Bone grafting and reconstruction are still challenging in clinical practice because of the limitations of bone autografts and the drawbacks of currently approved bone substitutes. We thus developed a gene-activated bone substitute based on octacalcium phosphate and naked plasmid DNA carrying the vascular endothelial growth factor gene. This advanced combined therapy medicinal product had no cytotoxic effects in vitro, slightly decreased bone marrow mesenchymal stromal cell (MSC) doubling time, and was characterized by a prolonged level of gene construct delivery in vivo in a luciferase bioimaging assay. In the model of critically sized cranial bone defects in rabbits, the gene-activated matrix increased bone tissue formation through angiogenesis induction. After preclinical studies, we conducted an open-label non-randomized clinical trial (NCT03076138). The primary study outcome was the proportion of patients with newly formed bone tissue within the surgical area as measured by computed tomography within 6 months after surgery. The main secondary outcomes included frequencies of adverse events (AEs) and serious adverse events (SAEs) as well as the surgical failure rate. After completing the clinical trial, the patients had dental implants placed in the bone grafting area, and trephine biopsy samples were collected. In total, 20 patients with alveolar ridge atrophy (n = 16) and jaw bone defects (n = 4) were enrolled in the study. There were no AEs or SAEs during the clinical trial or the follow-up period (30 months). In all patients, newly formed tissues with a bone density of 908.13 ± 114.40 HU were detected within the zone of bone grafting. There were no significant differences between the subgroups of patients with atrophy and bone defects: 915.28 ± 125.85 and 879.56 ± 48.36 HU, respectively (p = 0.60). Histological analysis showed that the bone grafting area comprised newly formed bone tissue with some fragments of the gene-activated bone substitute partially resorbed and integrated with bone, without fibrous tissue in between. The preclinical data and clinical trial results proved the feasibility, safety, and efficacy of the investigated material for jaw bone grafting, allowing us to bring the world's first gene-activated bone substitute from bench to bedside.
The development direction of bioresorbable fixing structures is currently very relevant because it corresponds to the priority areas in worldwide biotechnology development. Magnesium (Mg)-based alloys are gaining high levels of attention due to their promising potential use as the basis for fixating structures. These alloys can be an alternative to non-degradable metal implants in orthopedics, maxillofacial surgery, neurosurgery, and veterinary medicine. In our study, we formulated a Mg-2Zn-2Ga alloy, prepared pins, and analyzed their biodegradation level based on SEM (scanning electron microscopy) and EDX (energy-dispersive X-ray analysis) after carrying out an experimental study on rats. We assessed the resorption parameters 1, 3, and 6 months after surgery. In general, the biodegradation process was characterized by the systematic development of newly formed bone tissue. Our results showed that Mg-2Zn-2Ga magnesium alloys are suitable for clinical applications.
Aim. To analyse the effi ciency of osteoplastic material application in order to reduce the resorption level after tooth extraction in the preimplantation period according to the data of cone beam computed tomography.Materials and methods. The study involved 80 patients who were divided into 4 equal groups depending on the preservation material used. The fi rst group was treated with Cerabone (Botiss, Germany) xenomaterial based on natural bovine bone. Plasma enriched with PRGF growth factors obtained by the BTI Endoret (Spain) technology was used for the patients of the second group. The third group consisted of patients who underwent a socket preservation of the extracted tooth with a powdered autologous dentin matrix (ADM) obtained from their own tooth. In the fourth group, bone-plastic material based on hydroxyapatite with Collapan-L lincomycin hydrochloride (Intermedapatit, Russia) was used to prevent socket resorption. All patients had a cone beam computed tomography of the maxillofacial region before the extraction and 3 months after the preservation in order to evaluate the level of bone resorption. After the installation of dental implants, a comparative assessment of the bone resorption level in the vertical and horizontal directions before tooth extraction and in the preimplantation period was carried out.Results. The smallest level of vertical bone resorption after socket preservation was observed in group 1 (Cerabone) and group 3 (ADM). The median value of the socket resorption level in group 1 was 0.7 mm (8.54 %) in the vertical direction and 0.5 mm (9.45 %) in horizontal measurement as compared to the level of bone tissue before tooth extraction. Similar indicators were observed in the group using an autologous dentin matrix. The vertical decrease in the socket bone tissue was 0.61 mm (7.75 %), horizontal — 0.51 mm (6.2 %). The level of bone resorption was signifi cantly higher using two other materials.Conclusions. The use of three-dimensional radiation research methods allows a comprehensive assessment of the bone tissue volume to be carried out, which in turn determines the choice of the dental implant size, the need for further bone-plastic surgery to increase the width/height of the alveolar ridge. The use of cone beam computed tomography showed that the most optimal results can be obtained by introducing Cerabone material into the socket of the extracted tooth, as well as using the innovative method of preservation with the patient’s own powdered tooth (ADM).
Fixation screws and other temporary magnesium alloy fixation devices are used in orthopedic practice because of their biodegradability, biocompatibility and acceptable biodegradation rates. The substitution of dissolving implant by tissues during the healing process is one of the main requirements for biodegradable implants. Previously, clinical tests showed the effectiveness of Ga ions on bone tissue regeneration. This work is the first systematic study on the corrosion rate and biocompatibility of Mg–Zn–Ga–(Y) alloys prepared by hot extrusion, where Ga is an additional major alloying element, efficient as a bone-resorption inhibitor. Most investigated alloys have a low corrosion rate in Hanks’ solution close to ~0.2 mm/year. No cytotoxic effects of Mg–2Zn–2Ga (wt.%) alloy on MG63 cells were observed. Thus, considering the high corrosion resistance and good biocompatibility, the Mg–2Zn–2Ga alloy is possible for applications in osteosynthesis implants with improved bone tissue regeneration ability.
In the present study, pins made from the novel Mg-2Zn-2Ga alloy were installed within the femoral bones of six Wistar rats. The level of bioresorption was assessed after 1, 3, and 6 months by radiography, histology, SEM, and EDX. Significant bioresorption was evident after 3 months, and complete dissolution of the pins occurred at 6 months after the installation. No pronounced gas cavities could be found at the pin installation sites throughout the postoperative period. The animals’ blood parameters showed no signs of inflammation or toxication. These findings are sufficiently encouraging to motivate further research to broaden the experimental coverage to increase the number of observed animals and to conduct tests involving other, larger animals.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.