Sideritis raeseri-Modified Coatings on Ti-6Al-4V as a Carrier for Controlled Delivery Systems of Active Substances.

The search for the ideal metallic material for an implant is still a difficult challenge for scientists due to the phenomenon of corrosion and the consequent disruption of the implant structure. Prevention is the application of coatings that protect the implant, activate the tissues for faster regeneration, and also prevent inflammation through antibacterial and antiviral effects. The present study focuses on the selection of components for a Ti-6Al-4V alloy coating. These days, researchers are taking an intense interest in extracts of natural origin. It was decided to take a look at Sideritis raeseri, which contains vitamins and valuable elements and is rich in polyphenols, as well as antioxidants. The composition of coatings based on a PEG polymer reinforced with brushite and the S. raeseri extract with the proteins L-carnosine, fibroin, or sericin was developed. The samples were subjected to detailed physiochemical analysis, including potentiometry and electrical conductivity analysis, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and UV-VIS spectroscopy. The study demonstrated that polyphenols were successfully released from the coatings during incubation in vitro. The osteointegration process can be supported by a number of factors, such as the release of polyphenols from implant coatings to prevent bacterial, viral, and fungal infections. Subjecting the samples to 14 days of incubation demonstrated their interactions with the incubation fluids, an ion exchange between the medium and the materials. An analysis of the surface morphology exhibited the presence of brushite crystals and their increased number after incubation, indicating the bioactivity of the formed coatings.

Targeted Clindamycin Delivery Systems: Promising Options for Preventing and Treating Bacterial Infections Using Biomaterials.

Targeted therapy represents a real opportunity to improve the health and lives of patients. Developments in this field are confirmed by the fact that the global market for drug carriers was worth nearly $40 million in 2022. For this reason, materials engineering and the development of new drug carrier compositions for targeted therapy has become a key area of research in pharmaceutical drug delivery in recent years. Ceramics, polymers, and metals, as well as composites, are of great interest, as when they are appropriately processed or combined with each other, it is possible to obtain biomaterials for hard tissues, soft tissues, and skin applications. After appropriate modification, these materials can release the drug directly at the site requiring a therapeutic effect. This brief literature review characterizes routes of drug delivery into the body and discusses biomaterials from different groups, options for their modification with clindamycin, an antibiotic used for infections caused by aerobic and anaerobic Gram-positive bacteria, and different methods for the final processing of carriers. Examples of coating materials for skin wound healing, acne therapy, and bone tissue fillers are given. Furthermore, the reasons why the use of antibiotic therapy is crucial for a smooth and successful recovery and the risks of bacterial infections are explained. It was demonstrated that there is no single proven delivery scheme, and that the drug can be successfully released from different carriers depending on the destination.

Hybrid Coatings Based on Polyvinylpyrrolidone/Polyethylene Glycol Enriched with Collagen and Hydroxyapatite: Incubation Studies and Evaluation of Mechanical and Physiochemical Properties.

Coating materials offers an intriguing solution for imparting inert implants with additional bioactive characteristics without changing underlying parameters such as mechanical strength. Metallic implants like endoprostheses or polymeric implants can be coated with a thin layer of bioactive film capable of stimulating bone-forming cells to proliferate or release a drug. However, irrespective of the final implantation site of such a coating biomaterial, it is necessary to conduct detailed mechanical and physicochemical in vitro analyses to determine its likely behavior under biological conditions. In this study, polymeric and composite coatings with hydroxyapatite obtained under UV light underwent incubation tests in four different artificial biological fluids: simulated body fluid (SBF), artificial saliva, Ringer's fluid, and water (as the reference fluid). The potentiometric and conductometric properties, sorption capacity, and degradation rate of the coatings were examined. Furthermore, their hardness, modulus of elasticity, and deformation were determined. It was demonstrated that the coatings remained stable in SBF liquid at a pH value of around 7.4. In artificial saliva, the greatest degradation of the polymer matrix (ranging between 36.19% and 39.79%) and chipping of hydroxyapatite in the composite coatings were observed. Additionally, the effect of ceramics on sorption capacity was determined, with lower capacity noted with higher HA additions. Moreover, the evaluation of surface morphology supported by elemental microanalysis confirmed the appearance of new apatite layers on the surface as a result of incubation in SBF. Ceramics also influenced mechanical aspects, increasing hardness and modulus of elasticity. For the polymer coatings, the value was 11.48 ± 0.61, while for the composite coating with 15% ceramics, it increased more than eightfold to a value of 93.31 ± 11.18 N/mm2. Based on the conducted studies, the effect of ceramics on the physicochemical as well as mechanical properties of the materials was determined, and their behavior in various biological fluids was evaluated. However, further studies, especially cytotoxicity analyses, are required to determine the potential use of the coatings as biomaterials.

