Showing papers in "Journal of Materials Science: Materials in Medicine in 2020"
TL;DR: Most common biopolymers used in cosmetics are presented in detail together with issues related to skin treatment and hair conditioning and new trends in the preparation of hydrogels based on biopolymer blends as well as bigels have been shown.
Abstract: Hydrogels are cross-linked networks of macromolecular compounds characterized by high water absorption capacity. Such materials find a wide range of biomedical applications. Several polymeric hydrogels can also be used in cosmetics. Herein, the structure, properties and selected applications of hydrogels in cosmetics are discussed in general. Detailed examples from scientific literature are also shown. In this review paper, most common biopolymers used in cosmetics are presented in detail together with issues related to skin treatment and hair conditioning. Hydrogels based on collagen, chitosan, hyaluronic acid, and other polysaccharides have been characterized. New trends in the preparation of hydrogels based on biopolymer blends as well as bigels have been shown. Moreover, biopolymer hydrogels employment in encapsulation has been mentioned.
120 citations
TL;DR: Despite the interesting advances which include the development of hybrid scaffolds, there are still important challenges that need to be addressed in order to fasten translation of scaffolds into the clinical scenario.
Abstract: Bone tissue has an astonishing self-healing capacity yet only for non-critical size defects (<6 mm) and clinical intervention is needed for critical-size defects and beyond that along with non-union bone fractures and bone defects larger than critical size represent a major healthcare problem. Autografts are, still, being used as preferred to treat large bone defects. Mostly, due to the presence of living differentiated and progenitor cells, its osteogenic, osteoinductive and osteoconductive properties that allow osteogenesis, vascularization, and provide structural support. Bone tissue engineering strategies have been proposed to overcome the limited supply of grafts. Complete and successful bone regeneration can be influenced by several factors namely: the age of the patient, health, gender and is expected that the ideal scaffold for bone regeneration combines factors such as bioactivity and osteoinductivity. The commercially available products have as their main function the replacement of bone. Moreover, scaffolds still present limitations including poor osteointegration and limited vascularization. The introduction of pores in scaffolds are being used to promote the osteointegration as it allows cell and vessel infiltration. Moreover, combinations with growth factors or coatings have been explored as they can improve the osteoconductive and osteoinductive properties of the scaffold. This review focuses on the bone defects treatments and on the research of scaffolds for bone regeneration. Moreover, it summarizes the latest progress in the development of coatings used in bone tissue engineering. Despite the interesting advances which include the development of hybrid scaffolds, there are still important challenges that need to be addressed in order to fasten translation of scaffolds into the clinical scenario. Finally, we must reflect on the main challenges for bone tissue regeneration. There is a need to achieve a proper mechanical properties to bear the load of movements; have a scaffolds with a structure that fit the bone anatomy.
70 citations
TL;DR: Fully porous stems without dense shells are concluded to fail under fatigue load, and it is thus safe to use the porous stems with a shell thickness of 1.5 and 2 mm for all porosities.
Abstract: The current study is proposing a design envelope for porous Ti-6Al-4V alloy femoral stems to survive under fatigue loads. Numerical computational analysis of these stems with a body-centered-cube (BCC) structure is conducted in ABAQUS. Femoral stems without shell and with various outer dense shell thicknesses (0.5, 1.0, 1.5, and 2 mm) and inner cores (porosities of 90, 77, 63, 47, 30, and 18%) are analyzed. A design space (envelope) is derived by using stem stiffnesses close to that of the femur bone, maximum fatigue stresses of 0.3σys in the porous part, and endurance limits of the dense part of the stems. The Soderberg approach is successfully employed to compute the factor of safety Nf > 1.1. Fully porous stems without dense shells are concluded to fail under fatigue load. It is thus safe to use the porous stems with a shell thickness of 1.5 and 2 mm for all porosities (18–90%), 1 mm shell with 18 and 30% porosities, and 0.5 mm shell with 18% porosity. The reduction in stress shielding was achieved by 28%. Porous stems incorporated BCC structures with dense shells and beads were successfully printed.
