Advances in hybrid hydrogel design for biomedical applications: innovations in drug delivery and tissue engineering for gynecological cancers

Abstract

Hybrid hydrogels have emerged as multifunctional biomaterials for targeted drug delivery and tissue engineering in gynecologic oncology. In this review, we summarize recent advances in the design of hybrid hydrogels that combine polymer networks with nanomaterials to achieve tunable stimuli-responsiveness, enhanced mechanical strength, and improved biocompatibility. For example, preclinical studies of folate-conjugated liposomal doxorubicin have demonstrated enhanced accumulation and antitumor efficacy in ovarian cancer models, while growth factor-loaded hydrogel scaffolds have supported endometrial repair in rodent models. We discuss strategies for optimizing drug loading, controlling spatiotemporal release profiles in response to tumor-specific cues (such as pH or enzyme activity), and customizing scaffold architecture for patient-specific regenerative needs. Implementation challenges-including efficient encapsulation of multiple cargos, precise control over degradation rates, and scale-up for clinical manufacturing-are critically examined. Finally, we outline future directions, including multifunctional platforms that integrate real-time monitoring with combined chemo-immunotherapy and approaches to address regulatory and translation hurdles. This evidence-based analysis highlights how hybrid hydrogels can advance precision therapy and regenerative medicine for gynecologic cancers while there is a need for further validation in clinical settings.

Keywords: Drug delivery; Gynecological cancers; Hybrid hydrogels; Tissue engineering.

Fig. 1

The interaction between nanomaterials and tumor cells. (a) Nanoparticle endocytosis and transcytosis modified by antigen–antibody conjugation. (b) Liposomes reach the cancerous area from blood vessels through the EPR effect. (c) Magnetic nanoparticles coated with chitosan carrying 5-Fluorouracil show passive targeting at cancer cells under an external magnetic field. (d) Therapeutic AuNPs are blocked by the BBB under normal conditions. After FUS exposure, the BBB is temporarily opened by microbubble inertial or stable cavitation, allowing AuNPs to pass through. BBB: Blood–Brain Barrier. EPR: Enhanced Permeability and Retention. FUS: Focused Ultrasound

Fig. 2

Illustration representing the preparation process of pH and temperature sensitive hydrogel

Fig. 3

Schematic of the peptide self-assembly process into nanofibers

Fig. 4

Schematic showing the formation process of GOD/hPB@gellan hydrogel made of Prussian blue nanoparticles precipitated into polysaccharide gellan matrix containing glucose oxidase (GOD)

Fig. 5

(a) The original model of dynamic reciprocity, representing the minimum required unit for tissue-specific functions, includes the nucleus (N), microtubules (MT), intermediate filaments (IF), microfilaments (MF), and collagen (C). (b) A more comprehensive view of dynamic reciprocity