Calcium phosphates enhanced with liposomes - the future of bone regeneration and drug delivery.

Effective healing and regeneration of various bone defects is still a major challenge and concern in modern medicine. Calcium phosphates have emerged as extensively studied bone substitute materials due to their structural and chemical resemblance to the mineral phase of bone, along with their versatile properties. Calcium phosphates present promising biological characteristics that make them suitable for bone substitution, but a critical limitation lies in their low osteoinductivity. To supplement these materials with properties that promote bone regeneration, prevent infections, and cure bone diseases locally, calcium phosphates can be biologically and therapeutically modified. A promising approach involves combining calcium phosphates with drug-containing liposomes, renowned for their high biocompatibility and ability to provide controlled and sustained drug delivery. Surprisingly, there is a lack of research focused on liposome-calcium phosphate composites, where liposomes are dispersed within a calcium phosphate matrix. This raises the question of why such studies are limited. In order to provide a comprehensive overview of existing liposome and calcium phosphate composites as bioactive substance delivery systems, the authors review the literature exploring the interactions between calcium phosphates and liposomes. Additionally, it seeks to identify potential interactions between calcium ions and liposomes, which may impact the feasibility of developing liposome-containing calcium phosphate composite materials. Liposome capacity to protect bioactive compounds and facilitate localized treatment can be particularly valuable in scenarios involving bone regeneration, infection prevention, and the management of bone diseases. This review explores the implications of liposomes and calcium phosphate material containing liposomes on drug delivery, bioavailability, and stability, offering insights into their advantages.

Antimicrobial and Antibiofilm Properties of Latvian Honey against Causative Agents of Wound Infections.

Honey is widely used in traditional medicine and modern wound healing biomaterial research as a broad-spectrum antimicrobial, anti-inflammatory and antioxidant agent. The study's objectives were to evaluate the antibacterial activity and polyphenolic profiles of 40 monofloral honey samples collected from beekeepers in the territory of Latvia. The antimicrobial and antifungal activity of Latvian honey samples were compared with commercial Manuka honey and the honey analogue sugar solutions-carbohydrate mixture and tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, clinical isolates Extended-Spectrum Beta-Lactamases produced Escherichia coli, Methicillin-resistant Staphylococcus aureus and Candida albicans. Antimicrobial activity was evaluated with the well-diffusion method (80% honey solution w/v) and microdilution method. The honey samples with the highest antimicrobial potential were tested to prevent biofilm development and activity against a preformed biofilm. The principal component analysis of the antimicrobial properties of honey samples vs. polyphenolic profile was performed. Eleven honey samples exhibited antibacterial activity to all investigated bacteria. The antibacterial effect of the samples was most significant on the Gram-positive bacteria compared to the studied Gram-negative bacteria. Latvian honey presents promising potential for use in wound healing biomaterials, opening the possibility of achieving long-term antibacterial effects.

Injectable Platelet-Rich Fibrin as a Drug Carrier Increases the Antibacterial Susceptibility of Antibiotic-Clindamycin Phosphate.

The aim of this study was to investigate the change in clindamycin phosphate antibacterial properties against Gram-positive bacteria using the platelet-rich fibrin as a carrier matrix, and evaluate the changes in the antibiotic within the matrix. The antibacterial properties of CLP and its combination with PRF were tested in a microdilution test against reference cultures and clinical isolates of Staphylococcus aureus (S. aureus) or Staphylococcus epidermidis (S. epidermidis). Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) analysis was done to evaluate the changes in the PRF_CLP matrix. Release kinetics of CLP was defined with ultra-performance liquid chromatography (UPLC). According to FTIR data, the use of PRF as a carrier for CLP ensured the structural changes in the CLP toward a more active form of clindamycin. A significant decrease in minimal bactericidal concentration values (from 1000 µg/mL to 62 µg/mL) against reference cultures and clinical isolates of S. aureus and S. epidermidis was observed for the CLP and PRF samples if compared to pure CLP solution. In vitro cell viability tests showed that PRF and PRF with CLP have higher cell viability than 70% after 24 h and 48 h time points. This article indicates that CLP in combination with PRF showed higher antibacterial activity against S. aureus and S. epidermidis compared to pure CLP solution. This modified PRF could be used as a novel method to increase drug delivery and efficacy, and to reduce the risk of postoperative infection.

Calcium Phosphate/Hyaluronic Acid Composite Hydrogels for Local Antiosteoporotic Drug Delivery.

Despite the bone ability of self-regeneration, large bone defects require surgical intervention. Likewise, when it comes to osteoporotic bone fractures, new approaches should be considered a supportive mechanism for the surgery. In recent years, more and more attention has been attracted to advanced drug delivery systems for local osteoporosis treatment, combining appropriate biomaterials with antiosteoporotic drugs, allowing simultaneously to regenerate the bone and locally treat the osteoporosis. Within the current research, hyaluronic acid/strontium ranelate (HA/SrRan), HA/calcium phosphate nanoparticles (HA/CaP NPs), and HA/CaP NPs/SrRan hydrogels were prepared. The effect of CaP and SrRan presence in the composites on the swelling behavior, gel fraction, molecular structure, microstructure, and SrRan and Sr2+ release, as well as in vitro cell viability was evaluated. Obtained results revealed that the route of CaP nanoparticle incorporation into the HA matrix had a significant effect on the hydrogel gel fraction, rheological properties, swelling behavior, and microstructure. Nevertheless, it had a negligible effect on the release kinetics of SrRan and Sr2+. The highest cell (3T3) viability (>80%) was observed for HA hydrogels, with and without SrRan. Moreover, the positive effect of SrRan on 3T3 cells was also demonstrated, showing a significant increase (up to 50%) in cell viability if the used concentrations of SrRan were in the range of 0.05-0.2 µg/ml.

Enzymatically Crosslinked In Situ Synthesized Silk/Gelatin/Calcium Phosphate Hydrogels for Drug Delivery.

Our research focuses on combining the valuable properties of silk fibroin (SF) and calcium phosphate (CaP). SF is a natural protein with an easily modifiable structure; CaP is a mineral found in the human body. Most of the new age biocomposites lack interaction between organic/inorganic phase, thus SF/CaP composite could not only mimic the natural bone, but could also be used to make drug delivery systems as well, which can ensure both healing and regeneration. CaP was synthesized in situ in SF at different pH values, and then crosslinked with gelatin (G), horseradish peroxide (HRP), and hydrogen peroxide (H2O2). In addition, dexamethasone phosphate (DEX) was incorporated in the hydrogel and drug delivery kinetics was studied. Hydrogel made at pH 10.0 was found to have the highest gel fraction 110.24%, swelling degree 956.32%, and sustained drug delivery for 72 h. The highest cell viability was observed for the hydrogel, which contained brushite (pH 6)-512.43%.