Although selenium nanoparticles (SeNPs) have gained attention in the scientific community mostly through investigation of their anticancer activity, a great potential of this nanomaterial was recognized recently regarding its antimicrobial activity. The particle form, size, and surface chemistry have been recognized as crucial parameters determining the interaction of nanomaterials with biological entities. Furthermore, considering a narrow boundary between beneficial and toxic effects for selenium per se, it is clear that investigations of biomedical applications of SeNPs are very demanding and must be done with great precautions. The goal of this work is to evaluate the effects of SeNPs surface chemistry and structure on antimicrobial activity against several common bacterial strains, including Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 6633), and Kocuria rhizophila (ATCC 9341), as well as Escherichia coli (ATCC 8739), Salmonella Abony (NCTC 6017), Klebsiella pneumoniae (NCIMB 9111) and Pseudomonas aeruginosa (ATCC 9027), and the standard yeast strain Candida albicans (ATCC 10231). Three types of SeNPs were synthesized by chemical reduction approach using different stabilizers and reducing agents: (i) bovine serum albumin (BSA) + ascorbic acid, (ii) chitosan + ascorbic acid, and (iii) with glucose. A thorough physicochemical characterization of the obtained SeNPs was performed to determine the effects of varying synthesis parameters on their morphology, size, structure, and surface chemistry. All SeNPs were amorphous, with spherical morphology and size in the range 70–300 nm. However, the SeNPs obtained under different synthesis conditions, i.e. by using different stabilizers as well as reducing agents, exhibited different antimicrobial activity as well as cytotoxicity which are crucial for their applications. In this paper, the antimicrobial screening of the selected systems is presented, which was determined by the broth microdilution method, and inhibitory influence on the production of monomicrobial and dual-species biofilm was evaluated. The potential mechanism of action of different systems is proposed. Additionally, the cytotoxicity of SeNPs was examined on the MRC-5 cell line, in the same concentration interval as for antimicrobial testing. It was shown that formulation SeNPs-BSA expressed a significantly lower cytotoxic effect than the other two formulations.

Since the early 2000s, borate bioactive glasses (BBGs) have been extensively investigated for biomedical applications. The research so far indicates that BBGs frequently exhibit superior bioactivity and bone healing capacity compared to silicate glasses. They are also suitable candidates as drug delivery devices for infection or disease treatment such as osteoporosis. Additionally, BBGs are also an excellent option for wound healing applications, which includes the availability of commercial (FDA approved) microfibrous BBG dressings to treat chronic wounds. By addition of modifying ions, the bone or wound healing capacity of BBGs can be enhanced. For instance, addition of copper ions into BBGs was shown to drastically increase blood vessel formation for wound healing applications. Moreover, addition of ions such as magnesium, strontium, and cobalt improves bone healing. Other recent research interest related to BBGs is focused on nerve and muscle regeneration applications, while cartilage regeneration is also suggested as a potential application field for BBGs. BBGs are commonly produced by melt-quenching; however, sol-gel processing of BBGs is emerging and appears to be a promising alternative. In this review paper, the physical and biological characteristics of BBGs are analyzed based on the available literature, the applications of BBGs are discussed, and future research directions are suggested.

The regulatory functions of the immune response in tissue healing, repair, and regeneration have been evidenced in the last decade. Immune cells play central roles in immune responses toward inducing favorable tissue regenerative processes. Modulating and controlling the immune cell responses (particularly macrophages) is an emerging approach to enhance tissue regeneration. Bioactive glasses (BGs) are multifunctional materials exhibiting osteogenic, angiogenic, and antibacterial properties, being increasingly investigated for various tissue regeneration scenarios, including bone regeneration and wound healing. On the other hand, the immunomodulatory effects of BGs in relation to regenerating tissues have started to be understood, and key knowledge is emerging. This is the first review article summarizing the immunomodulatory effects of BGs for tissue repair and regeneration. The immune response to BGs is firstly introduced, discussing potential mechanisms regarding the immunomodulation effects induced by BGs. Moreover, the interactions between the immune cells involved in the immunomodulation process and BGs (dissolution products) are summarized in detail. Particularly, a well-regulated and timely switch of macrophage phenotype from pro-inflammatory to anti-inflammatory is crucial to constructive tissue regeneration through modulating osteogenesis, osteoclastogenesis, and angiogenesis. The influence of BG characteristics on macrophage responses is discussed. We highlight the strategies employed to harness macrophage responses for enhanced tissue regeneration, including the incorporation of active ions, surface functionalization, and controlled release of immunomodulatory molecules. Finally, we conclude with our perspectives on future research challenges and directions in the emerging field of immunomodulatory BGs for tissue regeneration. STATEMENT OF SIGNIFICANCE: Immunomodulatory effects of bioactive glasses (BGs) in relation to bone regeneration and wound healing have started to be understood. We summarize those studies which have focused on immunomodulatory BGs for tissue regeneration. We first introduce the potential mechanisms of the immunomodulation effects induced by BGs. Interactions between the cells involved in immunomodulation processes and BGs (and their dissolution products, biologically active ions) are elaborated. We highlight the strategies employed to modulate macrophage responses for enhancing tissue regeneration, including incorporation of active ions, surface functionalization, and controlled release of immunomodulatory agents. This is the first review article summarizing and outlining the immunomodulatory effects of BGs for tissue regeneration. We anticipate that increasing research efforts will start to emerge in the area of immunomodulatory BGs.

Mesoporous silica-based materials, especially mesoporous bioactive glasses (MBGs), are being highly considered for biomedical applications, including drug delivery and tissue engineering, not only because of their bioactivity and biocompatibility but also due to their tunable composition and potential use as drug delivery carriers owing to their controllable nanoporous structure. Numerous researches have reported that MBGs can be doped with various therapeutic ions (strontium, copper, magnesium, zinc, lithium, silver, etc.) and loaded with specific biomolecules (e.g., therapeutic drugs, antibiotics, growth factors) achieving controllable loading and release kinetics. Therefore, co-delivery of ions and biomolecules using a single MBG carrier is highly interesting as this approach provides synergistic effects toward improved therapeutic outcomes in comparison to the strategy of sole drug or ion delivery. In this review, we discuss the state-of-the-art in the field of mesoporous silica-based materials used for co-delivery of ions and therapeutic drugs with osteogenesis/cementogenesis, angiogenesis, antibacterial and anticancer properties. The analysis of the literature reveals that specially designed mesoporous nanocarriers can release multiple ions and drugs at therapeutically safe and relevant levels, achieving the desired biological effects (in vivo, in vitro) for specific biomedical applications. It is expected that this review on the ion/drug co-delivery concept using MBG carriers will shed light on the advantages of such co-delivery systems for clinical use. Areas for future research directions are identified and discussed.