Methods to improve antibacterial properties of PEEK: A review.

As a thermoplastic and bioinert polymer, polyether ether ketone (PEEK) serves as spine implants, femoral stems, cranial implants, and joint arthroplasty implants due to its mechanical properties resembling the cortical bone, chemical stability, and radiolucency. Although there are standards and antibiotic treatments for infection control during and after surgery, the infection risk is lowered but can not be eliminated. The antibacterial properties of PEEK implants should be improved to provide better infection control. This review includes the strategies for enhancing the antibacterial properties of PEEK in four categories: immobilization of functional materials and functional groups, forming nanocomposites, changing surface topography, and coating with antibacterial material. The measuring methods of antibacterial properties of the current studies of PEEK are explained in detail under quantitative, qualitative, andin vivomethods. The mechanisms of bacterial inhibition by reactive oxygen species generation, contact killing, trap killing, and limited bacterial adhesion on hydrophobic surfaces are explained with corresponding antibacterial compounds or techniques. The prospective analysis of the current studies is done, and dual systems combining osteogenic and antibacterial agents immobilized on the surface of PEEK are found the promising solution for a better implant design.

Bilayer wound dressing composed of asymmetric polycaprolactone membrane and chitosan-carrageenan hydrogel incorporating storax balsam.

A comprehensive approach is needed to develop multifunctional wound dressing that is simple yet efficient. In this work, Liquidambar orientalis Mill. storax loaded hydroxyethyl chitosan (HECS)-carrageenan (kC) based hydrogel (HECS-kC) and polydopamine coated asymmetric polycaprolactone membrane (PCL-DOP) were used to develop a multifunctional and modular bilayer wound dressing. Asymmetric PCL-DOP membrane was prepared by non-solvent induced phase separation (NIPS) followed by polydopamine coating and demonstrated an excellent barrier against bacteria while allowing permeability for 5.45 ppm dissolved­oxygen and 2130 g/m2 water vapor transmission in 24 h in addition to 805 kPa tensile strength. Storax loaded HECS-kC hydrogel, on the other hand, demonstrated a pH-responsive degradation and swelling to provide necessary conditions to facilitate wound healing. The hydrogels showed stretchability above 140 %, mild adhesive strength on sheep skin and PCL-DOP membrane, while the storax incorporation enhanced antibacterial and antioxidant activity. Furthermore, rat full-thickness skin defect model showed that the developed bilayer wound dressing could significantly facilitate wound healing compared to Tegaderm™ and control groups. This study shows that the bilayered wound dressing has the potential to be used as a simple and effective wound care system.

Biosensing of arsenic by whole-cell bacterial bioreporter immobilized on polycaprolactone (PCL) electrospun fiber.

In recent years, heavy metals derived from several anthropogenic sources have both direct and indirect detrimental effects on the health of the environment and living organisms. Whole-cell bioreporters (WCBs) that can be used to monitor the levels of heavy metals in drinking and natural spring waters are important. In this study, whole-cell arsenic bacterial bioreporters were immobilized using polycaprolactone (PCL) electrospun fibers as the support material. The aim is to determine the properties of this immobilized bioreporter system by evaluating its performance in arsenic detection. Within the scope of the study, different growth media and fiber immobilization times were tested to determine the parameters affecting the fluorescent signals emitted by the immobilized bioreporter system in the presence of two dominant forms of arsenic, namely arsenite (As(III)) and arsenate (As(V)). In addition, the sensitivity, selectivity, response time, and shelf-life of the developed bioreporter system were evaluated. As far as the literature is concerned, this is the first study to investigate the potential of using PCL-electrospun fiber-immobilized fluorescent bacterial bioreporter for arsenic detection. This study will open new avenues in environmental arsenic monitoring.

Local application of gingiva-derived mesenchymal stem cells on experimental periodontitis in rats.

