A photocrosslinkable and hemostatic bilayer wound dressing based on gelatin methacrylate hydrogel and polyvinyl alcohol foam for skin regeneration.

The enormous potential of multifunctional bilayer wound dressings in various medical interventions for wound healing has led to decades of exploration into this field of medicine. However, it is usually difficult to synthesize a single hydrogel with all the required capabilities simultaneously. This paper proposes a bilayer model with an outer layer intended for hydrogel wound treatment. By adding gelatin methacrylate (GelMA) and tannic acid (TA) to the hydrogel composition and using polyvinyl alcohol-carboxymethyl chitosan (PVA-CMCs) foam layer as supports, a photocrosslinkable hydrogel with an optimal formulation was created. The hydrogels were then examined using a range of analytical procedures, including mechanical testing, rheology, chemical characterization, and in vitro and in vivo tests. The resulting bilayer wound dressing has many desirable properties, namely uniform adhesion and quick crosslinking by UV light. When used against Gram-positive and Gram-negative bacterial strains, bilayer wound dressings demonstrated broad antibacterial efficacy. In bilayer wound dressings with GelMA and TA, better wound healing was observed. Those without these elements showed less effectiveness in healing wounds. Additionally, encouraging collagen production and reducing wound infection has a major therapeutic impact on wounds. The results of this study could have a significant impact on the development of better-performing wound dressings.

Tailorable mechanical and degradation properties of KCl-reticulated and BDDE-crosslinked PCL/chitosan/κ-carrageenan electrospun fibers for biomedical applications: Effect of the crosslinking-reticulation synergy.

The development of intricated and interconnected porous mats is desired for many applications in biomedicine and other relevant fields. The mats that comprise the use of natural, bioactive, and biodegradable polymers are the focus of current research activities. In the present work, crosslinked fibers with improved characteristics were produced by incorporating 1,4-butanediol diglycidyl ether (BDDE) into a polymer formulation containing polycaprolactone (PCL), chitosan (CS), and κappa-carrageenan (κ-C). A slight variation of formic acid (FA)/acetic acid (AA) ratio used as a solvent system, significantly affected the characteristics of the produced fiber mats. Both polysaccharides and BDDE played a major role in tailoring mechanical properties when fibrous scaffolds were reticulated under KCl-mediated basic conditions for determined periods of time at 50 °C. In vitro biological assessment of the electrospun fiber mats revealed proliferation of MC3T3-E1 cells when incubated for 1 and 7 days. After staining the cells with 4',6-diamidino-2-phenylindole (DAPI)/rhodamine phalloidin an autofluorescence response was observed by fluorescence microscopy in the scaffold manufactured using a solvent with higher FA/AA ratio due to the formation of microfibers. The results demonstrated the potential of the BDDE-crosslinked PCL/CS/κ-C electrospun fibers as promising materials for biomedical applications that may include soft and bone tissue regeneration.

Environmentally friendly fabrication of electrospun nanofibers made of polycaprolactone, chitosan andκ-carrageenan (PCL/CS/κ-C).

Electrospun fibers based on biodegradable polyanionic or polycationic biopolymers are highly beneficial for biomedical applications. In this work, electrospun nanofibers made from poly(epsilon caprolactone) (PCL), chitosan (CS) andκ-carrageenan (κ-C) were successfully fabricated using several mixtures of benign solvents containing formic acid and acetic acid. The addition ofκ-C improved the preparation procedure for the production of PCL/CS fibers by electrospinning. Moreover, a polymer mixture was selected to be stored at -20 °C for one month with the purpose to study the properties of the resulting fiber mat. The results indicated that fiber characteristics were not seriously compromised compared to the ones of those fabricated with the original solution, which represents an important reduction in produced waste. Thus, the interactions that occur between positively and negatively charged hydrophilic polysaccharides might induce higher stability to the linear aliphatic polyester in the polymer mixture. All fiber mats were morphologically, physico-chemically and mechanically characterized, showing average fiber diameters in the nano scale. A direct cell viability assay using ST-2 cells demonstrated cell proliferation after seven days of incubation for all prepared fiber mats, confirming their suitability as potential candidates for bone tissue engineering and wound healing applications.

