Antimicrobial Synthetic Bone Grafts

The Use of Antimicrobial Synthetic Bone Grafts in the Treatment of Bone Infection

This project aims to produce synthetic bone tissue graft that supports bone regeneration and combats infection simultaneously, according to industry standards and regulations. This original and high value added biomaterial "silver doped calcium phosphate based synthetic bone tissue " will be used in clinical trials in patients with osteomyelitis and implant-related infections for the treatment.

Chronic bone infections are one of the most important problems in orthopedic surgery and are not just a problem of developed societies. When open fracture cases, which may get infected in 1-50%, implant-related infections and diabetic foot ulcer cases are taken into consideration, osteomyelitis will be seen as a very common problem all over the world. Multiple surgeries, long-term use of antibiotics and the high costs affects all societies. The use of synthetic bone grafts is growing faster than the natural bone grafts in the world. USA has spent 246 million US dollars for the use of synthetic bone graft in 2010. For the treatment of bone infections antibiotic impregnated synthetic bone grafts with different characteristics are used. Although these antibiotic impregnated synthetic bone grafts are superior compared to antibiotic bone cement with the implementation of different antibiotics and to be absorbable but they cannot show optimum benefit because the release of antibiotics is not due to host matrix degradation but diffusion control. The other issue to be considered as this regard that the development of microbial resistance to these antibiotics which is also a serious problem. Innovative synthetic bone graft with better contribution of the needs of mechanical properties, depending on the applied bone region, optimized antimicrobial activity and bone tissue regeneration are needed.

In this study, it will be determined whether this silver ion -doped antimicrobial synthetic bone graft that has the capacity to fill the bone voids that may occur in chronic bone infection during disease process or after surgical debridement, also has the capacity to treat the infection in the bone will be used in 12 patients who had been diagnosed as chronic osteomyelitis to see if it cause any unwanted side effect in normal usage conditions and generates unacceptable risks. Clinical, laboratory and radiological investigations will be used to demonstrate the healing of the infections and the cavities in the bone. Blood and urine levels of silver will be detected from patients.

Antimicrobial activity of silver is well-known. The effectiveness of the silver and potential toxicity is related to the dose of silver and application form. In orthopedics, the use of silver is mostly limited to elemental silver coating of metal implants. There is no biotechnologic approach manufactured silver ion -doped calcium phosphate -based synthetic bone graft in the health sector yet. Ionic silver has advantages such as low toxicity, no tolerance of silver against bacteria, and strong antibacterial activity. The trapping of silver ions in the calcium phosphate based ceramic structure overcomes the other systems with its controlled release and its ability to be effective at minimum doses. The project is an original work since it will contribute to bone regeneration while at the same time removing the infection.

Study Overview

• Status: Completed
• Conditions: Bone Infection; Bone Graft Infection
• Intervention / Treatment: Device: antimicrobial synthetic bone graft; Device: parentaral antimicrobials and pure bone grafts

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Turkey
  • Eskişehir, Turkey, 26480
    • Eskişehir Osmangazi University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with chronic osteomyelitis, infected non-union or implant-associated infection with an indication for artificial bone grafting who read and accept the Informed consent.
• Male and female patients older than 18 years
• Patients without heart, lung, renal or hepatic failure, epilepsy, cerebrovascular attack or ischemia
• Patients who are not allergic to antibiotics
• Patients with additional immunosuppression such as malignancy, diabetes mellitus, poly travma and open fractures
• Patients using oral or parenteral corticosteroids, methotrexate, cyclosporine or other immunosuppressive drugs

Exclusion Criteria:

• Patients who have not accepted the method.
• Patients outside the working age range
• Pregnant women
• Patients with heart, lung, renal, hepatic failure, epilepsy, cerebrovascular attack or ischemia
• Patients with allergy to antibiotics
• Patients with another silvery implant in the body like a silver-coated implant
• Patients with a history of known allergies or hypersensitivity to silver

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: antimicrobial synthetic bone graft; This group will have parenteral antibiotics and antimicrobial (silver ions) synthetic bone graft	Device: antimicrobial synthetic bone graft; It will be determined whether the silver ion-doped antimicrobial synthetic bone graft that has the capacity to fill the bone voids also has the capacity to treat the infection in the bone in 12 patients with chronic osteomyelitis
Active Comparator: parenteral antibiotics with pure synthetic bone graft; This group will have parenteral antibiotics and pure synthetic bone graft	Device: parentaral antimicrobials and pure bone grafts; Historical data of the department will be used for comparison of the results

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bony healing of the cavities in the bone	Number of Participants with bony healing of the cavities in the bone by x-ray	12 months

Collaborators and Investigators

• Sponsor: Eskisehir Osmangazi University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): August 15, 2021

Study Registration Dates

• First Submitted: March 31, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Bacterial Agents; Anti-Infective Agents
• Other Study ID Numbers: 2019-2491

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: After the publication of the study nidividual participant data (IPD) will be available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No