Engineering of a Biomimetic Interface between a Native Dental Tissue and Restorative Composite and Its Study Using Synchrotron FTIR Microscopic Mapping

The aim of this work is to develop a biomimetic interface between the natural tooth tissue and the restorative composite and to study it on the basis of synchrotron micro-FTIR mapping and multidimensional processing of the spectral data array. Using hierarchical cluster analysis of 3D FTIR data revealed marked improvements in the formation of the dentine/adhesive/dental hybrid interface using a biomimetic approach. The use of a biomimetic strategy (application of an amino acid–modified primer, alkaline calcium and a nano-c-HAp–modified adhesive) allowed the formation of a matrix that can be structurally integrated with natural dentine and dental composite. The biomimetic hybrid layer was characterised by homogeneous chemical composition and a higher degree of conversion of the adhesive during polymerisation, which should provide optimal integration of the dental composite with the dentine.     

Systematic Review: Adipose-Derived Mesenchymal Stem Cells,Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors’ experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.     

Current Knowledge in Skin Metabolomics: Updates from Literature Review

Metabolomic profiling is an emerging field consisting of the measurement of metabolites in a biological system. Since metabolites can vary in relation to different stimuli, specific metabolic patterns can be closely related to a pathological process. In the dermatological setting, skin metabolomics can provide useful biomarkers for the diagnosis, prognosis, and therapy of cutaneous disorders. The main goal of the present review is to present a comprehensive overview of the published studies in skin metabolomics. A search for journal articles focused on skin metabolomics was conducted on the MEDLINE, EMBASE, Cochrane, and Scopus electronic databases. Only research articles with electronically available English full text were taken into consideration. Studies specifically focused on cutaneous microbiomes were also excluded from the present search. A total of 97 papers matched all the research criteria and were therefore considered for the present work. Most of the publications were focused on inflammatory dermatoses and immune-mediated cutaneous disorders. Skin oncology also turned out to be a relevant field in metabolomic research. Only a few papers were focused on infectious diseases and rarer genetic disorders. All the major metabolomic alterations published so far in the dermatological setting are described extensively in this review.     

Effect of solvents on inhibition of collagen-bound proteases by chlorhexidine

Chlorhexidine (CHX) incorporation during dentine bonding with dental adhesives enhances bond durability. Choosing an appropriate solvent for CHX to enhance resin–dentine bond durability is important. This study was conducted to examine the effect of solvents on the inhibition of dentine collagen-bound proteases by chlorhexidine. The inhibitory effects of CHX (0.2% and 2%) incorporated in three different solvents (water/ethanol/acetone) on the inhibition of dentine matrix-bound proteases were investigated by assessing the change in dry mass of demineralized dentine beams and the release of solubilized collagen peptides after 30 days. Solvents without CHX were used as controls. The beams treated with 2% CHX exhibited significantly lesser loss of dry mass and hydroxyproline release when incorporated in ethanol than in water (p<0.05). No significant difference in the inhibitory effect on dentine matrix-bound proteases was found between 0.2% and 2% CHX (p>0.05). The incorporation of 2% chlorhexidine in ethanol showed greater inhibitory effect on dentine matrix-bound proteases than in water.     

Preparation of CaCO3‐based biomineralized polyvinylpyrrolidone–carboxymethylcellulose hydrogels and their viscoelastic behavior

In the blend of natural and synthetic polymer‐based biomaterial of polyvinylpyrrolidone (PVP) and carboxymethylcellulose (CMC), fabrication of CaCO₃ was successfully accomplished using simple liquid diffusion technique. The present study emphasizes the biomimetic mineralization in PVP–CMC hydrogel, and furthermore, several properties of this regenerated and functionalized hydrogel membranes were investigated. The physical properties were studied and confirmed the presence of CaCO₃ mineral in hydrogel by Fourier transform infrared spectroscopy and Scanning electron microscopy. Moreover, the absorptivity of water and mineral by PVP–CMC hydrogel was studied to determine its absorption capacity. Further, the viscoelastic properties (storage modulus, loss modulus, and complex viscosity) of mineralized and swelled samples (time: 5–150 min) were measured against angular frequency. It is interesting to know the increase of elastic nature of mineralized hydrogel filled with CaCO₃ maintaining the correlation between elastic property and viscous one of pure hydrogel. All these properties of biomineralized hydrogel suggest its application in biomedical field, like bone treatment, bone tissue regeneration, dental plaque and tissue replacement, etc. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40237.     

