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Sustained low-dose dexamethasone delivery via a PLGA microsphere-embedded agarose implant for enhanced osteochondral repair
- Source :
- Acta Biomater
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Articular cartilage defects are a common source of joint pain and dysfunction. We hypothesized that sustained low-dose dexamethasone (DEX) delivery via an acellular osteochondral implant would have a dual pro-anabolic and anti-catabolic effect, both supporting the functional integrity of adjacent graft and host tissue while also attenuating inflammation caused by iatrogenic injury. An acellular agarose hydrogel carrier with embedded DEX-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres (DLMS) was developed to provide sustained release for at least 99 days. The DLMS implant was first evaluated in an in vitro pro-inflammatory model of cartilage degradation. The implant was chondroprotective, as indicated by maintenance of Young's modulus (EY) (p = 0.92) and GAG content (p = 1.0) in the presence of interleukin-1β insult. In a subsequent preliminary in vivo experiment, an osteochondral autograft transfer was performed using a pre-clinical canine model. DLMS implants were press-fit into the autograft donor site and compared to intra-articular DEX injection (INJ) or no DEX (CTL). Functional scores for DLMS animals returned to baseline (p = 0.39), whereas CTL and INJ remained significantly worse at 6 months (p Statement of significance Articular cartilage defects are a common source of joint pain and dysfunction. Effective treatment of these injuries may prevent the progression of osteoarthritis and reduce the need for total joint replacement. Dexamethasone, a potent glucocorticoid with concomitant anti-catabolic and pro-anabolic effects on cartilage, may serve as an adjuvant for a variety of repair strategies. Utilizing a dexamethasone-loaded osteochondral implant with controlled release characteristics, we demonstrated in vitro chondroprotection in the presence of IL-1-induced degradation and improved in vivo functional outcomes following osteochondral repair. These improved outcomes were correlated with superior histological cartilage scores and minimal-to-no comorbidity, which is a risk with high dose dexamethasone injections. Using this model of cartilage restoration, we have for the first time shown the application of targeted, low-dose dexamethasone for improved healing in a preclinical model of focal defect repair.
- Subjects :
- Cartilage, Articular
medicine.medical_specialty
0206 medical engineering
Anti-Inflammatory Agents
Biomedical Engineering
Urology
02 engineering and technology
Osteoarthritis
Biochemistry
Dexamethasone
Article
Biomaterials
chemistry.chemical_compound
Dogs
Polylactic Acid-Polyglycolic Acid Copolymer
In vivo
medicine
Animals
Autografts
Molecular Biology
Drug Carriers
Bone Transplantation
business.industry
Sepharose
Cartilage
General Medicine
021001 nanoscience & nanotechnology
medicine.disease
020601 biomedical engineering
Controlled release
Microspheres
Hindlimb
PLGA
medicine.anatomical_structure
chemistry
Delayed-Action Preparations
Joint pain
Cattle
Implant
medicine.symptom
0210 nano-technology
business
Biotechnology
medicine.drug
Subjects
Details
- ISSN :
- 17427061
- Volume :
- 102
- Database :
- OpenAIRE
- Journal :
- Acta Biomaterialia
- Accession number :
- edsair.doi.dedup.....d02a01b9ce79f5f2d46317655febc636