Osteoclast-mediated acidic hydrolysis of thermally gelled curdlan component of the bone scaffolds: Is it possible?

Many biomaterials for bone regeneration have recently been produced using thermally gelled curdlan (1,3-ß-d-glucan) as a binder for bioceramics. As the human organism does not produce enzymes having the ability to degrade curdlan, it is not clear what is the fate of curdlan gel after its implantation in the bone. To clarify this point, in this research osteoclasts were cultured on the curdlan gel to show its degradation by acidic hydrolysis. The studies clearly demonstrated microstructural (AFM and SEM imaging) and chemical changes (Raman spectroscopy) on the curdlan surface caused by osteoclast culture. Moreover, degradation test in a cell-free system using HCl solution (pH = 4.5), mimicking environment in the resorption lacuna, showed great weight loss of the sample, release of glucose, and chemical changes typical of curdlan degradation. Thus, the presented research for the first time provides a strong evidence of osteoclast-mediated acidic hydrolysis of thermally obtained curdlan gel.Peer ReviewedPostprint (published version

Multifunctional Silver(I) Complexes with Metronidazole Drug Reveal Antimicrobial Properties and Antitumor Activity against Human Hepatoma and Colorectal Adenocarcinoma Cells

Silver salts and azole derivatives are well known for their antimicrobial properties. Recent evidence has demonstrated also their cytotoxic and genotoxic potential toward both normal and cancer cells. Still, little is known about the action of complexes of azoles with silver(I) salts. Thus, the goal of the study was to compare the chemical, cytotoxic and antimicrobial properties of metronidazole complexes with silver(I) nitrate and silver(I) sulfate to metronidazole and pure silver(I) salts. We synthetized a novel complex, [Ag(MTZ)2]2SO4, and confirmed its chemical structure and properties using 1H and 13C NMR spectroscopy and X-Ray, IR and elemental analysis. To establish the stability of complexes [Ag(MTZ)2NO3] and [Ag(MTZ)2]2SO4, they were exposed to daylight and UV-A rays and were visually assessed. Their cytotoxicity toward human cancer cells (HepG2, Caco-2) and mice normal fibroblasts (Balb/c 3T3 clone A31) was determined by MTT, NRU, TPC and LDH assays. The micro-dilution broth method was used to evaluate their antimicrobial properties against Gram-positive and Gram-negative bacteria. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy. The photo-stability of the complexes was higher than silver(I) salts. In human cancer cells, [Ag(MTZ)2]2SO4 was more cytotoxic than Ag2SO4 and, in turn, AgNO3 was more cytotoxic than [Ag(MTZ)2NO3]. For Balb/c 3T3 cells, Ag2SO4 was more cytotoxic than [Ag(MTZ)2]2SO4, while the cytotoxicity of AgNO3 and [Ag(MTZ)2NO3] was similar. Metronidazole in the tested concentration range was non-cytotoxic for both normal and cancer cells. The complexes showed increased bioactivity against aerobic and facultative anaerobic bacteria when compared to metronidazole. For the majority of the tested bacterial strains, the silver(I) salts and complexes showed a higher antibacterial activity than MTZ; however, some bacterial strains presented the reverse effect. Our results showed that silver(I) complexes present higher photo-stability, cytotoxicity and antimicrobial activity in comparison to MTZ and, to a certain extent, to silver(I) salts

Nanomaterials to aid wound healing and infection control

The management and treatment of infectious bacterial diseases in wound healing have both become significant research areas in the biomedical field. While current treatments show limitations related to toxicity and exposure time, nanotechnology has become a potential alternative to overcome such challenges. The application of different nanomaterials, with a wide range of elemental compositions, morphologies, and features, has become an essential tool in managing wound healing infections. This book chapter shows an updated view of the newest trends in the control and treatment of bacterial proliferation in the wound bed by utilizing various metal- and nonmetal-based nanostructures

Current Trends in Fabrication of Biomaterials for Bone and Cartilage Regeneration: Materials Modifications and Biophysical Stimulations

