Release Kinetics in PRF Versus GEM21S With and Without Bone Substitutes: An In Vitro Analysis

NCT ID: NCT04964466

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 5 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-08-31
• Study Completion Date: 2026-12-31

Brief Summary

This study is seeking to evaluate that platelet-derived growth factor-BB (PDGF-BB) is a proven wound healing and osteogenic protein that plays a critical role in wound healing and previous research has demonstrated a non-linear response where higher dosages produced less effect. As Platelet Rich Fibrin (PRF) contains numerous platelets, it contains PDGF-BB, but at levels lower than in the commercially available product and with inter-individual variation, GEM21S. To achieve both ideal handling and achieve ideal levels of PDGF-BB, there is a rationale to add GEM 21S recombinant human platelet-derived growth factor-BB (rhPDGF) to a bone graft prior to making "sticky bone".

Detailed Description

Innovations in biomedicine and recombinant protein technology show promising advances for the regeneration of advanced alveolar defects. Recombinant growth factors and biologics encourage minimally invasive procedures with improved clinical outcomes/healing times in complex oral surgery procedures. PDGF-BB is a growth factor that is known to be a potent mitogen and chemotactic agent for cells important in wound healing and bone regeneration. PDGF-BB is also a strong angiogenic agent. These properties provide a solid biological mechanism of action and rationale for the widespread use of rhPDGF-BB in dental and orthopedic surgery, as well as in the treatment of difficult soft tissue wounds. Practically, two sources of supra-physiologic levels PDGF-BB are currently available for use in dental hard and soft tissue defects: 1) Platelet concentrates (PRF/PRF); and 2) GEM 21S, which contains recombinant human PDGF-BB (rhPDGF-BB). Platelet rich plasma was first introduced to dentistry in 1998 by Robert Marx. Since then, other autologous products have evolved. Platelet rich fibrin (PRF) is one that is used daily in various clinical scenarios, including guided bone regeneration. The rationale for its use is due to the supraphysiologic concentration of growth factors (ie PDGF-BB) and cells to enhance would healing. Clinicians also frequently incorporate PRF to bone grating materials to improve handling properties of the graft material, also referred to as "sticky bone". However, the literature varies greatly on the believed mechanism of action and the therapeutic benefits claimed by their supporters. The rationale for this proposed study that PDGF-BB is a proven wound healing and osteogenic protein, but there are clinically insignificant amounts of PDGF-BB in PRF. Therefore, there is a rationale to add GEM 21S (rhPDGF) to a bone graft prior to making "sticky bone" with PRF. This would provide clinicians the benefits of a clinically proven and consistent dose of rhPDGF to improve wound healing and bone formation in conjunction with the benefits of the improved handling (i.e. sticky bone) from the addition of the PRF.

Conditions

Bone Loss

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Release kinetics of PDGF-BB in rhPDGF-BB + PRF + bone substitutes

The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Release kinetics of PDGF-BB in rhPDGF-BB + PRF + bone substitutes

Intervention Type: BIOLOGICAL

The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Amount of PDGF-BB in PRF preparation vs. GEM21

The release kinetics of PDGF-BB will be assessed for one PRF preparation from each of the six individual participants and one GEM 21S sample. The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Amount of PDGF-BB in PRF preparation vs. GEM21

Intervention Type: BIOLOGICAL

The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

PDGF-BB available in PRF + bone substitutes vs. rhPDGF-BB+ bone substitutes

Growth factor release assessments will be made to determine the PDGF-BB present in the six prepared samples of the following: 1) PRF + mineralized freeze-dried corticocancellous allograft, 2) PRF + xenograft, and 3) PRF + B-TCP. Assessments will also be made for one sample of each of the following: 1) rhPDGF-BB + freeze-dried bone allograft, 2) rhPDGF-BB + xenograft, and 3) rhPDGF-BB+ B-TCP preparation. This assessment will be made at 60 minutes following the incorporation of the bone graft materials. During this time period, the samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At 60 minutes after preparation, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Amount of PDGF-BB available in PRF + bone substitutes vs. rhPDGF-BB+ bone substitutes following preparation

