Morphology Of Scaffolds Research Articles

A novel 3D co-culture platform for integrating tissue interfaces for tumor growth, migration and therapeutic sensitivity: “PP-3D-S”

Metastatic cancers can be highly heterogeneous, show large patient variability and are typically hard to treat due to chemoresistance. Personalized therapies are therefore needed to suppress tumor growth and enhance patient's quality of life. Identifying appropriate patient-specific therapies remains a challenge though, due mainly to non-physiological in vitro culture systems. Therefore, more complex and physiological in vitro human cancer microenvironment tools could drastically aid in development of new therapies. We developed a plasma-modified, electro-spun 3D scaffold (PP-3D-S) that can mimic the human cancer microenvironment for customized-cancer therapeutic screening. The PP-3D-S was characterized for optimal plasma-modifying treatment and scaffolds morphology including fiber diameter and pore size. PP-3D-S was then seeded with human fibroblasts to mimic a stromal tissue layer; cell adhesion on plasma-modified poly (lactic acid), PLA, electrospun mats vastly exceeded that on untreated controls. The cell-seeded scaffolds were then overlaid with alginate/gelatin-based hydrogel embedded with MDA-MB231 human breast cancer cells, representing a tumor-tissue interface. Among three different plasma treatments, we found that NH3 plasma promoted the most tumor cell migration to the scaffold surfaces after 7 days of culture. For all treated and non-treated mats, we observed a significant difference in tumor cell migration between small-sized and either medium- or large-sized scaffolds. In addition, we found that the PP-3D-S was highly comparable to the standard Matrigel® migration assays in two different sets of doxorubicin screening experiments, where 75% reduction in migration was achieved with 0.5 μM doxorubicin for both systems. Taken together, our data indicate that PP-3D-S is an effective, low-cost, and easy-to-use alternate 3D tumor migration model which may be suitable as a physiological drug screening tool for personalized medicine against metastatic cancers.

Core-Shell Magnetoactive PHB/Gelatin/Magnetite Composite Electrospun Scaffolds for Biomedical Applications.

Novel hybrid magnetoactive composite scaffolds based on poly(3-hydroxybutyrate) (PHB), gelatin, and magnetite (Fe3O4) were fabricated by electrospinning. The morphology, structure, phase composition, and magnetic properties of composite scaffolds were studied. Fabrication procedures of PHB/gelatin and PHB/gelatin/Fe3O4 scaffolds resulted in the formation of both core-shell and ribbon-shaped structure of the fibers. In case of hybrid PHB/gelatin/Fe3O4 scaffolds submicron-sized Fe3O4 particles were observed in the surface layers of the fibers. The X-ray photoelectron spectroscopy results allowed the presence of gelatin on the fiber surface (N/C ratio–0.11) to be revealed. Incubation of the composite scaffolds in saline for 3 h decreased the amount of gelatin on the surface by more than ~75%. The differential scanning calorimetry results obtained for pure PHB scaffolds revealed a characteristic melting peak at 177.5 °C. The presence of gelatin in PHB/gelatin and PHB/gelatin/Fe3O4 scaffolds resulted in the decrease in melting temperature to 168–169 °C in comparison with pure PHB scaffolds due to the core-shell structure of the fibers. Hybrid scaffolds also demonstrated a decrease in crystallinity from 52.3% (PHB) to 16.9% (PHB/gelatin) and 9.2% (PHB/gelatin/Fe3O4). All the prepared scaffolds were non-toxic and saturation magnetization of the composite scaffolds with magnetite was 3.27 ± 0.22 emu/g, which makes them prospective candidates for usage in biomedical applications.

3D‐Printed Polyurethane Tissue‐Engineering Scaffold with Hierarchical Microcellular Foam Structure and Antibacterial Properties

