Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2

Abstract

Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydrideester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 mg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation.

Biodegradable Polymer Membranes Applied in Guided Bone/Tissue Regeneration: A Review

“…SAPAE have been synthesized by chemically incorporating salicylic acid, a nonsteroidal anti-inflammatory drug, that reduces the production of pro-inflammatory cytokines within a polyanhydride [ 145 ]. Subramanian et al [ 146 ] tested SAPAE membrane as a physical barrier and localized salicylic acid delivery system to restrict BMP-2 activity to a specified region. The data indicated that SAPAE polymer membranes have potential application in GBR and GTR procedures and as a barrier to excessive bone formation for diabetes.…”

Vascular tissue engineering: Fabrication and characterization of acetylsalicylic acid‐loaded electrospun scaffolds coated with amniotic membrane lysate

“…There are only a few reports on the effects of ASA on stem cell differentiation. With its inhibiting effect on tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production, aspirin has been shown to promote the osteogenesis of bone MSC in vitro, improve calvarial bone repair in vivo (Cao et al, 2015), and limit ectopic bone formation caused by BMP-2 treatment (Subramanian et al, 2015). (Alcaraz et al, 2015).…”

Physicochemical and Biological Characterisation of Diclofenac Oligomeric Poly(3-hydroxyoctanoate) Hybrids as β-TCP Ceramics Modifiers for Bone Tissue Regeneration

“…Subramanian et al produced thin flexible electrically driven membranes consisting of a copolymer of salicylic acid/succinic anhydride (SAPAE) and polycaprolactone (PCL) for use in bone tissue regeneration. These membranes were able to release salicylic acid during hydrolysis of one of the polymeric components [ 14 ]. Some studies described the effects of DIC release on reducing host response to the implanted foreign body.…”