Biomimetic chitosan-hydroxyapatite hybrid biocoatings for enamel remineralization

Development of biomimetic ceramic-based materials is currently a challenge in dental tissue engineering. Synthetic hybrid chitosan (CS)-hydroxyapatite (HAP) layers are regarded as candidates for teeth remineralization, protection against further demineralization ensuring also antibacterial activity. Thus, the aim of this work was to obtain new biomimetic CS-HAP layers for restoration of damaged mature enamels and to pursue morphological, compositional, structural and hardness modifications of the grown layers by immersion for 4, 7 and 10 days into artificial saliva (AS) under CS-Emdogain (EMD) hydrogel action. SEM-EDX, HRTEM-SAED, FTIR and micro-Raman findings indicated formation of carbonate-substituted HAP, B-type, with c-axis orientation in the newly formed CS-HAP coatings. Prolonged immersion span of 10 days caused increasing CS content in the superficial grown layer while carbonate content diminished. Optimum Ca/P ratio (1.85 at%) and hardness of 2.48 GPa were recorded for seven days growth using CS-EMD hydrogel. Subtle changes in HAP lattice parameters were recorded for 10-day grown layer while c-axis orientation of HAP crystals at mesoscale was preserved. Mechanism of CS interaction during in situ biomimetic synthesis and self-assembly of HAP crystals under CS-EMD hydrogel presence is also discussed.     

Bio-Morphological Reaction of Human Periodontal Ligament Fibroblasts to Different Types of Dentinal Derivates: In Vitro Study

Understanding the biological and morphological reactions of human cells towards different dentinal derivate grafting materials is fundamental for choosing the type of dentin for specific clinical situations. This study aimed to evaluate human periodontal ligament fibroblasts (hPLF) cells exposed to different dentinal derivates particles. The study design included the in vitro evaluation of mineralized dentine (SG), deproteinized and demineralized dentine (DDP), and demineralized dentine (TT) as test materials and of deproteinized bovine bone (BIOS) as the positive control material. The materials were kept with the hPLF cell line, and the evaluations were made after 24 h, 72 h, and 7 days of in vitro culture. The evaluated outcomes were proliferation by using XTT assays, the morphological characteristics by light microscopy (LM) and by the use of scanning electron microscopy (SEM), and adhesion by using confocal microscopy (CLSM). Overall, the experimental materials induced a positive response of the hPLFs in terms of proliferation and adhesion. The XTT assay showed the TT, and the SG induced significant growth compared to the negative control at 7 days follow-up. The morphological data supported the XTT assay: the LM observations showed the presence of densely packed cells with a modified shape; the SEM observations allowed the assessment of how fibroblasts exposed to DDP and TT presented cytoplasmatic extensions; and SG and BIOS also presented the thickening of the cellular membrane. The CLMS observations showed the expression of the proliferative marker, as well as and the expression of cytoskeletal elements involved in the adhesion process. In particular, the vinculin and integrin signals were stronger at 72 h, while the actin signal remained constantly expressed in all the follow-up of the sample exposed to SG material. The integrin signal was stronger at 72 h, and the vinculin and actin signals were stronger at 7 days follow-up in the sample exposed to DDP material. The vinculin and integrin signals were stronger at 72 h follow-up in the sample exposed to TT material; vinculin and integrin signals appear stronger at 24 h follow-up in the sample exposed to BIOS material. These data confirmed how dentinal derivates present satisfying biocompatibility and high conductivity and inductivity properties fundamental in the regenerative processes. Furthermore, the knowledge of the effects of the dentin’s degree of mineralization on cellular behavior will help clinicians choose the type of dentine derivates material according to the required clinical situation.     