This work proposes a facile fabrication strategy of polyurethane (TPU) tissue‐engineering scaffold with hierarchical structure, designed by combination of the fused deposition modeling (FDM) 3D printing and supercritical microcellular foaming by carbon dioxide (CO2). Further surface modification of TPU scaffold with graphene oxide (GO) was carried out by in situ polymerization of polydopamine (PDA) to ensure stable loading of GO with antibacterial properties. The influence of 3D‐printing temperature and speed on the microcellular cell morphology of TPU scaffold was investigated and optimized. The microcellular foaming and expansion process was indicated to compensate mechanical loss because of the gaps of stacking layers by FDM printing, and the reported tensile strength of 28 MPa matched well with that of natural cartilage tissue constructs. More interesting, the formation of interconnected open pores on the surface of foamed TPU scaffold shows much more enhanced cell adhesion because of the bigger specific surface area of microcellular structure. Similarly, the foamed TPU scaffold exhibits good absorption of GO nanosheets by the synthesized PDA on the surface and antibacterial properties, compared with the unfoamed TPU scaffold. This work offers a strategy for designing and manufacturing polymer tissue‐engineering scaffold with hierarchical structure and good antibacterial property.

Reactive Magnetron Plasma Modification of Electrospun PLLA Scaffolds with Incorporated Chloramphenicol for Controlled Drug Release.

Surface modification with the plasma of the direct current reactive magnetron sputtering has demonstrated its efficacy as a tool for enhancing the biocompatibility of polymeric electrospun scaffolds. Improvement of the surface wettability of materials with water, as well as the formation of active chemical bonds in the near-surface layers, are the main reasons for the described effect. These surface effects are also known to increase the release rate of drugs incorporated in fibers. Herein, we investigated the effect of plasma modification on the chloramphenicol release from electrospun poly (lactic acid) fibrous scaffolds. Scaffolds with high—50 wt./wt.%—drug content were obtained. It was shown that plasma modification leads to an increase in the drug release rate and drug diffusion coefficient, while not deteriorating surface morphology and mechanical properties of scaffolds. The materials’ antibacterial activity was observed to increase in the first day of the experiment, while remaining on the same level as the unmodified group during the next six days. The proposed technique for modifying the surface of scaffolds will be useful for obtaining drug delivery systems with controlled accelerated release, which can expand the possibilities of local applications of antibiotics and other drugs.

Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model.

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.

The effect of surface morphology on endothelial and smooth muscle cells growth on blow-spun fibrous scaffolds

This study aimed to analyze the growth of two types of blood vessel building cells: endothelial cells (ECs) and smooth muscle cells (SMCs) on surfaces with different morphology. Two types of materials, differing in morphology, were produced by the solution blow spinning technique. One-layer materials consisted of one fibrous layer with two fibrous surfaces. Bi-layer materials consisted of one fibrous-solid layer and one fibrous layer, resulting in two different surfaces. Additionally, materials with different average fiber diameters (about 200, 500, and 900 nm) were produced for each group. It has been shown that it is possible to obtain structures with a given morphology by changing the selected process parameters (working distance and polymer solution concentration). Both morphology (solid versus fibrous) and average fiber diameter (submicron fibers versus microfibers) of scaffolds influenced the growth of ECs. However, this effect was only visible after an extended period of culture (6 days). In the case of SMCs, it was proved that the best growth of SMCs is obtained for micron fibers (with an average diameter close to 900 nm) compared to the submicron fibers (with an average diameter below 900 nm).

Development of alginate-chitosan composite scaffold incorporation of bacterial cellulose for bone tissue engineering

On account of the excellent biocompatibility and biodegradability of natural polymers, such as alginate, chitosan (CS), and bacterial cellulose (BC), we developed the alginate/bacterial cellulose-chitosan (Alg/BC-CS) composite scaffolds through the incorporation of BC into alginate matrix and the surface coverage of CS, using hydroxyapatite/D-glucono-δ-lactone (HAP/GDL) complex as the gelling system. The effects of the addition of BC on the scaffold morphology, porosity, mechanical property, swelling, degradability, protein adsorption, and release properties, and cytocompatibility were investigated. The fabricated Alg/BC-CS composite scaffolds revealed the regular 3D morphology due to the homogeneous cross-linking by HAP/GDL complex. The incorporation of the BC significantly reduced their pore size, making Alg/BC-CS composite hydrogel more beneficial to favor tissue ingrowth and ensure mechanical integrity. Moreover, the tight fiber network structure and good barrier properties of BC and its formation of intermolecular hydrogen bonds with alginate could effectively control swelling behaviors and inhibit the degradation of Alg/BC-CS composite scaffolds. Meanwhile, the resultant Alg/BC-CS composite scaffolds showed good apatite formation ability, protein adsorption, and release performance, as well as excellent cytocompatibility, so they could exhibit great application potentials for bone tissue engineering.

