Tough Injectable Hydrogels by Combining Elastic and Energy Dissipation

Hydrogels closely resemble living tissues, featuring a classical three-dimensional (3D) network structure composed of a hydrophilic polymer network and surrounding water-based fillers. This bionic resemblance has led to the development of hydrogels for numerous biomedical applications. Among these, injectable hydrogel systems have attracted significant attention due to their ease of operation, efficient encapsulation viability, minimal invasiveness, and enhanced patient compliance. However, injectable hydrogels have long been considered mechanically weak and challenging to meet the requirements of biological applications under load-bearing conditions. The objective of this study is to develop tough injectable hydrogel systems without compromising their biocompatibility. Chapter One introduces the raw materials and in situ crosslinking methods for injectable hydrogels, and the universal hydrogel toughening design including elastic maintenance and mechanical energy dissipation. It also proposes combining mechanisms and guides the design of hydrogels with improved mechanical properties through biomimetic structuring and multi-scale collaboration, for diverse clinical applications. Chapter Two presents a single network (SN) injectable hydrogel with enhanced toughness, featuring a rigid and homogeneous hyaluronic acid (HA) framework linked by polyethylene glycol (PEG) flexible long chains. This structure design increases compressive stress by 7 times and toughness by 4 times compared to conventional SN hydrogels. Chapter Three presents a thermo-entangled injectable hydrogel with high toughness, formed by self-assembly of diacrylated F127 (F127-DA) and crosslinked with HA framework via Thiol-ene Michael addition. It achieves a compressive strength of 9.08 MPa and toughness of 753 kJ/m³. Chapter Four investigates an acid-triggered double network (DN) injectable hydrogel. The first HA network forms via Thiol-ene Michael addition, while the second sodium alginate (SA) network is crosslinked by Ca2+ from acid-dissolvable hydroxyapatite (HAp) nanoparticles. This results in a 3-fold increase in compressive strength and 2.5-fold increase in toughness compared to normal DN hydrogels, with improved resistance to fatigue, swelling, and degradation. Chapter Five summarises the research findings and discusses future directions for the development of tough injectable hydrogels.