An Injectable Polymer Gel Loaded with Periplaneta americana Extracts-Derived Microspheres for Drug Sustained Release and Chondrocyte Proliferation Promotion

In this study, a dual sustained-release injectable gel loaded with Periplaneta americana ( P. americana ) protein–polysaccharide complex (PPc) microspheres was developed to achieve prolonged protein release and promote chondrocyte proliferation. The system was constructed by encapsulating PPc-loaded microspheres within a cationic guar gum gel matrix. PPc extracted from P. americana residues were fabricated into microspheres via ionic emulsification cross-linking followed by glutaraldehyde fixation. The cationic guar gum gel incorporating these PPc microspheres was subsequently prepared through sequential acid–base neutralization, exhibiting favorable injectability, rheological behavior, and self-healing capacity. The optimized formulation (MS-6-gel) demonstrated excellent encapsulation efficiency and enabled sustained release of P. americana PPc, with a maximum cumulative release rate of 73.4%, indicating its potential for controlled and efficient local delivery. Kinetic analysis using Korsmeyer–Peppas and Weibull models revealed that the dual-barrier structure of the microsphere-in-gel system substantially retarded protein diffusion, thereby extending the release duration. Furthermore, MS-6-gel functioned as a multifunctional platform, not only exhibiting remarkable coagulation ability and potent antibacterial activity against both Staphylococcus aureus (100.0 ± 1.8%) and Escherichia coli (85.8 ± 2.8%), but also effectively supporting ATDC5 chondrocyte proliferation. In summary, this dual sustained-release gel system (MS-6-gel) integrates prolonged protein delivery, chondrocyte proliferation promotion, antibacterial, and hemostatic functions. Its unique microsphere-in-gel architecture enables controlled release kinetics, highlighting a promising nature-derived strategy for cartilage tissue engineering and biomedical applications.