A comparison between β-tricalcium phosphate and chitosan poly-caprolactone-based 3D melt extruded composite scaffolds.

Melt extrusion 3D printing has become an attractive additive manufacturing technology to construct degradable scaffolds as tissue precursors in order to create clinically relevant medical devices. Towards this end, a commonly used synthetic polyester, poly-caprolactone (PCL), was used to make scaffolds composed of different biomaterial compositions to increase bioactivity using 3D melt pneumatic extrusion technology. Varying ratios of the natural biopolymer, chitosan, or the bioceramic, β-tricalcium phosphate (TCP) were blended with PCL to fabricate support scaffolds with three-dimensional (3D) architecture for human bone-marrow derived mesenchymal stem cell (hBMSC) growth for potential bone regeneration application. In this study, basic printing requirements as well as biomaterial dynamic mechanical (DMA), elemental, and thermogravimetric (TGA) analysis results demonstrate material homogeneity as well as thermal stability. Scaffold morphology and microarchitecture were assessed using scanning electron microscopy (SEM) alongside in vitro scaffold degradation and biological characterisation. Human BMSC proliferation was assessed using fluorescence imaging, and quantitated via the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. These in vitro cell viability studies revealed that the highest chitosan concentration blend of 20% favoured the most hBMSC growth, exhibited the most swelling, and showed minimal degradation after 28 days. The 20% TCP blend had the second highest hBMSC growth, exhibited moderate swelling, and the fastest degradation rate. Overall, this study demonstrates the first direct comparison of a natural biopolymer-based, that is, chitosan, 3D melt extruded PCL composite with that of a bioceramic-based, that is, β-TCP, PCL composite and their effects on hBMSC 3D proliferation. 3D melt extruded PCL-based composite scaffolds methodology offers a straightforward way to print scaffolds with good shape fidelity, interconnected porosities and enhanced bioactivity; and demonstrates their potential use for regenerative, bone repair applications.

Fabrication of a multi-layered decellularized amniotic membranes as tissue engineering constructs

As a promising approach in tissue engineering, decellularization has become one of the mostly-studied research areas in tissue engineering thanks to its potential to bring about several advantages over synthetic materials since it can provide a 3-dimensional ECM structure with matching biomechanical properties of the target tissue. Amniotic membranes are the tissues that nurture the embryos during labor. Similarly, these materials have also been proposed for tissue regeneration in several applications. The main drawback in using amniotic membranes is the limited thickness of these materials since most tissues require a 3D matrix for an enhance regeneration. In order to prevent this limitation, here we report a facile fabrication methodology for multilayered amniotic membrane-based tissue constructs. The amniotic membranes of Wistar albino rats were first decellularized with the physical and chemical methods and utilized as scaffolds. Secondly, the prepared decellularized membranes were sutured to form a multilayered 3D structure. Within the study, 7 groups including control (PBS), were prepared based on physical and chemical decellularization methods. UV exposure and freezing techniques were used as a physical decellularization methods while hypertonic medium and SDS (sodium dodecyl sulfate) protocols were used as chemical decellularization methods. The combinations of both protocols were also used. In groups, A was the control and group B was applied just UV. In group C was applied UV and freezing. In addition to UV and freezing, in group D was applied hypertonic solution while group E was applied SDS (0.03 %). In group F was applied UV, freezing, hypertonic solution and SDS (0.03 %). In group G was applied UV, hypertonic solution, SDS (0.03 %) and freezing, respectively. Based on the histological and quantitative analyses, F and G groups were found as the most efficient decellularization protocols in rat amniotic membranes. Then, group F and G decellularized amniotic membranes were used to form scaffolds and thus-formed matrices were further characterized in vitro cell culture studies and mechanical tests. Cytotoxicity analyses performed using MTT showed a good cell viability in F and G groups scaffolds. The percentage viability rate was higher in G group (81.3 %) compared to F (75.33 %) and also cell viability in G group was found more meaningful according to p value which was obtained 0.007. Cellular adhesions after in vitro cell culture and morphology of scaffolds were evaluated by scanning electron microscopy (SEM). It was observed that the cells cultivated in equal amounts of tissue scaffolds were higher in the F compared to that observed in group G. The mechanical testing with 40 N force revealed 0.77 mm displacement in group F while it was 0.75 mm in group G. Moreover, according to force-controlled test, 2.9 mm displacement of F group and 1.2 mm displacement of G group was measured. As a result, this study shows that the multilayered decellularized amniotic membrane scaffolds support cell survival and adhesion and can form a flexible biomaterial with desired handling properties.

