Optimal Biological Properties Research Articles

Reconstruction of the orbitozygomatic framework: State of the art and perspectives

The reconstruction of the whole orbitozygomatic framework (OZF) is complex and can be encountered in cases of congenital midface deformity, after tumor ablative surgery and in severe facial trauma. Nowadays, surgeon has a wide range of available techniques that have continually grown over the past years, optimizing the surgical management and the aesthetical outcomes. Among them, the autologous bone graft (ABG) remains one of the most suitable options : ABG is easy to harvest and has optimal biological properties for bone healing. It can be tailored to the patient anatomy thanks to the recent advances in computer-assisted surgery. However, substantial drawbacks remain such as the early resorption of the non-vascularized graft, the need of a donor site and its potential morbidity. Alloplastic reconstruction is another option that can resolve both the resorption issue and the donor site morbidity. Moreover, the 3D-printing technologies also allows the manufacturing of patient specific implants. However, alloplastic materials have a variable success, especially due to the high risk of infection or exposure. Consequently, regenerative medicine is a promising field that aims to find a procedure without the disadvantages of ABG or alloplastic based reconstructions, but displaying similar or even higher success rate. Indeed, recent tissue engineering strategies have demonstrated encouraging results for bone regeneration using natural or synthetic biomaterials, patient cells and synthetic bioactive substances. The objective of this review is to present the etiologies of OZF defect, the available reconstruction procedures as well as the current state of the research.

Synthesis of Gelatin/Polyacrylamide/Carboxymethyl chitosan triple-network hydrogels and evaluation of their properties for potential biomedical applications

Multiple network hydrogels are the most widely used materials in biomedical applications due to their optimal biological properties and tunable physical characteristics. Herein, we develop an innovative aqueous‐based synthesis of a novel triple-network Gelatin/Polyacrylamide/Carboxymethyl chitosan hydrogel. Triple-network hydrogel was synthesized by combining a physically crosslinked gelatin as the first network and a covalently crosslinked Polyacrylamide and Carboxymethyl chitosan as the second and third networks, respectively. The hydrogels with different amounts of N, Ń methylene bisacrylamide as a crosslinking agent were prepared using thephotopolymerizationtechnique, and their chemical and physical properties were characterized. The FTIR spectral analysis and NMR analysis confirmed gelatin and CMC chemical modification and demonstrated triple-network hydrogel synthesis. Various studies for characterization of the synthesized triple-network hydrogels revealed the tunability of their physical and mechanical properties by changing the crosslinking agent concentration. The synthesized hydrogels exhibited tailor-made porosity, good mechanical strength, high swelling ratio, and high thermal stability. In addition, the results of L929 fibroblast cell viability assays indicated their adequate cell viability and non-toxicity. These findings introduce these hydrogels as promising, great candidates for use in various shapes and an extended range of medical applications such as tissue engineering scaffolds, delivery systems, and wound dressings.

Justification of a synbiotic preparation (“probiotic+prebiotic”) composition for use in veterinary practice

Studies have been carried out to substantiate the preparation’s composition, which includes a complex of probiotic with prebiotic. It was found that the synbiotic basis is hydrolyzed lignin as a prebiotic with a concentration of 0.5 -2.0%, strain L. paracasei with bacterial cells concentration of 48 B CFU/g with high probiotic activity and optimal biological properties, such as high adhesive activity, antagonistic activity against enteropathogenic microorganisms E. coli and S. aureus and acid-forming activity. This preparation is recommended for use in veterinary practice to prevent and treat dysbiosis, increase the natural resistance of pigs' organism.

Nanomedicines for Renal Management: From Imaging to Treatment.

