Vol. 7, Issue 2, Part B (2025)

Background: Conventional drug delivery systems suffer from common problems such as insufficient targeting, poor biocompatibility and uncontrolled release behavior.
Objective: To construct biomimetic hydrogels that can mimic the microenvironment of natural tissues and possess high loading and multiple response capabilities for precise and safe drug delivery.
Methods: Natural macromolecules such as collagen, hyaluronic acid and chitosan were used as the substrates, and the three-dimensional network was constructed by chemical crosslinking or physical cross-linking of calcium ions. After the introduction of pH/temperature/enzyme-responsive groups and targeting ligands, the in vivo distribution, controlled-release kinetics and therapeutic efficacy of hydrogels were systematically evaluated in tumor-bearing mice, type I diabetic rats and a model of whole-layer skin defects.
Results: The resulting hydrogel contained ≥15 wt% of drug; the 48-h cumulative release rate in the tumor microenvironment (pH 6.5, 37 °C, high MMP-2) was 82%, which was 3.4 times higher than that of the physiological conditions; the drug enrichment in the tumor site was elevated by 12.7-fold after tail vein injection, and tumor inhibition rate was 72%; the diabetic oral formulation was released by 70% in the intestines under the condition of pH 6.8 in 6 h, and the blood glucose fluctuation & lt;2mmolL-¹; wound application group healing time shortened by 40%, collagen arrangement more regular.
Conclusion: Bionic hydrogels are both biocompatible and environmentally responsive, which can significantly enhance the precision of drug targeting and release, and provide a feasible strategy for oncology, metabolic diseases, and tissue repair their scale-up and in vivo stability need to be further optimized in order to promote clinical translation.