45 citations
TL;DR: Combining the advantage of microtissues to self-assemble and the controlled organization by bioprinting technologies, these ASC spheroids can be useful as building blocks for the engineering of soft tissue implants.
Abstract: The increasing number of mastectomies results in a greater demand for breast reconstruction characterized by simplicity and a low complication profile. Reconstructive surgeons are investigating tissue engineering (TE) strategies to overcome the current surgical drawbacks. 3D bioprinting is the rising technique for the fabrication of large tissue constructs which provides a potential solution for unmet clinical needs in breast reconstruction building on decades of experience in autologous fat grafting, adipose-derived mesenchymal stem cell (ASC) biology and TE. A scaffold was bioprinted using encapsulated ASC spheroids in methacrylated gelatin ink (GelMA). Uniform ASC spheroids with an ideal geometry and diameter for bioprinting were formed, using a high-throughput non-adhesive agarose microwell system. ASC spheroids in adipogenic differentiation medium (ADM) were evaluated through live/dead staining, histology (HE, Oil Red O), TEM and RT-qPCR. Viable spheroids were obtained for up to 14 days post-printing and showed multilocular microvacuoles and successful differentiation toward mature adipocytes shown by gene expression analysis. Moreover, spheroids were able to assemble at random in GelMA, creating a macrotissue. Combining the advantage of microtissues to self-assemble and the controlled organization by bioprinting technologies, these ASC spheroids can be useful as building blocks for the engineering of soft tissue implants.
38 citations
TL;DR: The fabrication of novel gelatin (G)–hydroxyapatite (HA)-/vitamin D (VD)-loaded graphene oxide (GO) scaffolds with different concentrations through solvent-casting method demonstrated the potential of these scaffolds to induce bone regeneration.
Abstract: Developing smart scaffolds with drug release capability is one of the main approaches to bone tissue engineering. The current study involves the fabrication of novel gelatin (G)–hydroxyapatite (HA)-/vitamin D (VD)-loaded graphene oxide (GO) scaffolds with different concentrations through solvent-casting method. Characterizations confirmed the successful synthesis of HA and GO, and VD was loaded in GO with 36.87 ± 4.87% encapsulation efficiency. Physicochemical characterizations showed that the scaffold containing 1% VD-loaded GO had the best mechanical properties and its porosity percentage and density was in the range of natural spongy bone. All scaffolds were degraded after 1-month, subjecting to phosphate buffer saline. The release profile of VD did not match any mathematical kinetics model, porosities and the degradation rate of the scaffolds were dominant controlling factors of release behavior. Studies on the bioactivity of scaffolds immersed in simulated body fluid indicated that VD and HA could encourage the formation of secondary apatite crystals in vitro. Buccal fat pad-derived stem cells (BFPSCs) were seeded on the scaffolds, MTT assay, alkaline phosphatase activity as an indicator of osteoconductivity, and cell adhesion were conducted in order to evaluate in vitro biological responses. All scaffolds highly supported cell adhesion, MTT assay indicated better cell viability in 0.5% VD-loaded GO containing scaffold, and the scaffold enriched with 2% VD-loaded GO performed the most ALP activity. The results demonstrated the potential of these scaffolds to induce bone regeneration.
31 citations
TL;DR: The anti-adhesive and antibacterial properties showed by PEEK at 24 and 48 h against a pioneer such as S. oralis, could have an important role in the prevention of all pathologies connected with biofilm formation, like peri-implantitis in dentistry or prosthetic failures in orthopedics.