BACKGROUND: Stem cell-based approaches in regenerative periodontal therapy have been used in different experimental models. In this study, the effect of local application of gingival mesenchymal stem cells (GMSC) in fibroin/chitosan oligosaccharide lactate hydrogel (F/COS) on periodontal regeneration was evaluated using experimental periodontitis model in rats. METHODS: Mesenchymal stem cells were isolated from the gingiva of rats and characterized. Viability tests and confocal imaging of GMSC in hydrogels were performed. Healthy control without periodontitis (Health; H; n=10), control with periodontitis but no application (Periodontitis; P; n=10), only hydrogel application (F/COS; n=10), and GMSC+F/COS (n=10) four groups were formed for in vivo studies. Experimental periodontitis was created with silk sutures around the maxillary second molars. GMSC labeled with green fluorescent protein (GFP) (250,000 cells/50 µL) in F/COS were applied to the defect. Animals were sacrificed at 2nd and 8th weeks and maxillae of the animals were evaluated by micro-computed tomography (micro-CT) and histologically. The presence of GFP-labeled GMSC was confirmed at the end of 8 weeks. RESULTS: Micro-CT analysis showed statistically significant new bone formation in the F/COS+GMSC treated group compared with the P group at the end of 8 weeks (p < 0.05). New bone formation was also observed in the F/COS group, but the statistical analysis revealed that this difference was not significant when compared with the P group (p > 0.05). Long junctional epithelium formation was less in the F/COS+GMSC group compared with the P group. Periodontal ligament and connective tissue were well-organized in F/COS+GMSC group. CONCLUSION: The results showed that local GMSC application in hydrogel contributed to the formation of new periodontal ligament and alveolar bone in rats with experimental periodontitis. Since gingiva is easly accessible tissue, it is promising for autologous cell-based treatments in clinical applications.

Bioadhesives with Antimicrobial Properties.

Bioadhesives with antimicrobial properties enable easier and safer treatment of wounds as compared to the traditional methods such as suturing and stapling. Composed of natural or synthetic polymers, these bioadhesives seal wounds and facilitate healing while preventing infections through the activity of locally released antimicrobial drugs, nanocomponents, or inherently antimicrobial polers. Although many different materials and strategies are employed to develop antimicrobial bioadhesives, the design of these biomaterials necessitates a prudent approach as achieving all the required properties including optimal adhesive and cohesive properties, biocompatibility, and antimicrobial activity can be challenging. Designing antimicrobial bioadhesives with tunable physical, chemical, and biological properties will shed light on the path for future advancement of bioadhesives with antimicrobial properties. In this review, the requirements and commonly used strategies for developing bioadhesives with antimicrobial properties are discussed. In particular, different methods for their synthesis and their experimental and clinical applications on a variety of organs are reviewed. Advances in the design of bioadhesives with antimicrobial properties will pave the way for a better management of wounds to increase positive clinical outcomes.

Optimization of whole-cell bacterial bioreporter immobilization on electrospun cellulose acetate (CA) and polycaprolactone (PCL) fibers for arsenic detection.

Arsenic contamination is a critical global problem, and its widespread environmental detection is becoming a prominent issue. Herein, electrospun fibers of cellulose acetate (CA) and polycaprolactone (PCL) were successfully fabricated and used as the support material for immobilization of arsenic-sensing bacterial bioreporter for the first time. To date, no attempt has been made to immobilize fluorescent whole-cell bioreporter cells on electrospun fibers for arsenic detection. CA and PCL electrospun fibers were fabricated via traditional electrospinning technique and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and contact angle meter. Following immobilization of the bacterial bioreporter cells, the immobilized bacteria were also characterized by viability assay using AlamarBlue. The effects of growth phase and cell concentration on the fluorescence response of fiber-immobilized arsenic bioreporters to arsenic were also investigated. After immobilization of arsenic bioreporters on 10 wt% PCL fiber, 91% of bacterial cells remained viable, while this value was 55.4% for cells immobilized on 12.5 wt% CA fiber. Bioreporter cells in the exponential growth phase were shown to be more sensitive to arsenic compared to aged cells. While both the electropsun PCL- and CA-immobilized bioreporters successfully detected 50 and 100 µg/L of arsenite (As (III)) concentrations, the PCL-immobilized bioreporter showed better fluorescence performance which should be investigated in future studies. This study helps to fill some gaps in the literature and demonstrates the potential for using electrospun fiber-immobilized arsenic whole-cell bioreporter for arsenic detection in water.

Boron nitride nanofiber/Zn-doped hydroxyapatite/polycaprolactone scaffolds for bone tissue engineering applications.

