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[1-3]
in personalized healthcare, precision medicine, and human-machine interfaces . However, different from
inherently soft human tissues, conventional wearable devices are usually made with rigid materials, causing
[4]
unstable integration with tissues and discomfort . Polymer gels, composed of three-dimensional polymer
networks and dispersion media, have brought many opportunities to wearable sensors by harnessing their
mechanical flexibility, structural permeability, and tissue resemblance . However, general synthetic
[5,6]
polymer gels have poor biocompatibility and non-degradability, leading to severe immune response and a
serious threat to environmental sustainability .
[7]

Biogels derived from natural biopolymers (such as alginate, cellulose, and gelatin) are gaining research
interest as building blocks for wearable sensors, ascribing to their biocompatibility and environmental
sustainability [8-11] . The biogels’ biocompatibility enables long-term skin contact without irritation or
inflammation, while their environmental degradability presents a sustainable approach to mitigating
electronic waste. Gelatin, as a hydrolyzed product of natural collagen, is a type of protein composed of
polypeptides. Collagen is generally water-insoluble, composed of three long helix-shaped chains of amino
acids [Figure 1A] . Compared to collagen, gelatin is a mixture of single- and multi-chain polypeptides
[12]
composed of amino acids such as alanine, proline, and 4-hydroxyproline with good water solubility. The
unique advantages of gelatin, including excellent biocompatibility, non-immunogenicity, biodegradability,
and multiple reactive sites for functionalization, make it a promising candidate for constructing soft biogels
as wearable sensors [Figure 1B] [13,14] . Although gelatin-based hydrogels can be formed by cooling a hot
gelatin solution to convert partial gelatin chains from random coil structures to triple-helix configuration,
the obtained hydrogel is fragile with low toughness, which makes it difficult to apply in flexible sensing
devices [12,15] .

DESIGN OF TOUGH GELATIN-BASED BIOGELS FOR WEARABLE SENSING DEVICES
A general design principle for tough gels is the incorporation of energy dissipation domains within
stretchable polymer networks . The molecular engineering and structural engineering, including
[16]
molecular interactions and topological network structures, are proposed to fabricate robust gels with high
[17]
stretchability, mechanical strength, and toughness . By manipulating functional groups at the molecular
level, diverse crosslinking interactions (including permanent or reversible dynamic bonds) can be
engineered within the polymer network for energy dissipation. Structural engineering mainly involves
introducing high-order structure (such as phase separation and hierarchical structure) into polymer
networks for strengthening and toughening gels. Various combinations of these effective strategies have
[18]
been explored for designing tough gelatin-based biogels . Considering the abundant functional groups in
gelatin chains, an effective strategy for toughening gelatin biogels is to regulate non-covalent associations
between gelatin chains [19-21] . For example, hydrophobic interaction domains and microphase separation
regions were introduced into the gelatin network through the Hofmeister effect by soaking virgin gelatin gel
in a (NH ) SO solution [Figure 1C] . The resulting gelatin hydrogels could withstand large tensile and
[19]
4 2
4
compressive forces with tensile strength of ca. 3 MPa when stretching to 500% [Figure 1D]. Besides,
introducing crosslinkers such as tannic acid (TA), sodium citrate, and sodium phytate to build non-covalent
crosslinks with gelatin chains is another effective way to enhance the mechanical properties of gelatin-based
biogels [22-25] . For example, Qin et al. reported a gelatin supramolecular organohydrogel by immersing a
gelatin pre-hydrogel in citrate (Cit) water-glycerol mixture solution [Figure 1E] . Due to the formation of
[22]
hydrophobic aggregation, ionic interactions between the -NH of gelatin and Cit anions, the
+
3-
3
organohydrogel exhibited high strength and toughness [Figure 1F]. Additionally, chemical modifications of
gelatin chains with crosslinkable groups (such as methacrylate and dopamine) have also been investigated to
create dually crosslinked structures for improving the mechanical properties of gelatin-based biogels [26,27] .
With significant advances in mechanical enhancement, compared with the synthetic polymer gels (such as