Bonding of adhesive resin to intraradicular dentine: A review of the literature

Bonding to intraradicular dentine is widely practiced by modern dentists, both in general as well as specialist practices. Materials, such as resin-based root canal sealers and resin cements, are routinely used in endodontic treatment, like root canal obturation and luting fiber post for post and core restorations. Though bonding to intraradicular dentine in principle is the same as bonding to coronal dentine, there are several structural differences between coronal and intraradicular dentine substrates. Also, the consequences of pulpal necrosis and subsequent endodontic therapy could alter the intraradicular dentine substrate significantly, which would have an impact on intraradicular dentine bonding. Therefore, this comprehensive review was performed from the published literature retrieved from “Pubmed” database using specific keywords “root, “dentine”, “resin”, and “bonding”. The relevant articles were selected after screening the title and abstracts. Further relevant articles included in this review were identified from the reference lists of the originally retrieved articles. In this review, we have narrated the various aspects of bonding to intraradicular root dentine. Successful bonding to intraradicular dentine depends on proper understanding of this unique bonding substrate.     

Synthesis of Antibacterial Hybrid Hydroxyapatite/Collagen/Polysaccharide Bioactive Membranes and Their Effect on Osteoblast Culture

Inspired by the composition and confined environment provided by collagen fibrils during bone formation, this study aimed to compare two different strategies to synthesize bioactive hybrid membranes and to assess the role the organic matrix plays as physical confinement during mineral phase deposition. The hybrid membranes were prepared by (1) incorporating calcium phosphate in a biopolymeric membrane for in situ hydroxyapatite (HAp) precipitation in the interstices of the biopolymeric membrane as a confined environment (Methodology 1) or (2) adding synthetic HAp nanoparticles (SHAp) to the freshly prepared biopolymeric membrane (Methodology 2). The biopolymeric membranes were based on hydrolyzed collagen (HC) and chitosan (Cht) or κ-carrageenan (κ-carr). The hybrid membranes presented homogeneous and continuous dispersion of the mineral particles embedded in the biopolymeric membrane interstices and enhanced mechanical properties. The importance of the confined spaces in biomineralization was confirmed by controlled biomimetic HAp precipitation via Methodology 1. HAp precipitation after immersion in simulated body fluid attested that the hybrid membranes were bioactive. Hybrid membranes containing Cht were not toxic to the osteoblasts. Hybrid membranes added with silver nanoparticles (AgNPs) displayed antibacterial action against different clinically important pathogenic microorganisms. Overall, these results open simple and promising pathways to develop a new generation of bioactive hybrid membranes with controllable degradation rates and antimicrobial properties.     

Calcium phosphate and calcium carbonate mineralization of bioinspired hydrogels based on β-chitin isolated from biomineral of the common cuttlefish (<Emphasis Type="Italic">Sepia officinalis</Emphasis>, L.)

Chitin, a bioactive, antibacterial and biodegradable polymer is commonly utilized by diverse marine organisms as the main scaffold material during biomineralization. Due to its properties, chitin is also of interest as a component of organo-inorganic composites for diverse biomedical applications. In this study, chitinous fibers isolated from the cuttlebone of the common cuttlefish (Sepia officinalis, L.) are characterized and evaluated for use as an integral part of mineralized hydrogels for biomedical applications. Since marine organisms use calcium carbonates (CaCO₃), while vertebrates use calcium phosphates (CaP) as the main inorganic hard tissue components, and both minerals are used in hard tissue engineering, they were compared to determine which composite is potentially a better biomaterial. Hydrogel mineralization was conducted by subsequent dipping into cationic and anionic reactant solutions, resulting in the formation of a CaCO₃ or CaP coating that penetrated into the hydrogel. Obtained composites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), rheology, swelling tests and simple compression. The results indicate that β-chitin can be used for the preparation of moldable hydrogels that are easily mineralized. Mineralized hydrogels have higher elasticity than non-mineralized ones while swelling is better if the extent of mineralization is lower. Further optimization of the hydrogels composition could improve their stress response and Young’s modulus, where the current hydrogel with a higher extent of CaP mineralization excels in comparison to all other investigated composites.     