Abstract: The aim of this study was to evaluate the interaction between Streptococcus oralis and Polyetheretherketone (PEEK), a novel material recently introduced in implantology. The topographical characterization and the Streptococcus oralis adhesion on this material were compared with other titanium surfaces, currently used for the production of dental implants: machined and double etched (DAE). The superficial micro-roughness of the PEEK discs was analyzed by scanning electron microscopy (SEM) and, the Energy Dispersive Spectrometer (EDS) analyzed their chemical composition. Atomic Force Microscopy (AFM) was used to characterize the micro-topography and the sessile method to evaluate the wettability of the samples. Microbiological analysis measured the colony forming units (CFUs), the biomass (OD570 detection) and the cell viability after 24 and 48 h after Streptococcus oralis cultivation on the different discs, that were previously incubated with saliva. Results showed that PEEK was characterized by a micro-roughness that was similar to machined titanium but at nano-level the nano-roughness was significantly higher in respect to the other samples. The EDS showed that PEEK superficial composition was characterized mainly by Carbonium and Oxygen. The hydrophilicity and wetting properties of PEEK were similar to machined titanium; on the contrary, double etched discs (DAE) samples were characterized by significantly higher levels (p < 0.05). PEEK was characterized by significant lower CFUs, biomass and viable cells in respect to the titanium surfaces. No differences were found between machined and DAE. The anti-adhesive and antibacterial properties showed by PEEK at 24 and 48 h against a pioneer such as S. oralis, could have an important role in the prevention of all pathologies connected with biofilm formation, like peri-implantitis in dentistry or prosthetic failures in orthopedics.
31 citations
TL;DR: It was found that Ba 2+ crosslinked network had more than twice higher storage modulus, and mass decrease to 70% during incubation compared to 42% in case of hydrogels crosslinked with Ca 2+ .
Abstract: Alginate dialdehyde-gelatin (ADA-GEL) hydrogels have been reported to be suitable matrices for cell encapsulation. In general, application of ADA-GEL as bioink has been limited to planar structures due to its low viscosity. In this work, ring shaped constructs of ADA-GEL hydrogel were fabricated by casting the hydrogel into sacrificial molds which were 3D printed from 9% methylcellulose and 5% gelatin. Dissolution of the supporting structure was observed during the 1st week of sample incubation. In addition, the effect of different crosslinkers (Ba2+ and Ca2+) on the physicochemical properties of ADA-GEL and on the behavior of encapsulated MG-63 cells was investigated. It was found that Ba2+ crosslinked network had more than twice higher storage modulus, and mass decrease to 70% during incubation compared to 42% in case of hydrogels crosslinked with Ca2+. In addition, faster increase in cell viability during incubation and earlier cell network formation were observed after Ba2+ crosslinking. No negative effects on cell activity due to the use of sacrificial materials were observed. The approach presented here could be further developed for cell-laden ADA-GEL bioink printing into complex 3D structures.
30 citations
TL;DR: In vitro scratch assay results indicated that H. perforatum oil had a wound healing effect by inducing fibroblast migration and the proliferation study supported these results by increasing fibro Blast proliferation on H.perforatum Oil loaded bilayer membranes.
Abstract: Recently, layered structures composed of nanofibers have gained attention as a novel material to mimic skin tissue in wound healing applications. The aim of this study is to develop a novel hybrid bilayer material composed of zein based composite film and nanofiber layers as a wound dressing material. The upper layer was composed of H. perforatum oil incorporated zein film including MMT and the bottom layer was comprised of 3D electrospun zein/MMT nanofibers to induce wound healing with the controlled release of H. perforatum oil. The bilayer composites were characterized in terms of mechanical test, WVP, water uptake and surface wettability. Antimicrobial activity of the wound dressings against microorganisms were investigated by disc diffusion method. In vitro cytotoxicity of monolayer film and bilayer structure was performed using WST-1 assay on HS2 keratinocyte and 3T3 cell lines. Results indicated that the prepared monolayer films showed appropriate mechanical and gas barrier properties and surface wettability for wound healing. Controlled release of H. perforatum oil was obtained from fabricated membranes up to 48 h. Bilayer membranes showed antimicrobial activity against E. coli, S. aureus, and C. albicans and did not show any toxic effect on NIH3T3 mouse fibroblast and HS2 keratinocyte cell lines. In vitro scratch assay results indicated that H. perforatum oil had a wound healing effect by inducing fibroblast migration. The proliferation study supported these results by increasing fibroblast proliferation on H. perforatum oil loaded bilayer membranes.