3D Printing of Alginate-Natural Clay Hydrogel-Based Nanocomposites.

Biocompatibility, biodegradability, shear tinning behavior, quick gelation and an easy crosslinking process makes alginate one of the most studied polysaccharides in the field of regenerative medicine. The main purpose of this study was to obtain tissue-like materials suitable for use in bone regeneration. In this respect, alginate and several types of clay were investigated as components of 3D-printing, nanocomposite inks. Using the extrusion-based nozzle, the nanocomposites inks were printed to obtain 3D multilayered scaffolds. To observe the behavior induced by each type of clay on alginate-based inks, rheology studies were performed on composite inks. The structure of the nanocomposites samples was examined using Fourier Transform Infrared Spectrometry and X-ray Diffraction (XRD), while the morphology of the 3D-printed scaffolds was evaluated using Electron Microscopy (SEM, TEM) and Micro-Computed Tomography (Micro-CT). The swelling and dissolvability of each composite scaffold in phosfate buffer solution were followed as function of time. Biological studies indicated that the cells grew in the presence of the alginate sample containing unmodified clay, and were able to proliferate and generate calcium deposits in MG-63 cells in the absence of specific signaling molecules. This study provides novel information on potential manufacturing methods for obtaining nanocomposite hydrogels suitable for 3D printing processes, as well as valuable information on the clay type selection for enabling accurate 3D-printed constructs. Moreover, this study constitutes the first comprehensive report related to the screening of several natural clays for the additive manufacturing of 3D constructs designed for bone reconstruction therapy.

Three-dimensional bioprinting of bioactive scaffolds with thermally embedded abalone shell particles for bone tissue engineering

Abalone shells, which contain both organic and inorganic matter, can facilitate bone remodeling and have been used to fabricate three-dimensional (3D)-printed scaffolds for bone regeneration. Herein, polycaprolactone (PCL) scaffolds were fabricated using 3D printing with abalone shell particles (ASPs) used in high-temperature processing. ASPs were heated to approximately the melting point of PCL and thermally embedded in 3D-printed PCL using a relatively simple process. The morphology and roughness of the composite scaffold changed according to the weight of ASPs used. The scaffolds were grouped as follows: ASP25 (25 mg), ASP50 (50 mg), and ASP100 (100 mg). The ASP25 group exhibited optimum cell viability and proliferation because of the direct influence of roughness and rapid pH changes. The ASP25 and ASP100 groups showed the highest alkaline phosphatase activity. This could be attributed to the effect of the alkaline environment, dissolution of calcium ions, and presence of bioactive molecules in the ASPs that could support bone regeneration. Therefore, the ASP25 group was the most suitable for fabricating bone scaffolds. This study revealed the potential applicability of ASP-embedded scaffolds in bone tissue engineering involving natural bio-organisms that self-mineralize in a process similar to human bone formation.

Nanostructured ligament and fiber Al–doped Li7La3Zr2O12 scaffolds to mediate cathode-electrolyte interface chemistry

Scaffold structures of electrospun aluminum–substituted lithium lanthanum zirconate Li 7 La 3 Zr 2 O 12 (Al-LLZO) were synthesized and used as an additive in a LiNi 0.6 Mn 0.2 Co 0.2 O 2 composite cathode. The scaffolds were crystalized in the cubic phase after calcination at 700 °C. The Al-LLZO scaffold morphology was dependent on the precursor formulation (aqueous and dimethylformamide. The aqueous precursors resulted in scaffolds of densely coalesced ligaments, whereas the dimethylformamide precursors resulted in high–aspect ratio nanofiber scaffolds. The long-term cycling stability and rate performance of the cells were found to depend on the Al-LLZO scaffold morphology. The uniformly dispersed Al-LLZO fibers resulted in a more stable cathode electrolyte interface formation through the reduced decomposition of the LiPF 6 salt during cycling, resulting in a better high-rate and long-term cycling performance. • Crystallization in the cubic phase after calcination at 700 °C for 1 h • Stable CEI for the composite cathodes filled will Al-LLZO fiber scaffolds. • Better cycling performance for the Al-LLZO fiber composite cathodes.

