Injectable hydrogel filled into porous scaffolds combined with ultrasound-controlled drug release

Injectable hydrogels can form in situ at bone defect sites, serving as filling materials, drug delivery carriers, and cell growth scaffolds. However, their limited mechanical strength and uncontrollable drug release restrict their application in orthopedics. This study integrates injectable hydrogels into 3D-printed porous scaffolds to meet the biomechanical demands of orthopedic applications. Ultrasound was employed to modulate hydrogel drug release, enabling on-demand delivery.

Diclofenac sodium-loaded injectable hydrogel (Gel-DS) were incorporated into 3D-printed polylactic acid (PLA) porous scaffolds. The system was optimized via rheological and injectability tests; cell biocompatibility was assessed using CCK-8 assays. In vitro drug release under ultrasonic stimulation was analyzed, and in vivo therapeutic effect on arthritis rats was evaluated.

PLA porous scaffolds (1.00-mm spacing) offer high printing accuracy, adequate filling capacity, enhanced mechanical performance, and cytocompatibility. Ultrasound exposure showed negligible adverse effects on cellular activity. Porous structures increase specific surface area to regulate drug release kinetics. Ultrasound shifted the drug release mechanism from diffusion combined with erosion to erosion-dominated, increasing cumulative release at 8 h from 26.0% to 46.8%. In carrageenan-induced arthritic rats, Gel-DS combined with ultrasound treatment restored knee diameter to near-healthy levels (12.92 mm vs. 13.00 mm in the healthy group) and increased paw withdrawal threshold (26.0 g vs. 6.0 g in the untreated model group) demonstrating significant anti-edematous and analgesic effects.

The combination of injectable hydrogels with 3D-printed scaffolds demonstrates an effective strategy for bone defect repair, and integration with ultrasound enables long-term controlled and on-demand drug delivery.