Release Kinetics of rhBMP-2 Using E-PRF as an Autologous Carrier: An In Vitro Analysis

Bone Loss Clinical Trial

Official title:

Release Kinetics of rhBMP-2 Using E-PRF as an Autologous Carrier: An in Vitro Analysis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04670965
• Other study ID #: IRB-300005939
• Status: Not yet recruiting
• Start date: August 2024
• Est. completion date: December 2026

Study information

• Verified date: December 2023
• Source: University of Alabama at Birmingham
• Contact: Maria Geisinger, DDS,MS
• Phone: 934-4984
• Email: miagdds[@]uab.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is seeking to evaluate the binding of a commercially-available, recombinant human osteoinductive growth factor, rhBMP-2, to a human blood derived product scaffold, enhanced Platelet-rich fibrin (E-PRF), and the release of such a growth factor over time in an in vitro (laboratory) environment. The investigators will compare these release kinetics to those of the FDA approved carrier for rhBMP-2, an absorbable collagen sponge (ACS), a combination of E-PRF and ACS, and E-PRF alone.

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. Recombinant human bone morphogenic protein-2 (rhBMP-2) is a morphogen that is a well-known regulator of bone formation1 and has been widely studied for bone reconstructive treatments.2-6 RhBMP-2 is currently commercially available and loaded on an absorbable collagen sponge (ACS). This recombinant growth factor has been approved by the US Food and Drug Administration as an alternative to autogenous bone grafting in sinus augmentation and localized alveolar ridge augmentation for defects associated with extraction sockets. It is also used off-label for vertical bone augmentation. However, there are limitations of the ACS as a carrier because it is compressible and does not ideally support soft tissues to maintain space for osteogenesis to occur. Furthermore, the release kinetics of rhBMP-2 in a standardized in vitro environment from its ACS carrier are unknown and it is further unknown how such release would compare to the use of other carriers. Subcutaneous implantation in rats and implantation at orthotropic sites in rats and rabbits has also revealed that rhBMP-2-loaded ACS has a release of rhBMP-2 over 21 days with a half-life of 2 days. The use of an alternative delivery system may retain and sequester rhBMPs at the target site and extend its growth factor release over time. This may be clinically relevant as prolonging tissue exposure to an osteoinductive growth factor like rhBMP-2 could extend the period of osteoblastic bone deposition and improve repair at regenerative sites. E-PRF as an autologous carrier for rhBMP-2 may be advantageous based on its resorption properties of up to 4-6 months, as well as its ability to support the healing process due to the slow and gradual release of several growth factors including, PDGF-AA, PDGF-BB, TGF- β1,VEGF, IGF, and EGF. This study aims to quantify the release of rhBMP-2 over a 120 day period with the use of a novel delivery system, E-PRF.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• English speaking
• At least 18 years old
• Must be a patient of the UAB Dental School
• Able to read and understand informed consent document
• Previously treatment planned for a periodontal procedure that will utilize PRF, i.e. requiring venipuncture, as a part of the routine clinical care.

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 wound healing as assessed by Board Certified Periodontal faculty at UAB Department of Periodontology
• Patient-reported serious adverse events reported with venipuncture, blood sample collection, and/or blood donation.

Related Conditions & MeSH terms

• Bone Loss

Intervention

Biological:
• E-PRF/rhBMP-2 (similar ratios)
During its preparation, 1.5 mg/ml rhBMP-2 will be incorporated into standardized samples to assure similar E-PRF to rhBMP-2 ratios. To allow for consistency across all samples, standardized E-PRF volume will be established using formation templates. Following its preparation, the E-PRF/rhBMP2 scaffold will undergo a standard in vitro assay to investigate growth factor release over time (ELISA quantification assay). Briefly, the e-PRF/rhBMP2 scaffold will be placed in a shaking incubator at 37 degree Celsius and assessed for growth factor release of rhBMP-2 over time.
• E-PRF/ACS/rhBMP-2
rhBMP-2 diluted to account for the additional volume from the E-PRF in other samples will be loaded onto lyophilized absorbable collagen sponges as per the package insert. After the addition of the rhBMP-2, the ACS will be cut into 2mm x 2mm pieces and incorporated into the E-PRF membrane. Following its preparation, rhBMP-2 release from the E-PRF/ACS/rhBMP2 scaffold will be quantified using the ELISA quantification assay as described above.
• rhBMP-2/E-PRF
rhBMP-2 diluted to account for the additional volume from the E-PRF in other samples will be loaded onto lyophilized absorbable collagen sponges as per the package insert. Rh-BMP2 release will be quantified using the ELISA quantification assay as described above
• E-PRF only
E-PRF will be prepared and standardized, but no rhBMP-2 will be added to the material. After preparation, the E-PRF scaffold assayed via ELISA quantification assay as described above to determine the release (if any) of intrinsic BMP-2 from the platelet concentrate scaffold.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To quantify any difference between test groups in the release of rhBMP-2 after application to E-PRF and ACS, E-PRF, and ACS.	The quanitites of rhBMP-2 at all time points from all groups will be compared using statistical analysis by two-way ANOVA with Bonferroni test.	From baseline to 6 months
Secondary	To more assess the capability of E-PRF without added rhBMP-2 to release any intrinsic autologous BMP-2 under experimental conditions.	The quanitites of rhBMP-2 at all time points from all groups will be compared using statistical analysis by two-way ANOVA with Bonferroni test.	From baseline to 6 months