Fabrication and evaluation of homogeneous alginate/polyacrylamide–chitosan–gelatin composite hydrogel scaffolds based on the interpenetrating networks for tissue engineering

AbstractInterpenetrating polymer network (IPN) is generally considered to be one of the most effective methods for imparting high‐strength mechanical properties to hydrogel materials. To broaden the application of alginate hydrogel in skeletal muscle or muscle tissue engineering, the interpenetrating network technology and layer‐by‐layer (LBL) electrostatic assembly were proposed to fabricate the homogeneous alginate/polyacrylamide–chitosan–gelatin (Alg/PAAM–CS–GT) composite hydrogel scaffolds, using the hydroxyapatite/d‐glucono‐δ‐lactone (HAP/GDL) complex as the gelling system. The effects of different components of alginate/polyacrylamide (Alg/PAAM) on the morphology, mechanical properties, swelling, degradability, and cytocompatibility of the hydrogel scaffolds were comparatively characterized. Experimental results showed that the as‐prepared Alg/PAAM–CS–GT composite hydrogel scaffolds exhibited sharp edges and regular 3D structures. Their pore structure could be regulated by changing the content of PAAM in Alg/PAAM–CS–GT composite hydrogel scaffolds. And the filling of PAAM reduced the pores and thickened the pore walls, which obviously enhanced the mechanical properties of Alg/PAAM–CS–GT composite hydrogel scaffolds. FT‐IR and thermogravimetric analysis showed that O‧‧‧N hydrogen bonding between COOH of SA and NH2 of PAAM could be helpful to improve the thermal stability of the composite hydrogel scaffolds. The swelling and biodegradation measurements indicated that the swelling and degradation of Alg/PAAM–CS–GT composite hydrogel scaffolds could be effectively regulated by changing the component content of the composite hydrogel. In addition, the in vitro cytocompatibility analysis showed that the Alg/PAAM–CS–GT composite hydrogel scaffolds could support the growth of MC3T3‐E1 cells and promote cell proliferation and differentiation. According to the in vitro cytocompatibility test results, the optimum PAAM content for the Alg/PAAM–CS–GT composite hydrogel scaffolds was 60%. Because of good morphology, well‐developed pores, excellent mechanical properties, and high biological activity of Alg/PAAM–CS–GT composite hydrogel scaffolds, they could be suitable for application in the tissue engineering field.

Osteo-conductive hydrogel scaffolds of poly(vinylalcohol) with silk fibroin particles for bone augmentation: Structural formation and in vitro testing

Bone augmentation is an effective approach to treat patients who have bone loss at the maxillofacial area. In this research, osteo-conductive hydrogel scaffolds of poly(vinylalcohol) (PVA) with silk fibroin particles (SFP) were fabricated. The SFP were formed by dropping a solution of silk fibroin into acetone at different volume ratios (v/v) of silk to acetone: 1:3 (SFP-3), 1:6 (SFP-6), 1:12 (SFP-12), and 1:24 (SFP-24). The various SFP solutions were mixed with a PVA solution before fabrication into hydrogels by freeze-thawing. Afterwards, the hydrogels were freeze-dried to fabricate the scaffolds. The particle size and charge, molecular organization, and morphology of the SFP were characterized and observed with dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy (SEM). The morphologies of the hydrogel scaffolds were observed with SEM. Swelling percentage was used to assess the swelling behavior of the hydrogel scaffolds. The mechanical properties were also tested. The scaffolds were cultured with osteoblast cells to test the biological performance, cell viability and performance, alkaline phosphatase activity, calcium deposition, and total protein. The SFP-24 was the smallest in particle size. PVA hydrogel scaffolds with SFP-24 demonstrated low particle aggregation, good particle distribution within the scaffold, and a lower swelling percentage. PVA hydrogel scaffolds with SFP had higher mechanical stability than scaffolds without the SFP. Furthermore, the PVA hydrogel scaffold with SFP-24 had better biological performance. Finally, the results demonstrated that PVA hydrogel scaffolds with SFP-24 showed good osteo-conductive performance which is promising for bone augmentation.