Bioactive Hydrogel Based on Collagen and Hyaluronic Acid Enriched with Freeze-Dried Sheep Placenta for Wound Healing Support.

In an increasingly aging society, there is a growing demand for the development of technology related to tissue regeneration. It involves the development of the appropriate biomaterials whose properties will allow the desired biological response to be obtained. Bioactivity is strongly affected by the proper selection of active ingredients. The aim of this study was to produce bioactive hydrogel materials based on hyaluronic acid and collagen modified by the addition of placenta. These materials were intended for use as dressings, and their physicochemical properties were investigated under simulated biological environmental conditions. The materials were incubated in vitro in different fluids simulating the environment of the human body (e.g., simulated body fluid) and then stored at a temperature close to body temperature. Using an FT-IR spectrophotometer, the functional groups present in the composites were identified. The materials with the added placenta showed an increase in the swelling factor of more than 300%. The results obtained confirmed the potential of using this material as an absorbent dressing. This was indicated by pH and conductometric measurements, sorption, degradation, and surface analysis under an optical microscope. The results of the in vitro biological evaluation confirmed the cytosafety of the tested biomaterials. The tested composites activate monocytes, which may indicate their beneficial properties in the first phases of wound healing. The material proved to be nontoxic and has potential for medical use.

Influence of Drying Technique on Physicochemical Properties of Synthetic Hydroxyapatite and Its Potential Use as a Drug Carrier.

Naturally occurring hydroxyapatite (HA) is the mineral phase of bone tissue. It is characterized by its bioactivity toward stimulating bone cells to proliferate and thus form new apatite layers. For this reason, it is a material commonly used in implantology for filling defects or covering implants (such as endoprostheses). There are several methods to obtain synthetic HA, and by controlling parameters such as temperature, pressure or the drying process, physicochemical parameters of the final powder can be affected. In the present study, HA was obtained by wet precipitation technique and subjected to two different drying methods, determining whether this parameter significantly affects the properties of the final material obtained. Analyzed Fourier-transform infrared spectroscopy (FT-IR) confirmed the presence of functional groups typical for HA. X-ray diffraction analysis (XRD) demonstrated that the materials are partially amorphous; however, the only phase was identified in HA. Scanning electron microscopy (SEM) was used to evaluate the surface morphology and the density, and average grain diameter was measured. Furthermore, HA powders were subjected to modification with the antibiotic clindamycin to determine the potential for use as a carrier for the active substance. The release rate of the drug was determined by high-performance liquid chromatography (HPLC). The differences in the characteristics of the powders were relatively small; however, they affected the rate of drug release from the material as well as the shape of the grains. The method of drying the powders was shown to affect the shape of the grains, as well as the porosity of the sinters prepared from it. A higher amount of clindamycin released into PBS was observed in material with more pores. The materials have demonstrated the potential to be used as a carrier for the active substance; however, further biological, as well as physicochemical, analysis is required.

Clindamycin-Loaded Nanosized Calcium Phosphates Powders as a Carrier of Active Substances.