Intervention Type: BIOLOGICAL

Growth factor release assessments will be made to determine the PDGF-BB present in the six prepared samples of the following: 1) PRF + mineralized freeze-dried corticocancellous allograft, 2) PRF + xenograft, and 3) PRF + B-TCP. Assessments will also be made for one sample of each of the following: 1) rhPDGF-BB + freeze-dried bone allograft, 2) rhPDGF-BB + xenograft, and 3) rhPDGF-BB+ B-TCP preparation. This assessment will be made at 60 minutes following the incorporation of the bone graft materials. During this time period, the samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At 60 minutes after preparation, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

: Release kinetics of PDGF-BB in PRF + bone substitutes vs. rhPDGF-BB + bone substitutes

The release kinetics of PDGF-BB will be assessed for six preparations of each of following: 1) PRF+ mineralized freeze-dried corticocancellous allograft, 2) PRF + bone xenograft, and 3) PRF + B-TCP. The release kinetics of PDGF-BB will also be assessed for one preparations of each of following: 1) rhPDGF-BB + mineralized freeze-dried corticocancellous allograft, 2) rhPDGF-BB + bone xenograft, 3) rhPDGF-BB + TCP. The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Release kinetics of PDGF-BB in PRF + bone substitutes vs. rhPDGF-BB + bone substitutes

Intervention Type: BIOLOGICAL

The release kinetics of PDGF-BB will be assessed for six preparations of each of following: 1) PRF+ mineralized freeze-dried corticocancellous allograft, 2) PRF + bone xenograft, and 3) PRF + B-TCP. The release kinetics of PDGF-BB will also be assessed for one preparations of each of following: 1) rhPDGF-BB + mineralized freeze-dried corticocancellous allograft, 2) rhPDGF-BB + bone xenograft, 3) rhPDGF-BB + TCP. The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Interventions

Amount of PDGF-BB in PRF preparation vs. GEM21

The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Intervention Type: BIOLOGICAL

Amount of PDGF-BB available in PRF + bone substitutes vs. rhPDGF-BB+ bone substitutes following preparation

Growth factor release assessments will be made to determine the PDGF-BB present in the six prepared samples of the following: 1) PRF + mineralized freeze-dried corticocancellous allograft, 2) PRF + xenograft, and 3) PRF + B-TCP. Assessments will also be made for one sample of each of the following: 1) rhPDGF-BB + freeze-dried bone allograft, 2) rhPDGF-BB + xenograft, and 3) rhPDGF-BB+ B-TCP preparation. This assessment will be made at 60 minutes following the incorporation of the bone graft materials. During this time period, the samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At 60 minutes after preparation, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Intervention Type: BIOLOGICAL

Release kinetics of PDGF-BB in PRF + bone substitutes vs. rhPDGF-BB + bone substitutes

The release kinetics of PDGF-BB will be assessed for six preparations of each of following: 1) PRF+ mineralized freeze-dried corticocancellous allograft, 2) PRF + bone xenograft, and 3) PRF + B-TCP. The release kinetics of PDGF-BB will also be assessed for one preparations of each of following: 1) rhPDGF-BB + mineralized freeze-dried corticocancellous allograft, 2) rhPDGF-BB + bone xenograft, 3) rhPDGF-BB + TCP. The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Intervention Type: BIOLOGICAL

Release kinetics of PDGF-BB in rhPDGF-BB + PRF + bone substitutes

The quantification will be performed at 60 minutes, 8 hours, 1 day, 3 days, and 10 days. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol. The samples will each be placed in a cell incubator at 37°C to allow for growth factor release into a phosphate-buffered saline. At each desired time point assessment, 2 ml of the sample will be collected, frozen, and replaced with 2 ml of additional phosphate-buffered saline. The protein quantification will be carried out using ELISA assay according to manufacturer's protocol.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• English speaking
• At least 18 years old
• Able to read and understand informed consent document
• Systemically healthy, non-smoker, no medications

Exclusion Criteria

• Non-English speaking
• Less than 18 years old
• Smokers/tobacco users (>10 cigarettes/day)
• Patients with systemic pathologies or conditions contraindicating oral surgical procedures or adversely affecting healing

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Maria L. Geisinger, DDS, MS

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

UAB-Perio

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-300005971

Identifier Type: -

Identifier Source: org_study_id