29 citations
TL;DR: This review article aims to highlight the biomedical potentials of AAO for applications in tissue replacements along with the mechanism of porous structure formation and pore characteristics in terms of fabrication parameters.
Abstract: Recently, nanomaterials have been widely utilized in tissue engineering applications due to their unique properties such as the high surface to volume ratio and diversity of morphology and structure. However, most methods used for the fabrication of nanomaterials are rather complicated and costly. Among different nanomaterials, anodic aluminum oxide (AAO) is a great example of nanoporous structures that can easily be engineered by changing the electrolyte type, anodizing potential, current density, temperature, acid concentration and anodizing time. Nanoporous anodic alumina has often been used for mammalian cell culture, biofunctionalization, drug delivery, and biosensing by coating its surface with biocompatible materials. Despite its wide application in tissue engineering, thorough in vivo and in vitro studies of AAO are still required to enhance its biocompatibility and thereby pave the way for its application in tissue replacements. Recognizing this gap, this review article aims to highlight the biomedical potentials of AAO for applications in tissue replacements along with the mechanism of porous structure formation and pore characteristics in terms of fabrication parameters.
28 citations
TL;DR: Interestingly, BG-doped Nb scaffolds displayed antibacterial properties, reducing S. lutea and E. coli growth of ≈60% and ≈50%, respectively.
Abstract: Bioactive glasses (BGs), due to their ability to influence osteogenic cell functions, have become attractive materials to improve loaded and unloaded bone regeneration. BG systems can be easily doped with several metallic ions (e.g., Ag, Sr, Cu, Nb) in order to confer antibacterial properties. In particular, Nb, when compared with other metal ions, has been reported to be less cytotoxic and possess the ability to enhance mineralization process in human osteoblast populations. In this study, we co-deposited, through one-pot electrophoretic deposition (EPD), chitosan (CS), gelatin (GE) and a modified BG containing Nb to obtain substrates with antibacterial activity for unloaded bone regeneration. Self-standing composite scaffolds, with a defined porosity (15–90 μm) and homogeneous dispersion of BGs were obtained. TGA analysis revealed a BG loading of about 10% in the obtained scaffolds. The apatite formation ability of the scaffolds was evaluated in vitro in simulated body fluid (SBF). SEM observations, XRD and FT-IR spectra showed a slow (21–28 days) yet effective nucleation of CaP species on BGs. In particular, FT-IR peak around 603 cm−1 and XRD peak at 2θ = 32°, denoted the formation of a mineral phase after SBF immersion. In vitro biological investigation revealed that the release of Nb from composite scaffolds had no cytotoxic effects. Interestingly, BG-doped Nb scaffolds displayed antibacterial properties, reducing S. lutea and E. coli growth of ≈60% and ≈50%, respectively. Altogether, the obtained results disclose the produced composite scaffolds as promising materials with inherent antibacterial activity for bone tissue engineering applications.
26 citations
TL;DR: The strategy of incorporating bioactive glass nanoparticles (BG) in Alg–Gel composite hydrogel represents an easy-to-use approach to the mechanical reinforcement of cell-laden bioink, thus demonstrating their suitability for future applications in extrusion-based bioprinting.
