World's First Clinical Case of Gene-Activated Bone Substitute Application

I Y Bozo, R V Deev, A Y Drobyshev, A A Isaev, I I Eremin, I Y Bozo, R V Deev, A Y Drobyshev, A A Isaev, I I Eremin

Abstract

Treatment of patients with large bone defects is a complex clinical problem. We have initiated the first clinical study of a gene-activated bone substitute composed of the collagen-hydroxyapatite scaffold and plasmid DNA encoding vascular endothelial growth factor. The first patient with two nonunions of previously reconstructed mandible was enrolled into the study. Scar tissues were excised; bone defects (5-14 mm) between the mandibular fragments and nonvascularized rib-bone autograft were filled in with the gene-activated bone substitute. No adverse events were observed during 12 months of follow-up. In 3 months, the average density of newly formed tissues within the implantation zone was 402.21 ± 84.40 and 447.68 ± 106.75 HU in the frontal and distal regions, respectively, which correlated with the density of spongy bone. Complete distal bone defect repair with vestibular and lingual cortical plates formation was observed in 6 and 12 months after surgery; thereby the posterior nonunion was successfully eliminated. However, there was partial resorption of the proximal edge of the autograft entailed to relapse of the anterior nonunion. Thus, the first clinical data on the safety and efficacy of the gene-activated bone substitute were obtained. Given a high complexity of the clinical situation the treatment, results might be considered as promising. NCT02293031.

Conflict of interest statement

The authors declare that there are no competing interests regarding the publication of this paper. I. Y. Bozo, A. A. Isaev, and R. V. Deev are employees of the PJSC “Human Stem Cells Institute” marketing “Neovasculgen”. A. A. Isaev and R. V. Deev are shareholders of the PJSC “Human Stem Cells Institute.” NextGen Co. Ltd., a sponsor of the clinical trial NCT02293031, is a subsidiary company of PJSC “Human Stem Cells Institute.”

Figures

Figure 1
Figure 1
CT scans of the patient's mandible in the frontal region (a) and within the ramus on the right side (b) prior to the operation and 3, 6, and 12 months after surgery. Arrows indicate nonunions (before operation) and the sites of gene-activated bone substitute implantation.
Figure 2
Figure 2
Intraoperative view: nonunions are removed; mandible fragments and rib autograft are fixed with miniplates; bone defects filled with gene-activated bone substitute.
Figure 3
Figure 3
Panoramic radiography, next day after surgery.
Figure 4
Figure 4
Average density in the regions of nonunions (0) and the sites of gene-activated bone substitute implantation in 3, 6, and 12 months after surgery.
Figure 5
Figure 5
The patient's mandible in different time points after bone grafting with the gene-activated bone substitute: (a) before; (b) 6 months; (c) 12 months. Dental CT; 3D reconstruction with volume rendering 250–2000 HU (titanium constructs are excluded).

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Source: PubMed

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