaling, and establishes a mechanistic framework linking molecular characteristics, matrix mechanics, and cell responses. Building on this framework, we outline design strategies for multifunctional HA composites, advanced biofabrication approaches, and receptor-targeted systems, providing a basis for the rational engineering of next-generation HA-based biomaterials with improved translational potential.

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Cite

BibTeXRIS
BibTeX
@article{su2026hyaluronic,
  title = {{Hyaluronic Acid-Based Biomaterials in Tissue Engineering: From Molecular Properties to Re-Generative Applications}},
  author = {Chao-Ming Su and Ming‐You Shie and Wan-Ni Huang and Fang-Jou Chiu and Hong-Kai Chen and Yi-Wen Chen and Yu-Fang Shen},
  journal = {Journal of Functional Biomaterials},
  year = {2026},
  month = may,
  doi = {10.3390/jfb17050246},
  url = {https://doi.org/10.3390/jfb17050246},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Hyaluronic Acid-Based Biomaterials in Tissue Engineering: From Molecular Properties to Re-Generative Applications
AU  - Chao-Ming Su
AU  - Ming‐You Shie
AU  - Wan-Ni Huang
AU  - Fang-Jou Chiu
AU  - Hong-Kai Chen
AU  - Yi-Wen Chen
AU  - Yu-Fang Shen
PY  - 2026
DA  - 2026/05/14
JO  - Journal of Functional Biomaterials
DO  - 10.3390/jfb17050246
UR  - https://doi.org/10.3390/jfb17050246
AB  - Hyaluronic acid (HA), a native non-sulfated glycosaminoglycan of the extracellular matrix, has emerged as a central biomaterial in tissue engineering due to its biocompatibility, hydration capacity, and receptor-mediated bioactivity. Beyond its structural role, HA actively regulates cellular behaviors through interactions with receptors such as CD44 and RHAMM, with outcomes highly dependent on molecular weight, degradation state, and matrix context. Recent advances in chemical modification and crosslinking strategies have enabled the development of HA-based hydrogels, nanofibers, and composite systems with tunable mechanics and degradation profiles, supporting applications in bone, cartilage, vascular, and skin regeneration, as well as in emerging platforms such as 3D bioprinting and nanomedicine. However, inconsistent biological responses and limited clinical translation remain key challenges. This review integrates current understanding of HA synthesis, physicochemical properties, degradation, and receptor-mediated signaling, and establishes a mechanistic framework linking molecular characteristics, matrix mechanics, and cell responses. Building on this framework, we outline design strategies for multifunctional HA composites, advanced biofabrication approaches, and receptor-targeted systems, providing a basis for the rational engineering of next-generation HA-based biomaterials with improved translational potential.
SN  - 2079-4983
ER  -