Abstract: Alginate–gelatin (Alg–Gel) composite hydrogel is extensively used in extrusion-based bioprinting. Although Alg–Gel blends possess excellent biocompatibility and printability, poor mechanical properties have hindered its further clinical applications. In this study, a series of design by incorporating bioactive glass nanoparticles (BG) (particle size of 12 and 25 nm) into Alg–Gel hydrogel have been considered for optimizing the mechanical and biological properties. The composite Alg–Gel–BG bioink was biophysically characterized by mechanical tests and bioprinting practice. Biocompatibility of Alg–Gel–BG bioink was then investigated by bioprinting mouse dermal fibroblasts. Mechanical tests showed enhanced stiffness with increasing concentration of incorporated BG. But the maximum concentration of BG was determined 1.0 wt% before blends became too viscous to print. Meanwhile, the incorporation of BG did not affect the highly porous structure and biodegradation of Alg–Gel hydrogel, while the mechanical strength and printability were enhanced. In addition, the cellular proliferation and adhesion in the bioprinted constructs were significantly enhanced by BG (12 nm), while extension was not affected. Therefore, our strategy of incorporating BG in Alg–Gel composite hydrogel represents an easy-to-use approach to the mechanical reinforcement of cell-laden bioink, thus demonstrating their suitability for future applications in extrusion-based bioprinting.
TL;DR: Multi-drug encapsulated bioresorbable and biodegradable electro-sprayed core shell NPs will be promising as a bone substitute for the treatment of osteosarcoma.
Abstract: In bone cancer treatment, local delivery of chemotherapeutic agents is preferred compared to other routes of administration. Delivery of multiple drugs using biodegradable carriers improves the treatment efficiency and overcomes drug resistance and toxicity. With this approach, we have developed multilayer biodegradable core shell nanoparticles (NPs) using the electro-spraying technique to deliver methotrexate (MTX) and doxorubicin (DOX) for the treatment of osteosarcoma. These core-shell NPs with a mean particle size of 212 ± 41 nm consist of hydroxyapatite (HA) and DOX as core with the outer shell made of chitosan (CH) followed by polycaprolactone (PCL) with MTX. The encapsulation efficiency of MTX was around 85% and DOX was 38%. In vitro drug release studies were performed in phosphate buffered saline (PBS) at pH 5 and pH 7.4 for 8 days. Different release profiles were observed in both acidic and alkaline pH. The sequential release of MTX followed by DOX was observed in both pH in sustained manner. Human osteosarcoma MG 63 (OMG-63) cells lines were used to test the cytotoxicity of drug loaded NPs. Multi-drug encapsulated bioresorbable and biodegradable electro-sprayed core shell NPs will be promising as a bone substitute for the treatment of osteosarcoma.
TL;DR: The cultivation of HeLa cells demonstrated their high cytocompatibility and a good activity of gene transfection with enhanced green fluorescent protein (EGFP) as model protein is expected to enhance bone growth around an implanted scaffold or inside a scaffold for tissue engineering.
Abstract: Porous scaffolds of poly(lactide-co-glycolide) (PLGA; 85:15) and nano-hydroxyapatite (nHAP) were prepared by an emulsion-precipitation procedure from uniform PLGA–nHAP spheres (150–250 µm diameter). These spheres were then thermally sintered at 83 °C to porous scaffolds that can serve for bone tissue engineering or for bone substitution. The base materials PLGA and nHAP and the PLGA–nHAP scaffolds were extensively characterized by X-ray powder diffraction, infrared spectroscopy, thermogravimetry, differential scanning calorimetry, and scanning electron microscopy. The scaffold porosity was about 50 vol% as determined by relating mass and volume of the scaffolds, together with the computed density of the solid phase (PLGA–nHAP). The cultivation of HeLa cells demonstrated their high cytocompatibility. In combination with DNA-loaded calcium phosphate nanoparticles, they showed a good activity of gene transfection with enhanced green fluorescent protein (EGFP) as model protein. This is expected enhance bone growth around an implanted scaffold or inside a scaffold for tissue engineering.
TL;DR: The appropriate mechanical strength and high transparency of the cell loaded constructs indicates a viable alternative to the current devices used in the treatment of corneal blindness.
