Table 2:

Summary of peptide-based hydrogels that use affinity-based interactions to reversibly bind and release their cargo

Affinity-Based Interaction	Peptide Gel Matrix	Cargo delivered	Release Duration	Ref	Notes
Electrostatic: Specific	α–helical peptide amphiphile + Heparin = β sheet nanofiber	Growth factors: FGF-2-rhodamine	10 days	46
	Peptide-PEG conjugated gels + Heparin	Heparin binding proteins	~ 10 days	48
Electrostatic: Non-specific	Heparin-mimetic peptide amphiphile	Growth factors: VEGF	7 days	49
	β hairpin: HLT2 (cationic)	Proteins: α-lactalbumin, lactoferrin, myoglobin	28 days	58
	β hairpin: VEQ3 (anionic)	Proteins: α-lactalbumin, lactoferrin, myoglobin	28 days	58
	β sheet: RADA16	Growth factors: β-FGF, VEGF, BDNF	> 2 days	63
	β hairpin: STINGel MDP - K2(SL)6K2	Cyclic dinucleotide (CDN)	> 24 hours	64
	β hairpin: SLac MDP- (KSLSLSLRGSLSLSLKGRGDS)	Small molecule drugs: suramin	> 30 days	66
	β hairpin: AcVES3	Proteins: EGFP; Cytokines: IFNα	10 days	60	Cargo modified with affinity tags
Hydrophobic	β hairpin: MDP - K2(SL)3(SA)(SL)2K2	Small molecule drugs: SN-38, Diflunisal, Etodolac	> 8 days	67,68
	Single amino acid hydrogel nanoparticles (HNPs)	Small molecule drugs: 5-fluorouracil	t1/2 = 3–9 hrs	60
	MITCH gel	QK (VEGF-mimetic peptide)	> 21 days	70	Cargo modified with affinity tags
Combination Systems: Electrostatic & Hydrophobic	Phe-modified RADA	Small molecule drugs: 5-fluorouracil	n/a	72
	Hexapeptide: NH2-WLVFFK-COOH	Small molecule drugs: 5-fluorouracil, ciprofloxacin	72 hrs	73
	Composite RADA gel-chitosan system with β-Cyclodextrin carriers	Small molecule drugs: dexamethasone	~ 9 days (pH 7) > 9 days (pH 6)	74
Reversible Covalent: Schiff Base	Peptides with aldehyde functionality: Nap-GDFDFDpY-CHO	Small molecule drugs: Doxorubicin, Gemcitabine	> 12 hours	80,81
Reversible Covalent: Hydrazone	Peptide amphiphile modified with hydrazine	Small molecule drugs: nabumetone	> 24 days	82