Application of amino acids in the modification of polylactic acid nanofiber scaffolds

In this study, thermal-induced phase separation technology (TIPS) and ammonolysis method were used to prepare modified polylactic acid (PLLA) nanofiber scaffolds with higher hydrophilicity using serine (Ser), glycine (Gly), and lysine (Lys) solutions as ammonolysis agents to prepare modified PLLA nanofibers. The results showed that aminolysis reduced the molecular weight of PLLA, and the introduction of amino acids affected the scaffold morphology and provided a better condition to prepare nanofiber scaffolds. The water contact angle of the modified PLLA nanofiber scaffold prepared by amino acids was improved compared to the unmodified PLLA scaffold. The modified PLLA nanofiber scaffold prepared from Ser, Gly, Lys exhibited lower mechanical properties than the PLLA scaffold prepared from water, meeting the pressure resistance requirements of engineered cartilage tissue scaffolds.

Biofabrication of cell-free dual drug-releasing biomimetic scaffolds for meniscal regeneration

Regenerating the meniscus remains challenging because of its avascular, aneural, and alymphatic nature. Three-dimensional (3D) printing technology provides a promising strategy to fabricate biomimetic meniscal scaffolds with an anisotropic architecture, a proper biomechanical microenvironment, and bioactive components. Herein, 3D printing technology is adopted by coencapsulating chemokines (platelet-derived growth factor-BB, PDGF-BB) and small chondroinductive molecules (kartogenin, KGN) within biomimetic polycaprolactone/hydrogel composite scaffolds. The incorporated PDGF-BB is expected to promote endogenous stem cell homing, and KGN in poly(lactic-co-glycolic) acid microspheres is employed to target the chondrogenesis of resident mesenchymal stem cells (MSCs). First, we chose basic bioinks composed of gelatin methacrylamide and hyaluronic acid methacrylate and then incorporated four concentrations (0%, 0.5%, 1.0%, and 2.0%) of meniscal extracellular matrix into the bioink to systematically study the superiority of these combinations and identify the optimally printable bioink. Next, we investigated the scaffold morphology and drug release profile. The effects of releasing the drugs in a sequentially controlled manner from the composite scaffolds on the fate of MSCs were also evaluated. The biofabricated scaffolds, with and without dual drug loading, were further studied in a rabbit model established with a critical-size medial meniscectomy. We found that meniscal scaffolds containing both drugs had combinational advantages in enhancing cell migration and synergistically promoted MSC chondrogenic differentiation. The dual drug-loaded scaffolds also significantly promoted in vivo neomeniscal regeneration three and six months after implantation in terms of histological and immunological phenotypes. The results presented herein reveal that this 3D-printed dual drug-releasing meniscal scaffold possesses the potential to act as an off-the-shelf product for the clinical treatment of meniscal injury and related joint degenerative diseases.

Biopolymer Hydrogel Scaffolds Containing Doxorubicin as A Localized Drug Delivery System for Inhibiting Lung Cancer Cell Proliferation.

A hydrogel scaffold is a localized drug delivery system that can maintain the therapeutic level of drug concentration at the tumor site. In this study, the biopolymer hydrogel scaffold encapsulating doxorubicin was fabricated from gelatin, sodium carboxymethyl cellulose, and gelatin/sodium carboxymethyl cellulose mixture using a lyophilization technique. The effects of a crosslinker on scaffold morphology and pore size were determined using scanning electron microscopy. The encapsulation efficiency and the release profile of doxorubicin from the hydrogel scaffolds were determined using UV-Vis spectrophotometry. The anti-proliferative effect of the scaffolds against the lung cancer cell line was investigated using an MTT assay. The results showed that scaffolds made from different types of natural polymer had different pore configurations and pore sizes. All scaffolds had high encapsulation efficiency and drug-controlled release profiles. The viability and proliferation of A549 cells, treated with gelatin, gelatin/SCMC, and SCMC scaffolds containing doxorubicin significantly decreased compared with control. These hydrogel scaffolds might provide a promising approach for developing a superior localized drug delivery system to kill lung cancer cells.