In this study, Zn doped hydroxyapatite (Zn HA)/boron nitride nanofiber (BNNF)/poly-ε-caprolactone (PCL) composite aligned fibrous scaffolds are produced with rotary jet spinning (RJS) for bone tissue engineering applications. It is hypothesized that addition of Zn HA and BNNF will contribute to cell viability as well as mechanical and osteogenic properties of the PCL scaffolds. Zn HA was synthesized by mixing Ca and P sources followed by sonication and aging whereas BNNF was obtained by the reaction of melamine with boric acid followed by freeze-drying for annealing of fibers. It is found that incorporation of both Zn HA and BNNF in PCL fibers resulted in higher calcium phosphate (CaP) precipitation on the scaffolds. Also, in vitro cell culture studies showed that presence of both Zn HA and BNNF also had synergistic effect for enhanced proliferation and osteogenic activity of Saos-2 cells. Mechanical properties of PCL-Zn HA-BNNF were found similar to that of non-load bearing bones. Furthermore, the presence of Zn HA and BNNF had synergistic effects to cell attachment, proliferation and spreading without causing cytotoxic effect on cells. The highest ALP activity was obtained in the PCL-Zn HA- BNNF group at days 7 and 14 due to release of zinc, calcium, phosphate and boron. Considering its mechanical and bioactivity properties, PCL-Zn HA-BNNF composite scaffolds hold promise as non-load bearing bone substitutes.

3D porous bioceramic based boron-doped hydroxyapatite/baghdadite composite scaffolds for bone tissue engineering.

Making composite scaffolds is one of the well-known methods to improve the properties of scaffolds used in bone tissue engineering. In this study, novel ceramic-based 3D porous composite scaffolds were successfully prepared using boron-doped hydroxyapatite, as the primary component, and baghdadite, as the secondary component. The effects of making composites on the properties of boron-doped hydroxyapatite-based scaffolds were investigated in terms of physicochemical, mechanical, and biological properties. The incorporation of baghdadite contributed to making more porous scaffolds (over 40%) with larger surface area and micropore volumes. The produced composite scaffolds almost solved the low degradation problem of boron-doped hydroxyapatite through the exhibition of higher biodegradation rates, which matched the degradation rate appropriate for the gradual transfer of loads from implants to newly formed bone tissues. Besides higher bioactivity, enhanced cell proliferation, as well as higher osteogenic differentiation (in scaffolds with baghdadite weight greater than 10%), were observed in composite scaffolds due to both physical and chemical modifications that occurred in composite scaffolds. Although our composite scaffolds were slightly weaker than boron-doped hydroxyapatite, their compressive strengths were higher than almost all composite scaffolds made by baghdadite incorporation in the literature. In fact, boron-doped hydroxyapatite provided a base for baghdadite to show mechanical strength suitable for cancellous bone defect treatments. Eventually, our novel composite scaffolds converged the advantages of both components to satisfy the various requirements needed for bone tissue engineering applications and take us one step forward on the road to fabricating an ideal scaffold.

Injectable methacrylated gelatin/thiolated pectin hydrogels carrying melatonin/tideglusib-loaded core/shell PMMA/silk fibroin electrospun fibers for vital pulp regeneration.

Use of injectable hydrogels attract attention in the regeneration of dental pulp due to their ability to fill non-uniform voids such as pulp cavities. Here, gelatin methacrylate/thiolated pectin hydrogels (GelMA/PecTH) carrying electrospun core/shell fibers of melatonin (Mel)-polymethylmethacrylate (PMMA)/Tideglusib (Td)-silk fibroin (SF) were designed as an injectable hydrogel for vital pulp regeneration, through prolonged release of Td and Mel to induce proliferation and odontoblastic differentiation of dental pulp stem cells (DPSC). H NMR and FTIR confirmed methacrylation of Gel and thiolation of Pec. Addition of PMMA/SF increased degradation and water retention capacities of GelMA/PecTH. Rheological analyses and syringe tests proved the injectability of the hydrogel systems. Release studies indicated that Td and Mel were released from the fibers inside the hydrogels sequentially due to their specific locations. This release pattern from the hydrogels resulted in DPSC proliferation and odontogenic differentiation in vitro. Gene expression studies showed that the upregulation of DMP1, DSPP, and Axin-2 genes was promoted by GelMA/PecTH carrying PMMA/SF loaded with Mel (50 µg/mL) and Td (200 nM), respectively. Our results suggest that this hydrogel system holds promise for use in the regeneration of pulp tissue.

