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Recombinant fibroblast growth factor-18 (sprifermin) enhances microfracture-induced cartilage healing.

Abstract: Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated animals functional and structural outcomes over 24 weeks. For primary outcome measures, we performed histological evaluations and gene expression analysis of aggrecan, collagen types I and II, and cartilage oligomeric matrix protein in three regions of interest. As secondary outcome measures, we examined animals' lameness, performed arthroscopic, radiographic, and computed tomography (CT) scan imaging and gross morphology assessment. We detected the highest treatment benefit following 100 μg sprifermin treatment. The overall histological assessment showed an improvement in the kissing region, and the expression of constitutive genes showed a concentration-dependent enhancement, especially in the peri-lesion area. We detected a significant improvement in lameness scores, arthroscopic evaluations, radiography, and CT scans following sprifermin treatment when results from three dose-treatment groups were combined. Our results demonstrated, for the first time, an enhancement on microfracture outcomes following sprifermin treatment suggesting a cartilage regenerative role and a potential benefit of sprifermin treatment in early cartilage injuries.
Publication Date: 2021-05-12 PubMed ID: 33934397PubMed Central: PMC8560655DOI: 10.1002/jor.25063Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

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This research investigates the use of sprifermin, a growth factor, to improve microfracture treatment outcomes and promote cartilage healing in horses with post-traumatic osteoarthritis. The results show that sprifermin treatment can enhance healing and potentially benefit patients with early cartilage injuries.

Objective of the Research

  • The primary goal of the study was to evaluate the impact of intra-articular sprifermin, a recombinant fibroblast growth factor 18, on microfracture treatment of cartilage defects caused by osteoarthritis in horses.
  • Microfracture treatment is a common surgical intervention aiming at regenerating damaged cartilage tissue.

Research Methodology

  • To test the effects of sprifermin, cartilage defects were created in the fetlock joints of 18 horses, followed by microfracture treatment. The horses were then either treated with differing doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, as controls.
  • Over the 24 weeks following treatment, the animals’ functional and structural outcomes were evaluated including histological evaluations and gene expression analysis focusing on several compounds that are key indicators of cartilage health.
  • As well as exploring these primary outcome measures, the study also examined lameness in the animals and made use of arthroscopic, radiographic, and CT scan imaging.

Research Findings

  • Results demonstrated that the application of 100 μg sprifermin led to the highest treatment benefit.
  • Increased improvement was observed in histological assessments and gene expression analysis, particularly in the area surrounding the lesion.
  • Significant improvements were also seen in lameness scores and in the results of arthroscopic evaluations, radiographic, and CT scan imaging when the results from all sprifermin-treated groups were combined.

Conclusion and Implications of the Research

  • The research findings showed that sprifermin enhances the outcome of microfracture treatments, suggesting a potential role in cartilage regeneration.
  • The benefits of sprifermin treatment could extend to early cartilage injury cases, leading to improved healing and potentially preventing the progression of osteoarthritis in these patients.

Cite This Article

APA
Hendesi H, Stewart S, Gibison ML, Guehring H, Richardson DW, Dodge GR. (2021). Recombinant fibroblast growth factor-18 (sprifermin) enhances microfracture-induced cartilage healing. J Orthop Res, 40(3), 553-564. https://doi.org/10.1002/jor.25063

Publication

ISSN: 1554-527X
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 40
Issue: 3
Pages: 553-564

Researcher Affiliations

Hendesi, Honey
  • Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Stewart, Suzanne
  • Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
Gibison, Michelle L
  • Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
Guehring, Hans
  • Merck KGaA, Darmstadt, Germany.
Richardson, Dean W
  • Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
Dodge, George R
  • Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Translational Musculoskeletal Research Center, Corporal Michael J Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.

MeSH Terms

  • Animals
  • Cartilage, Articular / pathology
  • Fibroblast Growth Factors / metabolism
  • Fibroblast Growth Factors / pharmacology
  • Fibroblast Growth Factors / therapeutic use
  • Fractures, Stress / drug therapy
  • Horses
  • Lameness, Animal / drug therapy
  • Lameness, Animal / metabolism
  • Lameness, Animal / pathology

Grant Funding

  • P30 AR069619 / NIAMS NIH HHS
  • R01 AR071340 / NIAMS NIH HHS
  • I01 RX001321 / RRD VA
  • I01 RX001213 / RRD VA

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