Polymer-Derived Biosilicate®-like Glass-Ceramics: Engineering of Formulations and Additive Manufacturing of Three-Dimensional Scaffolds.

Silicone resins, filled with phosphates and other oxide fillers, yield upon firing in air at 1100 °C, a product resembling Biosilicate® glass-ceramics, one of the most promising systems for tissue engineering applications. The process requires no preliminary synthesis of parent glass, and the polymer route enables the application of direct ink writing (DIW) of silicone-based mixtures, for the manufacturing of reticulated scaffolds at room temperature. The thermal treatment is later applied for the conversion into ceramic scaffolds. The present paper further elucidates the flexibility of the approach. Changes in the reference silicone and firing atmosphere (from air to nitrogen) were studied to obtain functional composite biomaterials featuring a carbon phase embedded in a Biosilicate®-like matrix. The microstructure was further modified either through a controlled gas release at a low temperature, or by the revision of the adopted additive manufacturing technology (from DIW to digital light processing).

Combination of Selective Etching and Impregnation toward Hollow Mesoporous Bioactive Glass Nanoparticles.

In this study, binary SiO2-CaO hollow mesoporous bioactive glass nanoparticles (HMBGNs) are prepared by combing selective etching and impregnation strategies. Spherical silica particles (SiO2 NPs) are used as hard cores to assemble cetyltrimethylammonium bromide (CTAB)/silica shells, which are later removed by selective etching to generate a hollow structure. After the removal of CTAB by calcination, the mesoporous shell of particles is formed. Calcium (Ca) is incorporated into the particles using impregnation by soaking the etched SiO2 NPs in calcium nitrate aqueous solution. The amount of incorporated Ca is tailorable by controlling the ratio of SiO2 NPs:calcium nitrate in the soaking solution. The produced HMBGNs are bioactive, as indicated by the rapid formation of hydroxyapatite on their surfaces after immersion in simulated body fluid. In a direct culture with MC3T3-E1 cells, HMBGNs were shown to exhibit concentration-dependent cytotoxicity and can stimulate osteogenic differentiation of MC3T3-E1 cells at concentrations of 1, 0.5, and 0.25 mg/mL. Our results indicate that the combination of selective etching and impregnation is a feasible approach to produce hierarchical HMBGNs. The produced hollow particles have potential in drug delivery and bone tissue regeneration applications, and should be further investigated in detailed in vitro and in vivo studies.

Cerium and gallium containing mesoporous bioactive glass nanoparticles for bone regeneration: Bioactivity, biocompatibility and antibacterial activity.

In recent years, mesoporous bioactive glass nanoparticles (MBGNPs) have generated great attention in biomedical applications. In this study, cerium and gallium doped MBGNPs were prepared by microemulsion assisted sol-gel method in the binary SiO2-CaO system. MBGNPs with spheroidal and pineal shaped morphology were obtained. Nitrogen sorption analysis elucidated the mesoporous structure of synthesized nanoparticles with high specific surface area. X-ray diffraction analysis confirmed the amorphous nature of the nanoparticles. The chemical compositions of all samples were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES), which revealed that the contents of cerium and gallium could be tailored by adjusting the concentrations of the precursors used for the synthesis. All MBGNPs exhibited in vitro bioactivity when immersed in simulated body fluid, except the particles doped with higher amounts than 1 mol% of cerium. MBGNPs showed antibacterial activity against S. aureus and E. coli without exhibiting cytotoxicity towards MG-63 osteoblast-like cells. Mentioned features of the obtained Ce and Ga-doped MBGNPs make them useful for multifunctional applications such as drug delivery carriers or bioactive fillers for bone tissue engineering applications.

Electrospun PCL Fiber Mats Incorporating Multi-Targeted B and Co Co-Doped Bioactive Glass Nanoparticles for Angiogenesis.