Pullulan hydrogel-immobilized bacterial cellulose membranes with dual-release of vitamin C and E for wound dressing applications.

Vitamin C&E (VtC&VtE)-loaded bilayer wound dressings were prepared using bacterial cellulose (BC) synthesized by Acetobacter species and pullulan (PUL). VtC-containing PUL hydrogels (100 µg/mL) were immobilized onto BC by crosslinking. BC/PUL-VtC was loaded with VtE (100 µM in ethanol) by immersion for 2 h. No delamination between the layers was observed via SEM. Despite the porous inner PUL side, the outer BC side exhibited nanofibrous morphology serving as barriers to prevent microorganism invasion. Equilibrium water content of BC/PUL was above 85 % due to the hydrogel characteristics of PUL side, suitable to absorb exudate in wound bed. PUL layer lost >90 % of its weight in simulated wound fluid and > 99 % in lysozyme solution within 14 days, mediating co-release of VtC&VtE. Thin BC side possessed adequate strength (⁓22 MPa) and strain (>30 %) to endure against tensile stress generated by bending on wound surface without rupture, whereas thick PUL side was flexible (>70 % strain) to fit into wound bed under compressive stress without causing harm. In vitro studies using L929 fibroblasts elucidated PUL side was anti-adhesive and removable. Synergistic effect of VtC&VtE on antioxidant activity, wound closure, and collagen synthesis was observed. Thus, BC/PUL-VtC/VtE hold promise as cheap and eco-friendly temporary wound dressing.

Decellularized adipose tissue matrix-coated and simvastatin-loaded hydroxyapatite microspheres for bone regeneration.

Simvastatin (SIM)-loaded and human decellularized adipose tissue (DAT)-coated porous hydroxyapatite (HAp) microspheres were developed for the first time to investigate their potential on bone regeneration. Microspheres were loaded with SIM and then coated with DAT for modifying SIM release and improving their biological response. HAp microspheres were prepared by water-in-oil emulsion method using camphene (C10 H16 ) as porogen followed by camphene removal by freeze-drying and sintering at 1200°C for 3 h. Sintered HAp microspheres with an average particle size of ~400 µm were porous and spherical in shape. Microspheres were incubated with 1, 2.5, and 5 mg/ml SIM stock solutions for drug loading, and drug loading was determined as 7.5 ± 0.79, 20.41 ± 1.93, and 46.26 ± 0.29 µg SIM/mg microspheres, respectively. SIM loading increased with the increase of the initial SIM loading amount. Faster SIM release was observed in DAT-coated microspheres compared to bare counterparts. Higher SaoS-2 cell attachment and proliferation were observed on DAT-coated microspheres. Significantly higher alkaline phosphatase activity of SaoS-2 cells was observed on DAT-coated microspheres containing 0.01 mg/ml SIM than all other groups (p < 0.01). DAT-coated microspheres loaded with SIM at low doses hold promise for bone tissue engineering applications.

Versatile-in-All-Trades: Multifunctional Boron-Doped Calcium-Deficient Hydroxyapatite Directs Immunomodulation and Regeneration.