Nanomedicine has benefited from recent advances in chemistry and biomedical engineering to produce nanoscale materials as theranostic agents. Well-designed nanomaterials may present optimal biological properties, influencing circulation, retention, and excretion for imaging and treatment of various diseases. As the understanding of nanomedicine pharmacokinetics expands continuously, efficient renal clearance of nanomedicines can significantly increase the signal-to-background ratio for precision diagnosis and lower potential toxicity for improved treatment. Studies on nanomaterial-kidney interactions have led to many novel findings on the underlying principles of nanomaterial renal clearance, targeting, and accumulation. In return, the optimized nanomedicines confer significant benefits to the detection and treatment of kidney dysfunction.In this Account, we present an overview of recent progress in the development of nanomaterials for kidney theranostics, aiming to speed up translation and expand possible applications. We start by introducing biological structures of the kidney and their influence on renal targeting, retention, and clearance. Several key factors regarding renal accumulation and excretion, including nanomaterial types, sizes, and shapes, surface charges, and chemical modifications, are identified and discussed. Next, we highlight our recent efforts investigating kidney-interacting nanomaterials and introduce representative nanomedicines for imaging and treatment of kidney diseases. Multiple renal-clearable and renal-accumulating nanomedicines were devised for kidney function imaging. By employing renal-clearable nanomedicines, including gold nanoparticles, porphyrin polymers, DNA frameworks, and polyoxometalate clusters, we were able to noninvasively evaluate split renal function in healthy and diseased mice. Further engineering of renal-accumulating nanosystems has shifted attention from renal diagnosis to precision kidney protection. Many biocompatible nanomedicines, such as DNA origami, selenium-doped carbon quantum dots, melanin nanoparticles, and black phosphorus have all played essential roles in diminishing excessive reactive oxygen species for kidney treatment and protection. Finally, we discuss the challenges and perspectives of nanomaterials for renal care, their future clinical translation, and how they may affect the current landscape of clinical practices. We believe that this Account updates our current understanding of nanomaterial-kidney interactions for further design and control of nanomedicines for specific kidney diagnosis and treatment. This timely Account will generate broad interest in integrating nanotechnology and nanomaterial-biological interaction for state-of-the-art theranostics of renal diseases.

Enhancing X-ray Attenuation of 3D Printed Gelatin Methacrylate (GelMA) Hydrogels Utilizing Gold Nanoparticles for Bone Tissue Engineering Applications.

Bone tissue engineering is a rapidly growing field which is currently progressing toward clinical applications. Effective imaging methods for longitudinal studies are critical to evaluating the new bone formation and the fate of the scaffolds. Computed tomography (CT) is a prevailing technique employed to investigate hard tissue scaffolds; however, the CT signal becomes weak in mainly-water containing materials, which hinders the use of CT for hydrogels-based materials. Nevertheless, hydrogels such as gelatin methacrylate (GelMA) are widely used for tissue regeneration due to their optimal biological properties and their ability to induce extracellular matrix formation. To date, gold nanoparticles (AuNPs) have been suggested as promising contrast agents, due to their high X-ray attenuation, biocompatibility, and low toxicity. In this study, the effects of different sizes and concentrations of AuNPs on the mechanical properties and the cytocompatibility of the bulk GelMA-AuNPs scaffolds were evaluated. Furthermore, the enhancement of CT contrast with the cytocompatible size and concentration of AuNPs were investigated. 3D printed GelMA and GelMA-AuNPs scaffolds were obtained and assessed for the osteogenic differentiation of mesenchymal stem cells (MSC). Lastly, 3D printed GelMA and GelMA-AuNPs scaffolds were scanned in a bone defect utilizing µCT as the proof of concept that the GelMA-AuNPs are good candidates for bone tissue engineering with enhanced visibility for µCT imaging.

Biological effects of acid-eroded MTA Repair HP and ProRoot MTA on human periodontal ligament stem cells.

The aim of this study was to analyze the biological effects of MTA Repair HP and ProRoot MTA on human periodontal ligament stem cells (hPDLSCs) after exposure to acidic and neutral environments. Discs of each material (n = 30) were exposed to phosphate buffered saline (pH = 7.4) or butyric acid (pH = 5.2) for 7days, and biological testing was carried out in vitro on hPDLSCs. Cell viability and apoptosis assays were performed using eluates of each root-end filling material. To evaluate cell attachment to the different materials, hPDLSCs were directly seeded onto the material surfaces and analyzed by scanning electron microscopy. The chemical composition of the root-end filling materials was determined by energy-dispersive x-ray and eluates were analyzed by inductively coupled plasma-mass spectrometry. Statistical differences were assessed by ANOVA and Tukey test (p < 0.05). Under an acidic environment, both materials displayed similar ion release abilities, with the increased release of Si and Ca ions. Substantial changes in microstructure were observed for both materials after exposure to acidic pH. In addition, material exposure to an acidic environment showed a similar degree of cell adherence, and, surprisingly, MTA Repair HP exhibited higher cell viability rates at pH 5.2 than ProRoot MTA. Exposure to an acidic environment promoted Si and Ca ion release from ProRoot MTA and MTA Repair HP. Moreover, we observed optimal biological properties of ProRoot MTA and MTA Repair HP in terms of cell viability, cell death, and cell attachment in both environments. These results may suggest that MTA Repair HP and ProRoot exhibited optimal biological properties in terms of cell viability, cell death and cell attachment in acidic environment, being considered as materials for root-end filling and perforations.

