Biopolymer-based intra-articular delivery of DKK1 into the contracted rabbit knee

Suenghwan Jo, Eric A. Lewallen, Luke B. Morrey, Scott M. Riester, William H. Trousdale, Christopher G. Salib, Nicolas Reina, Michael J. Yaszemski, Joaquin Sanchez-Sotelo, Mark E. Morrey, Andre J. van Wijnen, Matthew P. Abdel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Post-traumatic joint contractures reduce range of motion and require surgical intervention. Repeated surgical interventions can also cause recurrent contractures, leading to a paradox that highlights the need for alternative treatment strategies. Gene expression analysis by next generation sequencing of RNA (RNA-seq) from joint tissues revealed that Wnt ligands are actively expressed in joint capsules. Therefore, we investigated the intra-articular surgical implantation of an inhibitor of fibrotic cell differentiation as a possible strategy for treating post-traumatic joint contracture. Wnt/β-catenin signaling pathway inhibitor Dickkopf 1 (DKK1) was administered into rabbit knees using oligo[(poly(ethylene glycol) fumarate)] hydrogels (OPF). In vitro experiments were used to determine the cytotoxicity of DKK1 and appropriate dosing. Contractures were induced in skeletally mature female rabbits (n = 12) by disrupting knee joint capsules and immobilizing the joint by internal k-wire fixation. Surgical release was performed at 8 weeks when OPF containing DKK1 (or vehicle) was administered. In vitro results indicated that > 90% of DKK1 was released from OPF after 4 days, and rabbit fibroblasts remained viable at 200 nM (DKK1). Although not statistically significant, joint stiffness measurements were different (p < 0.15) among groups (3.0 N·cm/° ± 1.13 for control and 2.40 N·cm/° ± 0.62 for DKK1 animals), which may be clinically relevant. Altogether, our study demonstrates feasibility of this drug delivery method (OPF + DKK1) and provides preliminary safety data for further assessment of this inhibitor of fibrosis. Further mechanistic characterization of post-traumatic joint contractures (and additional therapeutic reagents that deregulate fibrosis) will permit development of adjuvant therapies that increase joint range of motion and reduce joint stiffness: strategies easily tested using our rabbit model and hydrogel-based delivery system.

Original languageEnglish (US)
Pages (from-to)69-74
Number of pages6
JournalGene Reports
StatePublished - Sep 2017


  • Arthrofibrosis
  • Joint stiffness
  • Knee
  • Range of motion

ASJC Scopus subject areas

  • Genetics


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