The aim of engineering of biomaterials is to fabricate implantable biocompatible scaffold that would accelerate regeneration of the tissue and ideally protect the wound against biodevice-related infections, which may cause prolonged inflammation and biomaterial failure. To obtain antimicrobial and highly biocompatible scaffolds promoting cell adhesion and growth, materials scientists are still searching for novel modifications of biomaterials. This review presents current trends in the field of engineering of biomaterials concerning application of various modifications and biophysical stimulation of scaffolds to obtain implants allowing for fast regeneration process of bone and cartilage as well as providing long-lasting antimicrobial protection at the site of injury. The article describes metal ion and plasma modifications of biomaterials as well as post-surgery external stimulations of implants with ultrasound and magnetic field, providing accelerated regeneration process. Finally, the review summarizes recent findings concerning the use of piezoelectric biomaterials in regenerative medicine

Modifications of Wound Dressings with Bioactive Agents to Achieve Improved Pro-Healing Properties

The great variety of wounds and the lack of an effective universal treatment method has resulted in high demand for modern treatment strategies. Traditional approaches are often ineffective on a variety of chronic wounds, such as venous ulcers or the diabetic foot ulcer. There is strong evidence that naturally derived bioactive compounds have pro-healing properties, raising a great interest in their potential use for wound healing. Plant-derived compounds, such as curcumin and essential oils, are widely used to modify materials applied as wound dressings. Moreover, dressing materials are more often enriched with vitamins (e.g., L-ascorbic acid, tocopherol) and drugs (e.g., antibiotics, inhibitors of proteases) to improve the skin healing rate. Biomaterials loaded with the above-mentioned molecules show better biocompatibility and are basically characterized by better biological properties, ensuring faster tissue repair process. The main emphasis of the presented review is put on the novel findings concerning modern pro-healing wound dressings that have contributed to the development of regenerative medicine. The article briefly describes the synthesis and modifications of biomaterials with bioactive compounds (including curcumin, essential oils, vitamins) to improve their pro-healing properties. The paper also summarizes biological effects of the novel wound dressings on the enhancement of skin regeneration. The current review was prepared based on the scientific contributions in the PubMed database (supported with Google Scholar searching) over the past 5 years using relevant keywords. Scientific reports on the modification of biomaterials using curcumin, vitamins, and essential oils were mainly considered

Osteoconductive and Osteoinductive Surface Modifications of Biomaterials for Bone Regeneration: A Concise Review

The main aim of bone tissue engineering is to fabricate highly biocompatible, osteoconductive and/or osteoinductive biomaterials for tissue regeneration. Bone implants should support bone growth at the implantation site via promotion of osteoblast adhesion, proliferation, and formation of bone extracellular matrix. Moreover, a very desired feature of biomaterials for clinical applications is their osteoinductivity, which means the ability of the material to induce osteogenic differentiation of mesenchymal stem cells toward bone-building cells (osteoblasts). Nevertheless, the development of completely biocompatible biomaterials with appropriate physicochemical and mechanical properties poses a great challenge for the researchers. Thus, the current trend in the engineering of biomaterials focuses on the surface modifications to improve biological properties of bone implants. This review presents the most recent findings concerning surface modifications of biomaterials to improve their osteoconductivity and osteoinductivity. The article describes two types of surface modifications: (1) Additive and (2) subtractive, indicating biological effects of the resultant surfaces in vitro and/or in vivo. The review article summarizes known additive modifications, such as plasma treatment, magnetron sputtering, and preparation of inorganic, organic, and composite coatings on the implants. It also presents some common subtractive processes applied for surface modifications of the biomaterials (i.e., acid etching, sand blasting, grit blasting, sand-blasted large-grit acid etched (SLA), anodizing, and laser methods). In summary, the article is an excellent compendium on the surface modifications and development of advanced osteoconductive and/or osteoinductive coatings on biomaterials for bone regeneration