Bioactive calcium phosphate ceramics (CaPs) are one of the building components of the inorganic part of bones. Synthetic CaPs are frequently used as materials for filling bone defects in the form of pastes or composites; however, their porous structure allows modification with active substances and, thus, subsequent use as a drug carrier for the controlled release of active substances. In this study, four different ceramic powders were compared: commercial hydroxyapatite (HA), TCP, brushite, as well as HA obtained by wet precipitation methods. The ceramic powders were subjected to physicochemical analysis, including FTIR, XRD, and determination of Ca/P molar ratio or porosity. These techniques confirmed that the materials were phase-pure, and the molar ratios of calcium and phosphorus elements were in accordance with the literature. This confirmed the validity of the selected synthesis methods. CaPs were then modified with the antibiotic clindamycin. Drug release was determined on HPLC, and antimicrobial properties were tested against Staphylococcus aureus. The specific surface area of the ceramic has been demonstrated to be a factor in drug release efficiency.

Polymeric and Composite Carriers of Protein and Non-Protein Biomolecules for Application in Bone Tissue Engineering.

Conventional intake of drugs and active substances is most often based on oral intake of an appropriate dose to achieve the desired effect in the affected area or source of pain. In this case, controlling their distribution in the body is difficult, as the substance also reaches other tissues. This phenomenon results in the occurrence of side effects and the need to increase the concentration of the therapeutic substance to ensure it has the desired effect. The scientific field of tissue engineering proposes a solution to this problem, which creates the possibility of designing intelligent systems for delivering active substances precisely to the site of disease conversion. The following review discusses significant current research strategies as well as examples of polymeric and composite carriers for protein and non-protein biomolecules designed for bone tissue regeneration.

Hybrid Polymer-Inorganic Materials with Hyaluronic Acid as Controlled Antibiotic Release Systems.

In recent years, significant developments have taken place in scientific fields such as tissue and materials engineering, which allow for the development of new, intelligent biomaterials. An example of such biomaterials is drug delivery systems that release the active substance directly at the site where the therapeutic effect is required. In this research, polymeric materials and ceramic-polymer composites were developed as carriers for the antibiotic clindamycin. The preparation and characterization of biomaterials based on hyaluronic acid, collagen, and nano brushite obtained using the photocrosslinking technique under UV (ultraviolet) light are described. Physical and chemical analyses of the materials obtained were carried out using Fourier transform infrared spectroscopy (FT-IR) and optical microscopy. The sorption capacities were determined and subjected to in vitro incubation in simulated biological environments such as Ringer's solution, simulated body fluid (SBF), phosphate-buffered saline (PBS), and distilled water. The antibiotic release rate was also measured. The study confirmed higher swelling capacity for materials with no addition of a ceramic phase, thus it can be concluded that brushite inhibits the penetration of the liquid medium into the interior of the samples, leading to faster absorption of the liquid medium. In addition, incubation tests confirmed preliminary biocompatibility. No drastic changes in pH values were observed, which suggests that the materials are stable under these conditions. The release rate of the antibiotic from the biomaterial into the incubation medium was determined using high-pressure liquid chromatography (HPLC). The concentration of the antibiotic in the incubation fluid increased steadily following a 14-day incubation in PBS, indicating continuous antibiotic release. Based on the results, it can be concluded that the developed polymeric material demonstrates potential for use as a carrier for the active substance.

Chemistry towards Biology-Instruct: Snapshot.

The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials.

Preparation, Characterization, and Biocompatibility Assessment of Polymer-Ceramic Composites Loaded with Salvia officinalis Extract.

In the present work, hydroxyapatite-polymer materials were developed. The preparation, as well as characterization of the ceramic-polymer composites based on polyvinylpyrrolidone, sodium alginate, and gelatin were described. The system was enriched with the addition of common sage extract (Salvia officinalis). The antioxidant potential of sage aqueous extract and total polyphenol content was determined. The antioxidant capacity and total phenolic content of extract were equal to 86.06 ± 0.49% and 16.21 ± 0.58 mg gallic acid equivalents per gram of dry weight, respectively. Incubation studies in selected biological liquids were carried out to determine the biomineralization capacity on the surface of the composites and to examine the kinetics of release of the active substances from within the material. As a result of the incubation, a gradual release of the extract over time from the polymer matrix was observed; moreover, the appearance of new apatite layers on the composite surface was recorded as early as after 14 days, which was also confirmed by energy-dispersive X-ray spectroscopy (EDS) microanalysis. The composites were analyzed with Fourier transform infrared spectroscopy (FTIR) spectroscopy, and the morphology was recorded by scanning electron microscope (SEM) imaging. The in vitro biological studies allowed their cytotoxic effect on the reference L929 fibroblasts to be excluded. Further analysis of the biomaterials showed that enrichment with polyphenols does not support the adhesion of L929 cells to the surface of the material. However, the addition of these natural components stimulates human monocytes that constitute the first step of tissue regeneration.

