Development of Vancomycin Delivery Systems Based on Autologous 3D Platelet-Rich Fibrin Matrices for Bone Tissue Engineering

Abstract

Autologous platelet-rich fibrin (PRF) is derived from the blood and its use in the bone tissue engineering has emerged as an effective strategy for novel drug and growth factor delivery systems. Studies have approved that combined therapy with PRF ensures higher biological outcomes, but patients still undergo additional treatment with antibiotic drugs before, during, and even after the implantation of biomaterials with PRF. These systematically used drugs spread throughout the blood and lead not only to positive effects but may also induce adverse side effects on healthy tissues. Vancomycin hydrochloride (VANKA) is used to treat severe Staphylococcal infections but its absorption in the target tissue after oral administration is low; therefore, in this study, we have developed and analyzed two kinds of VANKA carriers—liposomes and microparticles in 3D PRF matrices. The adjustment, characterization, and analysis of VANKA carriers in 3D PRF scaffolds is carried out in terms of encapsulation efficiency, drug release kinetics and antibacterial activity; furthermore, we have studied the micro- and macrostructure of the scaffolds with microtomography.

Evaluation of advanced platelet-rich fibrin (PRF) as a bio-carrier for ampicillin/sulbactam

“…I-PRF without the addition of antibiotics served as a control group. A sustainable antibiotic release was only shown in group I when antibiotics were added to the fabricated i-PRF before clot was formed [32,36]. Another study by Polak et al depicted antibacterial properties of PRF, when patients´ blood is incorporated with antibiotic drugs before the centrifugation process.…”

“…The situation is different when a specific antibiotic is desired, but systemically application is not possible, for example, when the side effects exceed the positive benefit or when it is a reserve antibiotic, as with vancomycin or gentamicin. In those cases, the incorporation of patient's blood after blood sampling could be beneficial 1 3 [20,21,32,33,36,37]. Different approaches for antibiotic instillation are described in the literature.…”

Fibrin-Rhamnogalacturonan I Composite Gel for Therapeutic Enzyme Delivery to Intestinal Tumors

“…The resulting fibrin–polysaccharide composite gel is convenient to use, as it allows implantation in a liquid form, followed by in situ hardening, but can also be used orally in the form of preformatted capsules, since it showed high resistance to the acidic pH of the stomach. The absence of a toxic effect on normal cells of its ingredients, these being fibrin and rhamnogalacturonan I (potato galactan), as well as DPPC liposomes, was previously established [ 11 , 31 , 32 ].…”

“…The possibility of using fibrin clots as a drug carrier has been studied in a number of works [ 31 , 32 , 33 ]. It was shown that the drug retention time depends on the pore size, the resistance of the fibrin matrix to the external environment, and the interaction of the drug with fibrin.…”

Platelet-rich fibrin as an autologous biomaterial for bone regeneration: mechanisms, applications, optimization

“…The concentration of VANKA release in the PRF/PLGA_µC_VANKA scaffold was reduced two-fold relative to the PLGA_µC_VANKA scaffold, indicating that PRF inhibited the rapid release of VANKA. This delivery system ensures controlled VANKA release for 6 ∼ 10 days, with the full antimicrobial effect lasting 48 h ( Dubnika et al, 2021 ). Anton Straub et al collected blood from subjects 10 min after intravenous injection of ampicillin/sulbactam and prepared PRF by centrifugation; the antibiotic concentration in PRF was comparable to the blood concentration, and PRF scaffolds loaded with ampicillin/sulbactam showed significant antibacterial effects against Haemophilus influenza , Staphylococcus aureus , and Streptococcus pneumoniae ( Straub et al, 2022 ).…”