Inflammatory response and biomechanical properties of coaxial scaffolds for engineered skin in vitro and post-grafting

Engineered skin (ES) offers many advantages over split-thickness skin autografts for the treatment of burn wounds. However, ES, both in vitro and after grafting, is often significantly weaker, less elastic and more compliant than normal human skin. Biomechanical properties of ES can be tuned in vitro using electrospun co-axial (CoA) scaffolds. To explore the potential for coaxial scaffold-based ES use in vivo, two CoA scaffolds were fabricated with bioactive gelatin shells and biodegradable synthetic cores of polylactic acid (PLA) and polycaprolactone (PCL), and compared with gelatin monofilament scaffolds. Fibroblast and macrophage production of inflammatory cytokines interleukin 6 (IL-6) and transforming growth factor β-1 was significantly higher when cultured on PLA and PCL monofilament scaffolds compared to gelatin monofilament scaffolds. The core-shell fiber configuration significantly reduced production of pro-inflammatory cytokines to levels similar to those of gelatin monofilament scaffolds. In vitro, ES mechanical properties were significantly enhanced using CoA scaffolds; however, after grafting CoA- and gelatin-based ES to full-thickness excisional wounds on athymic mice, the in vitro mechanical advantage of CoA grafts was lost. A substantially increased inflammatory response to CoA-based ES was observed, with upregulation of IL-6 expression and a significant M2 macrophage presence. Additionally, expression of matrix metalloproteinase I was upregulated and collagen type I alpha 1 was downregulated in CoA ES two weeks after grafting. These results suggest that while coaxial scaffolds provide the ability to regulate biomechanics in vitro, further investigation of the inflammatory response to core materials is required to optimize this strategy for clinical use. Statement of SignificanceEngineered skin has been used to treat very large burn injuries. Despite its ability to heal these wounds, engineered skin exhibits reduced biomechanical properties making it challenging to manufacture and surgically apply. Coaxial fiber scaffolds have been utilized to tune the mechanical properties of engineered skin while maintaining optimal biological properties but it is not known how these perform on a patient especially with regards to their inflammatory response. The current study examines the biomechanical and inflammatory properties of coaxial scaffolds and uniaxial scaffolds in vitro and in vivo. The results show that the biological response to the scaffold materials is a critical determinant of tissue properties after grafting with reduced inflammation and rapid scaffold remodeling leading to stronger skin.

Structural Studies and Gene Silencing Activity of siRNAs Containing Cationic Phosphoramidate Linkages.

A series of siRNA duplexes containing cationic non-bridging 3',5'-linked phosphoramidate (PN) linkages was designed and synthesized using a combination of phosphoramidite and H-phosphonate chemistries. Modified oligonucleotides were assayed for their thermal stability, helical structure, and ability to modulate the expression of firefly luciferase. We demonstrate that PN modifications of siRNAs are, in general, minimally destabilizing with respect to duplex thermal stability; destabilization can be mitigated through the incorporation of 2'-modified RNA-like residues or PN conjugates containing ionizable pendant moieties. We also demonstrate that single cationic dimethylethylenediamine PN linkages have little effect on siRNA potency, whether located in the passenger or guide strand of the duplex. Highly modified siRNA passenger strands were further modified with up to four cationic PN linkages, with little effect on duplex potency or helical structure. We envision that PN modifications could be useful in the production of therapeutic siRNAs with optimal biological properties.

A review of decellurization methods caused by an urgent need for quality control of cell-free extracellular matrix' scaffolds and their role in regenerative medicine.