Vascularization is necessary in tissue engineering to keep adequate blood supply in order to maintain the survival and growth of new tissue. The synergy of biologically active ions with multi-target activity may lead to superior angiogenesis promotion in comparison to single-target approaches but it has been rarely investigated. In this study, polycaprolactone (PCL) fiber mats embedded with B and Co co-doped bioactive glass nanoparticles (BCo.BGNs) were fabricated as a tissue regeneration scaffold designed for promoting angiogenesis. BCo.NBGs were successfully prepared with well-defined spherical shape using a sol-gel method. The PCL fiber mats embedding co-doped bioactive glass nanoparticles were fabricated by electrospinning using benign solvents. The Young's moduli of the nanoparticle containing PCL fiber mats were similar to those of the neat fiber mats and suitable for scaffolds utilized in soft tissue repair approaches. The mats also showed non-cytotoxicity to ST-2 cells. PCL fiber mats containing BCo.BGNs with a relatively high content of B and Co promoted the secretion of vascular endothelial growth factor to a greater extent than PCL fiber mats with a relatively low B and Co contents, which demonstrates the potential of dual ion release (B and Co) from bioactive glasses to enhance angiogenesis in soft tissue engineering.

Multi-targeted B and Co co-doped 45S5 bioactive glasses with angiogenic potential for bone regeneration.

Many elements, such as copper, cobalt (Co), strontium, magnesium and boron (B) have been used for single or multiple doping of bioactive glasses to promote angiogenesis during bone regeneration. However, few works have focused on promoting angiogenesis through stimulating several different signalling pathways which can be called a multi-target approach. In this study, 45S5 bioactive glass (BG) co-doped with B and Co was prepared by conventional melt quenching method. The synergistic effect of the two co-doping elements on angiogenesis promotion was expected. ATR-Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy and inductively coupled plasma-optical emission spectrometry were used to characterize the composition, element distribution and ion release of the samples, respectively. Results showed that the compositions of all samples were consistent with the design compositions and all elements were homogeneously distributed in the bulk glass. Different contents of B and Co led to different release rates of these elements. All samples showed bioactivity after immersion in simulated body fluid, regardless of the amount of doped B and Co. The 1% and 0.1% extracts of all samples did not show any cytotoxicity to MG-63 and ST-2 cells. Compared with single B or Co doping, the B and Co dual doped sample led to a stronger increase of the secretion of vascular endothelial growth factor from ST-2 cells, which supports and confirms the synergistic effect on angiogenesis of B and Co as co-doping elements in 45S5 BG.

Multifunctional zinc ion doped sol - gel derived mesoporous bioactive glass nanoparticles for biomedical applications.

Mesoporous bioactive glasses have been widely investigated for applications in bone tissue regeneration and, more recently, in soft tissue repair and wound healing. In this study we produced mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO2-CaO system. With the intention of adding subsidiary biological function, MBGNs were doped with Zn2+ ions. Zn-MBGNs with 8 mol% ZnO content were synthesized via microemulsion assisted sol-gel method. The synthesized particles were homogeneous in shape and size. They exhibited spherical shape, good dispersity, and a size of 130 ±â€¯10 nm. The addition of zinc precursors did not affect the morphology of particles, while their specific surface area increased in comparison to MBGNs. The presence of Zn2+ ions inhibited the formation of hydroxycarbonate apatite (HCAp) on the particles after immersion in simulated body fluid (SBF). No formation of HCAp crystals on the surface of Zn-MBGNs could be observed after 14 days of immersion. Interestingly, powders containing relatively high amount of zinc released Zn2+ ions in low concentration (0.6-1.2 mg L-1) but in a sustained manner. This releasing feature enables Zn-MBGNs to avoid potentially toxic levels of Zn2+ ions, indeed Zn-MBGNs were seen to improve the differentiation of osteoblast-like cells (MG-63). Additionally, Zn-MBGNs showed higher ability to adsorb proteins in comparison to MBGNs, which could indicate a favourable later attachment of cells. Due to their advantageous morphological and physiochemical properties, Zn-MBGNs show great potential as bioactive fillers or drug delivery systems in a variety of applications including bone regeneration and wound healing.