Hyaluronic acid-loaded drug-eluting nanofibrous pad for the treatment of degenerative arthritis

Abstract

Despite advancements in modern technology, treating degenerative arthritis remains a challenge. This study developed a degradable, hyaluronic acid-loaded, drug-eluting nanofibrous pad designed to provide extended pain relief and prevent infection at the knee joint. The mechanical performance of the biodegradable pads was assessed, and the pharmaceutical discharge kinetics were estimated using an in vitro elution method. Additionally, in vivo pharmaceutical release and efficacy were tested using a rabbit activity model. The experimental results suggest that the degradable pad exhibited strong mechanical properties. In vitro, the drug-eluting nanofibrous pad sustained the release of teicoplanin, ceftazidime, and ketorolac for 10, 24, and 30 days, respectively, and maintained high levels of connective tissue growth factor elution over a 30-day period. Moreover, animal testing demonstrated that the pad released significant amounts of antimicrobial and pain-relieving agents in a rabbit knee joint model for over 28 days. Rabbits implanted with the drug-eluting pads exhibited activity levels comparable to those that did not undergo surgery. These findings indicate that the hyaluronic acid-loaded, drug-eluting nanofibrous degradable pad, with its extended release of pharmaceuticals and biomolecules, may be used for the treatment of degenerative arthritis.

Fig. 1. (A) Layout and dimension of the mold for fabricating the pad, (B) photo of hyaluronic acid loaded pads. (unit: mm).

Fig. 2. The surgical procedure: (A) exposing the knee joint, (B) implanting the drug-eluting pad, and (C) closing the wound.

Fig. 3. The cage used to evaluate the animals' activities post-operation.

Fig. 4. Load-deformation curve of hyaluronic acid loaded PCL pads fabricated with different PCL/DCM ratios (either 2.5 g/4 mL or 2.5 g/7 mL).

Fig. 5. SEM images and fiber partice size distribution of electrospun (A) pure PLGA nanofibers, (B) drugs loaded nanofibers, (C) CTGF incorporated sheath-core nanofibers.

Fig. 6. Wetting angles of (A) virgin PLGA nanofibers, (B) drugs loaded nanofibers, (C) CTGF loaded nanofibers.

Fig. 7. (A) FTIR spectra, (B) DSC thermograms of virgin PLGA and drugs (ceftazidime, teicoplanin, and ketorolac) loaded PLGA nanofibers.

Fig. 8. In vitro (A) daily and (B) cumulative release of teicoplanin, ceftazidime, and ketorolac, as well as (C) daily discharge of CTGF from the nanofibers.

Fig. 9. In vivo elution of teicoplanin, ceftazidime, and ketorolac from the drug-eluting nanofibrous pads.

Fig. 10. Activity counts of animals (A) on various days, and (B) at different sensor locations (**, p < 0.01).

Fig. 11. Microscopic images of hematoxylin-and-eosin-stained tissue samples collected from the suprapatellar pouch of the knee joint at 1, 7, 14, and 28 days post-surgery (scale bar: 500 μm).