The natural extracellular matrix (ECM),thanks to its specific properties (e.g., collagenous lattice, a reservoir of growth factors, ECM-cell anchoring areas, an optimal pH and CO2 ),ensures an optimal microenvironment for homeostatic and regenerative cell development. In the context of regenerative medicine, ECM is a lair for residual and infiltrative cells. The aim of the clinical usage of cell-free ECM scaffolds is the enhancement of tissue regeneration with possible minimization of an adverse host reaction on allogeneic or xenogeneic biomaterial. Thus, the objective of decellularization is to obtain acellular grafts characterized by optimal biological properties, such as a lack of remaining cellular elements (e.g., cell membrane phospholipids and proteins, nucleic acids, mitochondria), lack of immunogenicity, lack of calcification promotion and lack of cytotoxicity (e.g., in unrinsed detergents). Furthermore, cell-free ECM scaffolds should present the optimal mechanical and structural properties that may ensure the biocompatibility of the graft. The maintenance of the ultrastructure composition of the ECM is one of the most important goals of decellularization. All physical, chemical, and biological methods proposed (used separately or in combination to extract cells from tissues/organs) are not 100% effective in cell removal and always cause a disruption of the ECM texture, as well as a probable loss of important structure components. Although cell-free ECM scaffolds are generally classified as medical devices, there are no widely accepted or legally defined criteria for quality control/evaluation methods of obtained matrices. Such criteria must be provided. Some of them have been proposed in this manuscript. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 909-923, 2018.

Development and evaluation of degradable hydroxyapatite/sodium silicate composite for low-dose drug delivery systems

This study was designed to develop innovative degradable hydroxyapatite (HAp)-based systems working as potential carriers for low-dose drugs. The HAp-based systems combine three components: HAp, sodium silicate and citric acid (HSC), which together could exhibit optimal characteristics as drug carriers. Both synthetic HAp (s-HAp) and extracted biological HAp (b-HAp) were used as sources of HAp due to their optimal biological properties and adsorption capacity. The s-HAp powder was prepared by co-precipitation method, while the b-HAp powder was extracted from bovine bone. Aqueous drug solutions of the atenolol, antihypertensive drug, were used as a model drug to investigate the drug release behaviour from HSC composites. The properties of s-HAP, b-HAp powders and HSC composite tablets were characterized by conventional methods. The results revealed that both s-HAp and b-HAp are pure powders and exhibited agglomerated microstructures with grain sizes less than 100 μm. The HSC composite tablets exhibited a dense structure, excellent compressive strength and excellent in-vitro release behaviour of atenolol. The results indicated that HAp powders and their composite tablets can be promised as economic raw materials and carriers for low-dose drugs.

ELECTROKINETIC PROPERTIES, IN VITRO DISSOLUTION, AND PROSPECTIVE HEMOAND BIOCOMPATIBILITY OF TITANIUM OXIDE AND OXYNITRIDE FILMS FOR CARDIOVASCULAR STENTS

A state of titanium oxide and oxynitride coatings on L316 steel has been studied before and after their contact with model biological fluids. Electrokinetic investigation in 1 mmol potassium chloride showed significant (more than 10 times) fall of magnitude of electrostatic potential of thin (200–300 nm) titanium films at pH changing in the range of 5–9 units during 2 h. Nevertheless, zeta-potential of all samples had negative charge under pH &gt; 6.5. Long-term (5 weeks) contact of samples with simulated body fluid (SBF) promoted steel corrosion and titanium oxide and oxynitride films dissolution. On the other hand, sodium and chloride ions precipitation and sodium chloride crystals formation occurred on the samples. Of positive fact is an absence of calcification of tested artificial surfaces in conditions of long-term being in SBF solution. It is supposed decreasing hazard of fast thrombosis and loss of materials functional properties. According to in vitro experiment conducted, prospective biocompatibility of materials tested before and after their contact with SBF lines up following manner: Ti–O–N (1/3) &gt; Ti–O–N (1/1), TiO2 &gt; Steel. It may be explained by: 1) the corrosion-preventive properties of thin titanium oxide and oxynitride films;2) a store of surface negative charge for Ti–O–N (1/3) film; 3) minor augmentation of mass and thickness of titanium films connected with speed of mineralization processes on the interface of solution/solid body. At the same time, initial (before SBF contact) differences of samples wettability became equal. Modifying effect of model biological fluids on physicochemical characteristics of materials tested (roughness enhancement, a reduction or reversion of surface negative potential, sharp augmentation of surface hydrofilicity) should took into account under titanium oxide and oxynitride films formation and a forecast of their optimal biological properties as the materials for cardiovascular stents.

Poly-ε-caprolactone composite scaffolds for bone repair.