Osseointegration of implants depends on several intertwined factors: osteogenesis, angiogenesis, and immunomodulation. Lately, novel reinforcements allowing faster bonding with osseous tissue have been explored intensively. In this study, we hypothesized the use of boron as a major multifunctional ion to confer versatility to calcium-deficient hydroxyapatite (cHA) synthesized by a wet precipitation/microwave reflux method. By synthesis of boron-doped calcium-deficient hydroxyapatite (BcHA), we expected to obtain an osteoimmunomodulatory and regenerative nanoreinforcement. BcHA was found to possess a pure HA phase, a greater surface area (66.41 m2/g, p = 0.028), and cumulative concentrations of Ca (207.87 ± 6.90 mg/mL, p < 0.001) and B (112.70 ± 11.79 mg/mL, p < 0.001) released in comparison to cHA. Osteogenic potential of BcHA was analyzed using human fetal osteoblasts. BcHA resulted in a drastic increase in the ALP activity (1.11 ± 0.11 mmol/gDNA·min, p < 0.001), biomineralization rate, and osteogenic gene expressions compared to cHA. BcHA angiogenic potential was investigated using human umbilical cord vein endothelial cells. Significantly, the highest VEGF-A release (1111.14 ± 87.82 in 4 h, p = 0.009) and angiogenic gene expressions were obtained for BcHA-treated samples. These samples were also observed to induce a more prominent and highly branched tube network. Finally, inflammatory and inflammasome responses toward BcHA were elucidated using human monocyte-derived macrophages differentiated from THP-1s. BcHA exhibited lower CAS-1 release (50.18 ± 5.52 µg/gDNA µg/gDNA) and higher IL-10 release (126.97 ± 15.05 µg/gDNA) than cHA. In addition, BcHA treatment led to increased expression of regenerative genes such as VEGF-A, RANKL, and BMP-2. In vitro results demonstrated that BcHA has tremendous osteogenic, angiogenic, and immunomodulatory potential to be employed as a "versatile-in-all-trades" modality in various bone tissue engineering applications.

Potential of pectin for biomedical applications: a comprehensive review.

Pectin is a polysaccharide extracted from various plants, such as apples, oranges, lemons, and it possesses some beneficial effects on human health, including being hypoglycemic and hypocholesterolemic. Therefore, pectin is used in various pharmaceutical and biomedical applications. Meanwhile, its low mechanical strength and fast degradation rate limit its usage as drug delivery devices and tissue engineering scaffolds. To enhance these properties, it can be modified or combined with other organic molecules or polymers and/or inorganic compounds. These materials can be prepared as nano sized drug carriers in the form of spheres, capsules, hydrogels, self assamled micelles, etc., for treatment purposes (mostly cancer). Different composites or blends of pectin can also be produced as membranes, sponges, hydrogels, or 3D printed matrices for tissue regeneration applications. This review is concentrated on the properties of pectin based materials and focus especially on the utilization of these materials as drug carriers and tissue engineering scaffolds, including 3D printed and 3D bioprinted systems covering the studies in the last decade and especially in the last 5 years.

pH responsive release of curcumin from photocrosslinked pectin/gelatin hydrogel wound dressings.

The aim of this study was to develop hydrogel wound dressings made of photocrosslinkable pectin and gelatin with pH dependent release of curcumin, an antimicrobial agent. Methacrylated forms of pectin and gelatin (PeMA and GelMA, respectively) were synthesized, and hydrogels were prepared with different compositions (1:1, 1:2 and 1:3 v/v ratios of PeMA and GelMA) by UV exposure. Pure GelMA was used as control group. Average pore diameter of hydrogels with the highest PeMA content (P1:G1) was 43 µm. All hydrogels showed about 90% swelling. P1:G3 demonstrated the highest stability (retained about 37% of their initial weight after 21 days incubation in PBS), a reasonable compressive modulus (ca. 22 kPa), oxygen permeability (7.44 mg/mL) and preventing ability for bacterial penetration. Therefore, P1:G3 hydrogels were chosen and loaded with curcumin for further studies. In aqueous medium (10 mM PBS, pH 7.4), about 4 times faster release of curcumin was observed than that in medium with pH 5.0. Since infected wounds have alkaline pH compared to healthy tissue, faster release at basic medium is preferable for wound grafts. Disk diffusion tests proved antibacterial efficacy of the hydrogels against S. aureus and E. coli. Live/Dead and Alamar blue assays conducted with L929 fibroblasts showed cytocompatibility of the hydrogels. It was concluded that curcumin loaded P1:G3 hydrogels are promising candidates as wound dressing materials to be further tested in the treatment of infected and chronic wounds.

Natural origin bilayer pullulan-PHBV scaffold for wound healing applications.