Abstract: Stroma is the main refractive element of the cornea and damage to it is one of the main causes of blindness. In this study, cell loaded hydrogels of methacrylated gelatin (GelMA) and poly(2-hydroxyethyl methacrylate) (pHEMA) (8:2) interpenetrating network (IPN) hydrogels were prepared as the corneal stroma substitute and tested in situ and in vitro. Compressive modulus of the GelMA hydrogels was significantly enhanced with the addition of pHEMA in the structure (6.53 vs 155.49 kPa, respectively). More than 90% of the stromal keratocytes were viable in the GelMA and GelMA-HEMA hydrogels as calculated by Live-Dead Assay and NIH Image-J program. Cells synthesized representative collagens and proteoglycans in the hydrogels indicating that they preserved their keratocyte functions. Transparency of the cell loaded GelMA-HEMA hydrogels was increased significantly up to 90% at 700 nm during three weeks of incubation and was comparable with the transparency of native cornea. Cell loaded GelMA-HEMA corneal stroma model is novel and reported for the first time in the literature in terms of introduction of cells during the preparation phase of the hydrogels. The appropriate mechanical strength and high transparency of the cell loaded constructs indicates a viable alternative to the current devices used in the treatment of corneal blindness.
TL;DR: This study demonstrates that the GelMA hydrogels-encapsulated hPDLSCs have a significant alveolar regenerative potential, and may represent a new strategy for the therapy ofAlveolar bone defects.
Abstract: Although various efforts have been made to develop effective treatments for alveolar bone defect, alveolar regeneration has been emerging as the one with the most potential Herein, we investigated the potential of gelatin methacrylate (GelMA) hydrogels-encapsulated human periodontal ligament stem cells (hPDLSCs) to regenerate alveolar bone. The easy, rapid, and cost-effective nature of GelMA hydrogels makes them a promising mode of stem cell-delivery for clinically relevant alveolar bone regeneration. More importantly, GelMA hydrogels provide an optimal niche for hPDLSCs proliferation, migration and osteogenic differentiation, which are critical for alveolar bone regeneration. In this study, we examined the microstructure of GelMA hydrogels, and identified a highly porous and interconnected network. Compressive test of GelMA hydrogels showed that the stress reached a maximum value of 13.67 ± 0.03 kPa when the strain reached 55%. The maximum values of swelling ratio were 700 ± 47% at the fifth hour. The proliferation rate of hPDLSCs in the GelMA hydrogels resembled that in 2D culture and gradually increased. We established a critical-sized rat model of alveolar bone defects, and applied Micro-CT to assess new bone formation. Compared to the control group, there was substantial bone regeneration in the GelMA + hPDLSCs group at both 4 and 8 weeks after the operation. Histological analysis results were consistent with Micro-CT results. Our study demonstrates that the GelMA hydrogels-encapsulated hPDLSCs have a significant alveolar regenerative potential, and may represent a new strategy for the therapy of alveolar bone defects.
TL;DR: Biocompatibility studies were conducted in vitro, which revealed the non-cytotoxic nature of the material and demonstrated the potential of the hydrogel based on dialdehyde galactomannan and N-succinyl chitosan for cell culture and soft tissue engineering.
Abstract: Regenerative medicine proposes to regenerate or even replace human damaged tissues to return to normal functions. Hence, biomaterials have been used to provide appropriate environment for cell development. Among the groups of biodegradable biomaterials, hydrogels, which are characterized by three-dimensional and cross-linked networks of water-soluble polymers, have been highlighted as suitable matrices for such applications. An injectable hydrogel based on oxidized galactomannan (OxGM) from Delonix regia and N-succinyl chitosan (NSC) was developed and characterized according to its physicochemical and biocompatible properties. The hydrogel was formed by Schiff base (−CH = N−) cross-linking between aldehyde groups from OxGM and NH2 groups from NSC, in few minutes (9.7 min) without any external stimulus. A hydrogel with macroporous structure, interconnected pores, and porosity of 69% was obtained. The biomaterial exhibited excellent injectability. No change in volume or integrity was observed in the hydrogel after its swelling in phosphate buffered saline (PBS) medium. This is an important property because when the hydrogel is injected into the site of interest and it fills the environment, it will not have additional space to occupy. Biocompatibility studies were conducted in vitro, which revealed the non-cytotoxic nature of the material and demonstrated the potential of the hydrogel based on dialdehyde galactomannan and N-succinyl chitosan for cell culture and soft tissue engineering.