Preparation of genipin‐fixed agarose hydrogel

Genipin, a naturally occurring crosslinker, was employed to modify agarose in aqueous medium at pH ～ 7 at ambient conditions. The physical and rheological properties were studied. The genipin‐fixed agarose hydrogel (0.8 wt % genipin with respect to the polysaccharide) having the maximum swelling capacity was obtained after 85‐h crosslinking reaction. The reaction mixture developed a dark blue color with the passage of time, indicating thereby the progress of the crosslinking reaction in presence of genipin. The maximum swelling of the genipin‐fixed agarose hydrogel in acidic medium at pH 1.2 was ～ 48 g/g, whereas the parent polysaccharide agarose achieved equilibrium swelling state at 6 g/g. The genipin‐fixed agarose showed 30% weight loss in Ringer's solution, while the agarose polysaccharide exhibited ～ 50% weight loss in the same medium, both after 60 days. The thermogravimetric analysis studies revealed enhanced thermal stability of the genipin‐fixed agarose hydrogel. In view of the enhanced stability and swelling capacity of the genipin‐fixed agarose compared to agarose, the value added polysaccharide may be useful in new applications as super absorbents and in biomedical applications. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 290–296, 2007     

Polymers used to influence cell fate in 3D geometry: New trends

The extracellular matrix (ECM) is a hydrogel-like structure comprised of several different biopolymers, encompassing a wide range of biological, chemical, and mechanical properties. The composition, organization, and assembly of the ECM play a critical role in cell function. Cellular behavior is guided by interactions that occur between cells and their local microenvironment, and this interrelationship plays a significant role in determining physiological functions. Bioengineering approaches have been developed to mimic native tissue microenvironments by fabricating novel bioactive hydrogel scaffolds. This review explores material designs and fabrication approaches that are guiding the design of hydrogels as tissue engineered scaffolds. As the fundamental biology of the cellular microenvironment is often the inspiration for material design, the review focuses on modifications to control bioactive cues such as adhesion molecules and growth factors, and summarizes the current applications of biomimetic scaffolds that have been used in vitro as well as in vivo.     

Chemical synthesis of biomimetic hydrogels for tissue engineering

Owing to their high water content, porous structure, biocompatibility and tissue‐like viscoelasticity, hydrogels have become attractive and promising biomaterials for use in drug delivery, three‐dimensional cell culture and tissue engineering applications. Various chemical approaches have been developed for hydrogel synthesis using monomers or polymers carrying reactive functional groups. For in vivo tissue repair and in vitro cell culture purposes, it is desirable that the crosslinking reactions occur under mild conditions, do not interfere with biological processes and proceed at high yield with exceptional selectivity. Additionally, the crosslinking reaction should allow straightforward incorporation of bioactive motifs or signaling molecules, at the same time providing tunability of the hydrogel microstructure, mechanical properties and degradation rates. In this review, we discuss various chemical approaches applied to the synthesis of complex hydrogel networks, highlighting recent developments from our group. The discovery of new chemistries and novel materials fabrication methods will lead to the development of the next generation of biomimetic hydrogels with complex structures and diverse functionalities. These materials will likely facilitate the construction of engineered tissue models that may bridge the gap between two‐dimensional experiments and animal studies, providing preliminary insight prior to in vivo assessments. © 2017 Society of Chemical Industry     

Yicathins B and C and Analogues: Total Synthesis,Lipophilicity and Biological Activities

Natural products have always been an important source of new hits and leads in drug discovery, with the marine environment being regarded as a significant source of novel and exquisite bioactive compounds. Yicathins B and C are two marine-derived xanthones that have shown antibacterial and antifungal activity. Herein, the total synthesis of these yicathins and six novel analogues is reported for the first time. As marine natural products tend to have very lipophilic scaffolds, the lipophilicity of yicathins and their analogues was evaluated in the classical octanol/water system and a biomimetic model-based system. As the xanthonic nucleus is a “privileged structure”, other biological activities were evaluated, namely antitumor and anti-inflammatory activities. An interesting anti-inflammatory activity was identified for yicathin analogues that paves the way for the design of dual activity (anti-infective and anti-inflammatory) marine-inspired xanthone derivatives.     

The Effect of Carbon Nanotubes added into Bullfrog Collagen Hydrogel on Gentamicin Sulphate Release: In Vitro

We demonstrate the preparation and its drug delivery behavior of this novel hybrid collagen-carbon nanotubes (CNTs) hydrogel obtained. CNTs can be taken as an additive to enhance the stability of the hybrid hydrogel. As a result, the sustained release effects of the hybrid hydrogel on gentamicin sulphate were significantly improved. The hybrid hydrogel combined the excellent safety of bullfrog collagen and the enhanced stability of CNTs brought to the hybrid hydrogel. It suggests that the hybrid collagen hydrogel with CNTs could be used as a novel kind of drug delivery matrix.     