Skin tissue loss that occurs by injury and diseases can turn into chronic wounds as a result of complications alongside infection. Chronic wounds fail to heal by themselves and need advanced treatments like engineered wound dressings and regenerative scaffolds. In this study, a novel, natural origin, bilayer electrospun scaffold was produced from pullulan (PUL) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) biopolymers. PHBV production by Cupriavidus necator bacterial strain was optimized and produced polymer was characterized. Characteristic peaks and bands of PHBV were observed by H-NMR and FTIR analyses. Valerate mol percent of produced PHBV copolymer was determined by H-NMR. Average molecular weight of the polymer was determined by SLS technique and crystallinity of PHBV was calculated from DSC curve. Bilayer scaffold was produced by electrospinning of hydrophilic PUL fibrous membrane onto wet-electrospun hydrophobic PHBV 3D fibrous mat. Bilayer scaffold was designed to involve regenerative and barrier fibrous layers. Nano fibrous PUL membrane with smaller pore size was efficient as a barrier against bacterial transmission while enabling optimum oxygen and water vapor transmission. Water retention and degradation properties were found to be optimum for a skin tissue scaffold. In vitro studies showed that PUL membrane sustained L929 cell proliferation while preventing cells from migrating inside the barrier phase while PHBV layer supported cell viability, proliferation, and migration, creating a regenerative 3D structure. Results showed that, novel natural origin PUL/PHBV bilayer scaffold is a promising candidate for wound healing applications.

Lithocholic acid conjugated mPEG-b-PCL micelles for pH responsive delivery to breast cancer cells.

In this study, micelles composed of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) copolymer (mPEG-b-PCL), which has ionically conjugated lithocholic acid (LCA) and providing pH sensitive release of LCA in acidic media, were prepared as drug carrier devices for cancer therapy. Micelles were produced by co-solvent evaporation method at two different temperatures (60 °C and 25 °C) and coded as LCA60**M and LCA25**M, respectively). Hydrodynamic diameters were 86.9 nm and 228.2 nm, and zeta potentials were -7.54 mV and -18.83 mV for LCA60**M and LCA25**M, respectively. For all micelles, release of LCA was higher in acidic media (pH 5.0) compared to physiological media (pH 7.4). Micelles loaded with a fluorescent dye, coumarin 6, demonstrated effective internalization into triple negative MDA-MB-231 breast cancer cells in 4 h. LCA60**M (41.7 ± 1.5%) and LCA25**M (44.5 ± 2.2%) had higher inhibitory effect on the cell migration compared to free LCA (64.7 ± 1.3%). Both LCA conjugated micelles decreased lipogenic activity and increased expressions of Bax (1.3 fold) and p53 (1.2 fold) apoptotic genes. Annexin V-FITC results exhibited high apoptotic cell number after the treatment of MDA-MB-231 cells with micelles. Free LCA and LCA conjugated LCA60**M and LCA25**M micelles decreased mitochondrial transmembrane potential of the cells by 41.8 ± 3.0%, 30.4 ± 0.9%, and 57.1 ± 0.5, respectively. Micelles also caused an effective decrease in angiogenesis ability of HUVECs. The novelty of this study is the prepared micelles, which have ionic conjugation of LCA to mPEG-b-PCL, and pH responsive release of LCA demonstrating effective apoptosis on breast cancer cells. These micelles may have great potential for cancer treatment. However, further in vivo studies are needed before clinical translation.

Properties and applications of boron nitride nanotubes.

Nanomaterials have received increasing attention due to their controllable physical and chemical properties and their improved performance over their bulk structures during the last years. Carbon nanostructures are one of the most widely searched materials for use in different applications ranging from electronic to biomedical because of their exceptional physical and chemical properties. However, BN nanostructures surpassed the attention of the carbon-based nanostructure because of their enhanced thermal and chemical stabilities in addition to structural similarity with the carbon nanomaterials. Among these nanostructures, one dimensional-BN nanostructures are on the verge of development as new materials to fulfill some necessities for different application areas based on their excellent and unique properties including their tunable surface and bandgap, electronic, optical, mechanical, thermal, and chemical stability. Synthesis of high-quality boron nitride nanotubes (BNNTs) in large quantities with novel techniques provided greater access, and increased their potential use in nanocomposites, biomedical fields, and nanodevices as well as hydrogen uptake applications. In this review, properties and applications of one-dimensional BN (1D) nanotubes, nanofibers, and nanorods in hydrogen uptake, biomedical field, and nanodevices are discussed in depth. Additionally, research on native and modified forms of BNNTs and also their composites with different materials to further improve electronic, optical, structural, mechanical, chemical, and biological properties are also reviewed. BNNTs find many applications in different areas, however, they still need to be further studied for improving the synthesis methods and finding new possible future applications.

