Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study.

BACKGROUND: Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA. METHODS AND ANALYSIS: This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration. DISCUSSION: This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA. TRIAL REGISTRATION: Registered on July 21, 2021. ClinicalTrials.gov NCT04971798.

Radiofrequency ablation near the bone-muscle interface alters soft tissue lesion dimensions.

BACKGROUND AND OBJECTIVES: Radiofrequency (RF) lesions are safe and effective in the treatment of spine pain; however, models developed to study factors affecting lesion dimensions have been performed in homogeneous media that may not accurately simulate human anatomy and electrophysiology. We present a novel ex vivo porcine model for performing RF lesion studies and report the influence of bone on projection of RF ablation lesions into soft tissue. METHODS: Radiofrequency lesions were performed in porcine rib specimens using monopolar 18-gauge, 10-mm straight active tip cannula, with a lesion temperature of 80°C for 150 seconds. Ten lesions were performed in pure porcine muscle tissue and abutting porcine rib bone with surrounding muscle. Lesions were exposed with dissection and measured with digital calipers. RESULTS: Maximal effective lesion radius approximately doubled against the bone compared with the pure muscle group (mean, 5.65 mm [95% CI, 5.43-5.87 mm] vs 2.68 mm [95% CI, 2.55-2.81 mm], P < .0001), although this was seen only in a vertical direction and not horizontally. In addition, the prelesion and postlesion impedance of the bone-muscle interface was consistently higher than the muscle-only interface (mean, 165.6 Ohm [95% CI, 146.6-184.6 Ohm] vs 137.8 Ohm [95% CI, 135.5-140.1 Ohm], P = 0.004; 144.3 Ohm [95% CI, 134.3-154.3 Ohm] vs 124.3 Ohm [95% CI, 119.3-129.3 Ohm], P = 0.001). Other dimensions and estimated volume were not significantly different. CONCLUSIONS: Bone adjacent to RF lesions alters the surrounding electrophysiological environment causing RF lesions to project further perpendicularly from the needle axis, vertically to bone, than previously expected. This phenomenon should be considered in the future modeling and clinical practice of RF.