SLR - January 2021 - Joseph H. Altepeter
Reference: Yan W, Xu X, Xu Q, Sun Z, Lv Z, Wu R, Yan W, Jiang Q, Shi D. An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study. Am J Sports Med. 2020 Nov 48(13):3233-3244. doi: 10.1177/0363546520957346. Epub 2020 Oct 7. PMID: 33026830.Level of Evidence: Level V (animal study, randomised controlled trial)
Scientific Literature Review
Reviewed By: Joseph H. Altepeter, DPM
Residency Program: Ascension St. Vincent - Indianapolis, IN
Podiatric Relevance: Osteochondral lesions can be a frustrating pathology to treat, and usually progress to surgical management. A common pathology of the tibiotalar joint, they are largely addressed arthroscopically with an array of techniques depending upon the size of the defect. Often, the adjunctive use of autograft, allograft, or bioengineered tissue is employed. A recent study demonstrated the potential benefit of m-hyaluronic acid hydrogel with kartogenin-loaded PLGA nanoparticles (m-HA+KGN) in a rabbit model. The current study sought to evaluate the same treatment in a large animal model to more closely mimic human application. The authors hypothesized primarily that m-eHA+KGN would facilitate hyaline cartilage and subchondral bone tissue repair; and secondarily that defect size/type would influence the efficacy of m-HA+KGN.
Methods: 48 mature minipigs were assigned to one of three groups: m-HA+KGN treatment, m-HA treatment, and blank treatment. Full-thickness chondral or osteochondral defects, 6.5mm or 8.5mm in diameter, were created in the medial femoral condyle weight-bearing region of bilateral knees and treated according to group. They were allowed to move freely until sacrificed and assessed at either 6 or 12 months postoperatively, when MRI, micro-CT (m-CT), histological, immunohistochemical, biomechanical, and photographic assessments were performed. The International Cartilage Repair Society (ICRS) macroscopic score, ICRS histological score, and Whole-Organ Magnetic Resonance Imaging Score (WORMS) values were analyzed using a Kruskal-Wallis test with 95% CI. The m-CT quantitative analysis and biomechanical testing were analyzed with the Bonferroni multiple comparison test. A general linear model evaluated the influence of defect size/type on therapeutic efficacy of m-HA+KGN.
Results: There was superior gross and histological healing in the m-HA+KGN group at 6 and 12 months. Macroscopically, the m-HA+KGN group demonstrated smoother cartilage surfaces without signs of arthritic changes. The m-HA+KGN group showed more hyaline-like cartilage, exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen, with greater integration of m-HA+KGN with surrounding native tissue. The biomechanical properties were also improved after m-HA+KGN treatment, while 6.5mm defects and full-thickness chondral defects showed significantly higher ICRS macroscopic and histological scores compared with 8.5mm or osteochondral defects. Improved quality of the repaired cartilage was demonstrated by MRI, along with lower WORMS values, for the m-HA+KGN group; and better subchondral bone reconstruction was observed on m-CT. In every analysis, defect size significantly influenced the therapeutic efficacy of m-HA+KGN, favoring the smaller/shallower defects.
Conclusions: The authors concluded that the use of m-HA+KGN for treating chondral lesions has the potential to be an effective modality by creating superior biomechanical and histological cartilage repair. The study is obviously limited as an animal study, and did not allow for comparison with other methods of addressing this type of lesion. This appears to be a promising option at this point of the testing process, it will be interesting to see how this method evolves and compares going forward before potentially becoming an option in human medicine.