• • Physical entrapment of nanovesicles in hydrogels results in burst release profiles, with >60% cargo lost within 24 hours, whereas chemical crosslinking (covalent or supramolecular) reduces release rate to <20% over 7 days, enabling sustained delivery for chronic diseases.
• • Covalent conjugation of vesicles to polymer networks increases compressive modulus from 0.05 MPa (physical blend) to 1.2 MPa (crosslinked), a 24-fold enhancement that meets load-bearing requirements for cartilage tissue engineering.
• • Supramolecular crosslinking via host-guest interactions yields shear-thinning and self-healing hydrogels with recovery efficiency >90% after 5 cycles, critical for injectable formulations that withstand physiological shear forces (10–100 s⁻¹).
• • Hybrid hydrogels functionalized with cell-derived nanovesicles achieve >80% cell viability in vitro and reduce inflammatory cytokine TNF-α by 70% in vivo compared to bare hydrogels, demonstrating immunomodulatory potential for wound healing.