Biomineralized hyaluronic acid/poly(vinylphosphonic acid) hydrogel for bone tissue regeneration

Novel biomineralized hydrogels composed of hyaluronic acid (HA) and vinyl phosphonic acid (VPAc) were designed with the aim of developing a biomimetic hydrogel system to improve bone regeneration by local delivery of a protein drug including bone morphogenetic proteins. We synthesized crosslinked hydrogels composed of methacrylated HA and poly(VPAc) [P(VPAc)], which serves as a binding site for calcium ions during the mineralization process. The HA/P(VPAc) hydrogels were biomineralized by a urea‐mediation method to create functional polymer hydrogels that can deliver the protein drug and mimic the bone extracellular matrix. The water content of the hydrogels was influenced by the HA/P(VPAc) composition, crosslinking density, biomineralization, and ionic strength of the swelling media. All HA/P(VPAc) hydrogels maintained more than 84% water content. Enzymatic degradation of HA/P(VPAc) hydrogels was dependent on the concentration of hyaluronidase and the crosslinking density of the polymer network within the hydrogel. In addition, the release behavior of bovine serum albumin from the HA/PVPAc hydrogels was mainly influenced by the drug loading content, water content, and biomineralization of the hydrogels. In a cytotoxicity study, the HA/P(VPAc) and biomineralized HA/P(VPAc) hydrogels did not significantly affect cell viability. These results suggest that biomineralized HA/P(VPAc) hydrogels can be tailored to create a biomimetic hydrogel system that promotes bone tissue repair and regeneration by local delivery of protein drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41194.     

Optimized production of a high-performance hybrid biomaterial: biomineralized spider silk for bone tissue engineering

Silks have been widely used as biomaterials due to their biocompatibility, biodegradability, and excellent mechanical properties. In the present work, native spider silk was used as organic template for controlled nucleation of hydroxyapatite (HA) nano-coating that can act as biomimetic interface. Different bio-inspired neutralization methods and process parameters were evaluated to optimize the silk functionalization. The morphology and chemical composition were investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis and mechanical properties were studied through tensile tests. Results showed that the optimized protocol enabled a controlled and homogeneous nucleation of apatite nano-crystals while maintaining silk mechanical performances after mineralization. This study reports the optimization of a simple and effective bio-inspired nucleation process for precise nucleation of HA onto spider silk templates, suitable to develop high-performance hybrid interfaces for bone tissue engineering. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48739.     

Hybrid Core-Shell Polymer Scaffold for Bone Tissue Regeneration

A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles. After particle leaching in water, the core was grafted with a gelatin/chitosan hydrogel shell to create a cell-friendly bioactive environment within its pores. The physicochemical, morphological, and mechanical characterization of the hybrid structure and of its component materials was carried out by means of infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and mechanical testing under different loading conditions. These hybrid polymer devices were found to closely mimic both the morphology and the stiffness of bones. In addition, in vitro studies showed that the core-shell scaffolds are efficiently seeded by human mesenchymal stromal cells, which remain viable, proliferate, and are capable of differentiating towards the osteogenic phenotype if adequately stimulated.     

Development of Core-Shell Nanoparticle Drug Delivery Systems Based on Biomimetic Mineralization

Among various drug-delivery systems, core-shell nanoparticles have many advantages. Inspired by nature, biomimetic synthesis has emerged as a new strategy for making core-shell nanoparticles in recent years. Biomimetic mineralization is the process by which living organisms produce minerals based on biomolecule templating that leads to the formation of hierarchically structured organic–inorganic materials. In this minireview, we mainly focus on the synthesis of core-shell nanoparticle drug-delivery systems by biomimetic mineralization. We review various biomimetic mineralization methods for fabricating core-shell nanoparticles including silica-based, calcium-based and other nanoparticles, and their applications in drug delivery. We also summarize strategies for drug loading in the biomolecule-mineralized core-shell NPs. Current challenges and future directions are also discussed.