Coaxial electrospinning of composite mats comprised of core/shell poly(methyl methacrylate)/silk fibroin fibers for tissue engineering applications.

Mimicking extracellular matrix (ECM) of native tissue by tissue-engineered constructs is critical to induce regeneration of the damaged site. In this study, coaxial electrospinning of core/shell poly(methyl methacrylate) (PMMA)/silk fibroin (SF) fibers was optimized for the first time to provide ECM-like microenvironment for new tissue formation by utilization of a new collector design for obtaining homogeneously deposited mats from the collector screen. SF-shell was produced to increase cell-affinity of fiber surfaces whereas PMMA-core was designed to support the tissue mechanically during regeneration. PMMA/SF membranes were characterized. Morphology of core/shell PMMA/SF fibers resembled neat SF (ribbon-like) fibers rather than neat PMMA (cylindrical) fibers since SF constituted the shell part. The average diameter of PMMA/SF fibers (2.51 µm) lied in between the neat counterparts (PMMA: 2.40 µm and SF: 2.84 µm). The morphological and chemical properties affected the water contact angle and porosity of the mats, leading to the highest hydrophilicity for SF mats and the highest porosity for PMMA mats among the groups. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) confirmed the core/shell structure of PMMA/SF fibers. The combination of these remarkably different polymers (synthetic, hydrophobic, brittle PMMA and natural, hydrophilic, flexible SF) resulted in intermediate mechanical properties of PMMA/SF mats both in dry and wet conditions by preserving fibrous and porous structures in the core/shell form unlike the neat mats. Thermogravimetric analyses (TGA) showed the highest mass loss for PMMA/SF mats which lost 13.9% of their initial weight unlike the neat counterparts. In vitro hydrolytic & enzymatic degradation studies revealed that PMMA/SF had the weight loss between those observed for SF and PMMA mats in the presence and absence of enzymes while possessing the highest water uptake capacity. SEM examinations of mats after 14 days of hydrolytic degradation demonstrated the SF-shell of the fibers were fused at the intercept points of the PMMA/SF network while the PMMA-core acted as a separating backbone and preserved fibrous, and hence porous architecture of the mats. Cell culture studies demonstrated that human dental pulp stem cells (DPSC) were able to attach and proliferated on PMMA/SF mats while a lower degree of cell spreading on PMMA mats was observed. DPSC adhesion was improved by SF-shell in PMMA/SF group. In conclusion, electrospun composite mats composed of core/shell PMMA/SF fibers could be considered a promising candidate for tissue engineering applications and drug delivery strategies.

Xanthan-gelatin and xanthan-gelatin-keratin wound dressings for local delivery of Vitamin C.

Recently, functional dressings that can protect the wound area from dehydration and bacterial infection and support healing have gained importance in place of passive dressings. This study aimed to develop temporary and regenerative xanthan/gelatin (XGH) and keratin/xanthan/gelatin hydrogels (KXGHs) that have high absorption capacity and applicability as a wound dressing that can provide local delivery of Vitamin C (VC). Firstly, xanthan/gelatin hydrogels were produced by crosslinking with different glycerol concentrations and characterized to determine the hydrogel composition. According to their weight ratios, xanthan, gelatin, and glycerol hydrogels are named. If their weight ratio is 1:1:2 (w/w/w), the group name is selected as X1:GEL1:GLY2. X1:GEL1:GLY2 hydrogel was selected for biocompatibility, mechanical property, water vapor transmission rate (WVTR), and porosity. The addition of keratin to X1:GEL1:GLY2 improved L929 fibroblasts viability and increased protein release. Water vapor transmission of XGHs and KXGHs was between 3059.09 ± 126 and 4523 ± 133 g m-2 d-1; therefore, they can be suitable for granulating, low to moderate exudate wounds. XGH and KXGHs loaded with VC had higher water uptake, making it more convenient for exudate wounds. VC was released for 100 h, and VC containing XGHs and KXGHs increased the collagen synthesis of L929 fibroblasts. All of the hydrogels (XGH, KXGH, and VC-KXGHs) inhibited the bacteria transmission. In conclusion, our results suggest that VC-XGH and VC-KXGH can be candidates for temporary wound dressing materials for skin wounds.