Umbilical Cord Blood-Derived Fluid Allograft Product in Foot and Ankle Surgery: Early Results from a Prospective Registry

CATEGORY: Ankle, Ankle Arthritis, Basic Sciences/Biologics, Hindfoot, Surgery INTRODUCTION/PURPOSE: Foot and ankle surgery with bone grafting relieves pain and improves function in patients with hind/midfoot conditions. Umbilical cord blood (UCB) derived allografts have gained recent prominence for their potential in tissue regeneration. UCB is enriched with cytokines which regulate autocrine and paracrine signaling. BioBurst Fluid (BBF) is a UCB derived cellular allograft carefully processed by the patent pending Progenokine™ technique to preserve the unique molecular heterogeneity of UCB. Clinical study is being conducted to determine the safety and efficacy of BBF administered in patients undergoing foot and ankle surgery (NCT03077256). Here we report our initial data from this ongoing study. In vitro biochemical characterization of BBF further established the osteogenic potential of this allograft and provided mechanistic link to its clinical efficiency. METHODS: 57 patients undergoing surgery with concomitant BBF administration were enrolled in an IRB-approved study, the selection criteria being not to exclude anyone. Data obtained from 21 of the 57 enrolled patients completing their 6-month post- op is reported. The prospective registry recorded patient demographics, comorbidities, symptoms, fusion status, pain, pain medication use, and neurological status up to 6 months post-op. Surgical, immediate post-op, and follow-up complications were also recorded. Fusion was assessed at 3 and 6 months via anteroposterior and lateral x-rays. Pain and function were assessed with Visual Analogue Scale/VAS and modified Odom’s criteria. Neurological status was recorded as improved, maintained, or worse. Narcotic and NSAID use were rated as increased/same or decreased/discontinued. For in vitro characterization of BBF, standard cell-biology methods were employed using MSC as model system. Cytokine concentration in 30 random BBF lots was determined by Luminex multiplex assay. All data are analyzed using appropriate statistical tools. RESULTS: No complications from administration of BBF were seen intra-operatively and during follow-up. Successful fusion (>50% incorporation) was achieved in 20/21 patients (95%) with 8 patients having fusion by 3 months. One non-union occurred in an HIV positive patient. VAS pain score improved clinically from pre-op at 3 months (-3.3, p<0.0001) and 6 months (-4.4, p<0.0001). Odom’s criteria success were 84% and 96% patients at 3 and 6 months respectively. All narcotics were discontinued by 3 months, NSAID use decreased or discontinued in 75% and 82% of patients at 3 and 6 months respectively. Neurological status improved in 20/21 (95%) patients with 1 patient maintained. Our mechanistic study quantified 44 cytokines in BBF which positively impacted proliferation, migration, and osteogenic differentiation of MSCs. CONCLUSION: No adverse-event reports established the clinical safety of BBF. Extrapolation of this initial data suggests early and high rates of successful fusion and better than expected clinical outcomes in patients using BBF in foot and ankle procedures. These positive outcomes may be attributed to BBF’s molecular profile of anti-inflammatory cytokines which help in pain mitigation. Growth factors and chemokines present in BBF induce host MSC to participate in proliferation, recruitment, and osteogenic differentiation which contribute to bone regeneration and fusion.