PGS/HAp Microporous Composite Scaffold Obtained in the TIPS-TCL-SL Method: An Innovation for Bone Tissue Engineering.

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (1H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1ß, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.

Composites Based on Hydroxyapatite and Whey Protein Isolate for Applications in Bone Regeneration.

Hydroxyapatite (HAp) is a bioactive ceramic with great potential for the regeneration of the skeletal system. However, its mechanical properties, especially its brittleness, limit its application. Therefore, in order to increase its ability to transmit stresses, it can be combined with a polymer phase, which increases its strength without eliminating the important aspect of bioactivity. The presented work focuses on obtaining organic-inorganic hydrogel materials based on whey protein isolate (WPI) reinforced with nano-HAp powder. The proportion of the ceramic phase was in the range of 0-15%. Firstly, a physicochemical analysis of the materials was performed using XRD, FT-IR and SEM. The hydrogel composites were subjected to swelling capacity measurements, potentiometric and conductivity analysis, and in vitro tests in four liquids: distilled water, Ringer's fluid, artificial saliva, and simulated body fluid (SBF). The incubation results demonstrated the successful formation of new layers of apatite as a result of the interaction with the fluids. Additionally, the influence of the materials on the metabolic activity according to ISO 10993-5:2009 was evaluated by identifying direct contact cytotoxicity towards L-929 mouse fibroblasts, which served as a reference. Moreover, the stimulation of monocytes by hydrogels via the induction of nuclear factor (NF)-κB was investigated. The WPI/HAp composite hydrogels presented in this study therefore show great potential for use as novel bone substitutes.

Synthesis and Characterization of Polymer-Based Coatings Modified with Bioactive Ceramic and Bovine Serum Albumin.

This study involves the synthesis of hydroxyapatite and describes the preparation and characterization of polymer coatings based on poly(ethylene glycol) diacrylate and poly(ethylene glycol) and modified with bovine serum albumin and hydroxyapatite. Hydroxyapatite was obtained by wet chemical synthesis and characterized by X-ray diffraction and FTIR spectroscopy, and its Ca/P molar ratio was determined (1.69 ± 0.08). The ceramic and bovine serum albumin were used in the preparation of composite materials with the polymeric matrix. The chemical composition of coatings was characterized with FTIR spectroscopy, and their morphology was recorded with SEM imaging. Moreover, the measurements of surface roughness parameters and stereometric research were performed. The prepared coatings were subjected to in vitro studies in simulated body fluid and artificial saliva. Changes in chemical composition and morphology after immersion were examined with FTIR spectroscopy and SEM imaging. Based on the conducted research, it can be stated that applied modifiers promote the biomineralization process. The roughness analysis confirmed prepared materials were characterized by the micrometer-scale topography. The materials morphology and roughness, and the morphology of the newly formed apatite deposit, were dependent on the type of the used modifier, and the artificial fluid used in in vitro studies.

Review of the Applications of Biomedical Compositions Containing Hydroxyapatite and Collagen Modified by Bioactive Components.

Regenerative medicine is becoming a rapidly evolving technique in today's biomedical progress scenario. Scientists around the world suggest the use of naturally synthesized biomaterials to repair and heal damaged cells. Hydroxyapatite (HAp) has the potential to replace drugs in biomedical engineering and regenerative drugs. HAp is easily biodegradable, biocompatible, and correlated with macromolecules, which facilitates their incorporation into inorganic materials. This review article provides extensive knowledge on HAp and collagen-containing compositions modified with drugs, bioactive components, metals, and selected nanoparticles. Such compositions consisting of HAp and collagen modified with various additives are used in a variety of biomedical applications such as bone tissue engineering, vascular transplantation, cartilage, and other implantable biomedical devices.