Electrospun fibre diameter and its effects on vascular smooth muscle cells

Bypass grafting is a technique used in the treatment of vascular disease, which is currently the leading cause of mortality worldwide. While technology has moved forward over the years, synthetic grafts still show significantly lower rates of patency in small diameter bypass operations compared to the gold standard (autologous vessel grafts). Scaffold morphology plays an important role in vascular smooth muscle cell (VSMC) performance, with studies showing how fibre alignment and surface roughness can modulate phenotypic and genotypic changes. Herein, this study has looked at how the fibre diameter of electrospun polymer scaffolds can affect the performance of seeded VSMCs. Four different scaffolds were electrospun with increasing fibre sizes ranging from 0.75 to 6 µm. Culturing VSMCs on the smallest fibre diameter (0.75 µm) lead to a significant increase in cell viability after 12 days of culture. Furthermore, interesting trends were noted in the expression of two key phenotypic genes associated with mature smooth muscle cell contractility (myocardin and smooth muscle alpha-actin 1), whereby reducing the fibre diameter lead to relative upregulations compared to the larger fibre diameters. These results showed that the smallest (0.75 µm) fibre diameter may be best suited for the culture of VSMCs with the aim of increasing cell proliferation and aiding cell maturity.

Chitosan/PEO nanofibers containing Calendula officinalis extract: Preparation, characterization, in vitro and in vivo evaluation for wound healing applications

Wound healing is a complex pathophysiological process, highlighting the importance of effective and thorough wound care along with the prevention of wound infection, a major barrier that can slow down or even disrupt the healing process. To date, there are plenty of herbal plants well known and historically supernatural, showing profound wound healing effects. Application of such herbal extracts/ingredients in electrospun nanofiber platforms has shown promising outcomes in improving wound healing process. Based on these facts, we loaded Calendula officinalis extract (CO) in chitosan/polyethylene oxide scaffolds (CS/PEO) by electrospinning. Using SEM, morphology of electrospun scaffolds showed a narrow range of fiber diameter, around 143–-252 nm, with uniform and bead-free appearance. FT-IR spectroscopy confirmed the presence of CO extract in nanofibrous scaffolds. Of importance, incorporation of CO extract improved mechanical properties of CS/PEO nanofibers. A 1602 cP reduction in viscosity and a 0.892 ms/cm increase in the conductivity of the solution was observed after addition of the CO extract. CO extract showed strong antibacterial properties with 96% and 94% reduction in Gram positive and Gram negative bacteria, respectively. In vitro studies with fibroblast cells confirmed enhanced proliferation, growth and attachment of the cells. The in vivo and histological analysis of rat wounds, revealed excellent wound healing ability of CS/PEO/CO dressings (87.5 % wound closure after 14 days) via improving collagen synthesis, re-epithelization and remodeling of the tissue. In sum, our findings show that CS/PEO/CO scaffolds can be used as a promising dressing for the treatment of skin wounds.

3D-Printed Polymer-Infiltrated Ceramic Network with Biocompatible Adhesive to Potentiate Dental Implant Applications.

The aim of this work was to prepare and characterize polymer–ceramic composite material for dental applications, which must resist fracture and wear under extreme forces. It must also be compatible with the hostile environment of the oral cavity. The most common restorative and biocompatible copolymer, 2,2-bis(p-(2′-2-hydroxy-3′-methacryloxypropoxy)phenyl)propane and triethyleneglycol dimethacrylate, was combined with 3D-printed yttria-stabilized tetragonal zirconia scaffolds with a 50% infill. The proper scaffold deposition and morphology of samples with 50% zirconia infill were studied by means of X-ray computed microtomography and scanning electron microscopy. Samples that were infiltrated with copolymer were observed under compression stress, and the structure’s failure was recorded using an Infrared Vic 2DTM camera, in comparison with empty scaffolds. The biocompatibility of the composite material was ascertained with an MG-63 cell viability assay. The microtomography proves the homogeneous distribution of pores throughout the whole sample, whereas the presence of the biocompatible copolymer among the ceramic filaments, referred to as a polymer-infiltrated ceramic network (PICN), results in a safety “damper”, preventing crack propagation and securing the desired material flexibility, as observed by an infrared camera in real time. The study represents a challenge for future dental implant applications, demonstrating that it is possible to combine the fast robocasting of ceramic paste and covalent bonding of polymer adhesive for hybrid material stabilization.