Synthetic biomaterials combined with cells and osteogenic factors represent a promising approach for the treatment of a number of orthopedic diseases, such as bone trauma and congenital malformations. To guarantee optimal biological properties, bone substitutes are prepared with a 3D structure and porosity grade functional to drive cell migration and proliferation, diffusion of factors, vascularization and cell waste expulsion. In this study, synthetic hydroxyapatite (HA) or rat bone extracellular matrix (BP) were examined in an effort to optimize the mechanical properties and osteogenic activity of poly-ε-caprolactone scaffolds prepared with alginate threads (PCL-AT). Using rabbit bone marrow-derived mesenchymal stem cells (rMSCs), the effects of PCL composite substrates on cell adhesion, growth and osteogenic differentiation were evaluated. Micro-CT analysis and scanning electron microscopy evidenced that porous PCL scaffolds containing HA or BP acquire a trabecular bone-like structure with interconnected pores homogenously distributed and are characterized by a pore diameter of approximately 10 µm (PCL-AT-BP) or ranging from 10 to 100 µm. Although the porosity grade of both PCL-AT-HA and PCL-AT-BP promoted optimal conditions for the cell growth of rMSCs at the early phase, the presence of BP was crucial to prolong the cell viability at the late phase. Moreover, a precocious expression of Runx2 (at 7 days) was observed in PCL-AT-BP in combination with osteogenic soluble factors suggesting that BP controls better than HA the osteogenic maturation process in bone substitutes.

IMMUNOMODULATORY ACTIVITY OF ANTIMICROBIAL PEPTIDE INDOLICIDIN AND ITS STRUCTURAL ANALOGUES

Immunomodulatory activity of a native antimicrobial peptide indolicidin and its synthetic structural analogues (indolicidin 7, 8,20,21,22), with spatial uncoupling of hydrophobic and hydrophilic parts of the molecule and different net charges was under investigation. It was revealed that indolicidin 7 and 22 at concentrations of, respectively, 0.6 uM and 5 uM suppressed cytotoxic activity of natural killer spleen cells against tumor cells (K-562 line), while indolicidins 8,20 and 21 at the concentrations of 1.3 uM, 2.5 uM and 5 uM respectively, did not influence it. It was shown for the first time, that native indolicidin and its structural analogues indolicidin 8 and 20 did not increase activity of cell division, whereas indolicidin 7 and 22 had a direct mitogenic activity on spleen cells. The investigated peptides showed inhibitory effect upon mitogenic transformation of splenocytes induced by Con A. In addition, indolicidin and its structural analogues suppressed co-mitogenic activity of Interleikin-1 towards splenocytes. The results obtained allow of a conclusion that the structural changes of indolicidin molecule lead to emergence of novel immunomodulatory activities of the peptides, whereas the methods of structural modifications demonstrate potential approaches to directed design of molecules with optimal biological properties.

The role of silicon in osteoblast-like cell proliferation and apoptosis

The optimal concentration at which Si induces cell functions has not been fully elucidated. In the present study the effects of Si concentration (0–6 mM) on the biological functions of MG63 cells were investigated. Cell proliferation in the presence of 2 mM Si- and 4 mM Si-containing media progressively increased with culture time, whereas that of 6 mM Si treated MG63 cells was significantly ( P < 0.05) reduced. The unusually high Si concentration (6 mM) induced a significant ( P < 0.05) increase in the sub-G1 phase of cells from the original 3.60% up to 43.01% after culture for 12 h. In contrast, the other lower Si concentration treated MG63 cells in the sub-G1 phase were in the range 3–5% at all culture time points. 4 mM Si treated MG63 cells, but not 6 mM Si treated MG63 cells, showed remarkably enhanced collagen type I (COL I) gene expression and extracellular signal-regulated kinase (ERK) secretion, which were significantly ( P < 0.05) higher than those in the control medium. The activation of ERK was also stimulated in MG63 cells by 4 mM Si. Cells cultured in the presence of 4 mM Si were found to have calcium matrix formation on day 7 that was 15-fold greater than that in the control medium. The results obtained in this study may be useful in designing calcium silicate-based materials with optimal biological properties.

Conditions for radioiodination of antithrombin III retaining its biological properties

In order to obtain a radioiodinated antithrombin III (AT III) with a good labelling yield and optimal biological properties towards heparin, thrombin and its anti-AT III monoclonal antibodies, we compared the classical labelling methods and found them wanting. Thus, we perfected a new labelling procedure which fulfils the above requirements.