TL;DR: The results reveal that the irregular nano-porous of PEEK affect the biological properties, and high-temperature hydrothermal NP treatment induced early osteogenic differentiation and early osteogenesis.
Abstract: Polyether-ether-ketone (PEEK) is becoming a popular component of clinical spinal and orthopedic applications, but its practical use suffers from several limitations. In this study, irregular nano-porous monolayer with differently functional groups was formed on the surface of PEEK through sulfonation and nitrification. The surface characteristics were detected by field-emission scanning electron microscopy, atomic force microscopy, energy-dispersive X-ray spectrometry, water contact angle measurements and Fourier transform infrared spectroscopy. In vitro cellular behaviors were evaluated by cell adhesion, morphological changes, proliferation, alkalinity, phosphatase activity, real-time RT-PCR and western blot analyses. In vivo osseointegration was examined through micro-CT and histological assessments. Our results reveal that the irregular nano-porous of PEEK affect the biological properties. High-temperature hydrothermal NP treatment induced early osteogenic differentiation and early osteogenesis. Modification by sulfonation and nitrification can broaden the use of PEEK in orthopedic and dental applications. This study provides a theoretical basis for the wider clinical application of PEEK. a To obtain a uniform porous structure, PEEK samples were treated by concentrated sulfuric acid and fuming nitric acid (82-80%) with magnetic stirring sequentially. b Effects of nanopores on biological behavior of bMSCS.
TL;DR: The fabrication of polylactic acid/hydroxyapatite (PLA/HA) composite nanofibrous scaffolds via phase separation method to mimic the native extracellular matrix (ECM) is reported, which showed that the addition of HA dramatically impacted the morphology of the PLA matrix, which changed from 3D nan ofibrous network structure to a disorderly micro-nanofIBrous porous structure.
Abstract: Combining synthetic polymer scaffolds with inorganic bioactive factors is widely used to promote the bioactivity and bone conductivity of bone tissue. However, except for the chemical composition of scaffold, the biomimetic structure also plays an important role in its application. In this study, we report the fabrication of polylactic acid/hydroxyapatite (PLA/HA) composite nanofibrous scaffolds via phase separation method to mimic the native extracellular matrix (ECM). The SEM analysis showed that the addition of HA dramatically impacted the morphology of the PLA matrix, which changed from 3D nanofibrous network structure to a disorderly micro-nanofibrous porous structure. At the same time, HA particles could be evenly dispersed at the end of the fiber. The FTIR and XRD demonstrated that there was not any chemical interaction between PLA and HA. Thermal analyses showed that HA could decrease the crystallization of PLA, but improve the thermal decomposition temperature of the composite scaffold. Moreover, water contact angle analysis of the PLA/HA composite scaffold demonstrated that the hydrophilicity increased with the addition of HA. Furthermore, apatite-formation ability tests confirmed that HA could not only more and faster induced the deposition of weak hydroxyapatite but also induced specific morphology of HA.
TL;DR: By implanting this membrane to the damagedperiodontal tissue, bone regeneration will take place and integrity of periodontal tissues will be preserved, and the barrier membrane developed here is biodegradable and can be easily manipulated, has osteogenic activity and inactivity for epithelial cells.
Abstract: In the present study, a chitosan-based, multifunctional and double-faced barrier membrane was developed for the periodontitis therapy. The porous surface of the membrane was coated with bone-like hydroxyapatite (HA) produced by microwave-assisted biomimetic method and enriched with bone morphogenetic factor 6 (BMP-6) to enhance the bioactivity of chitosan. This surface of the membrane was designed to be in contact with the hard tissue that was damaged due to periodontitis. Otherwise the nonporous surface of membrane, which is in contact with the inflammatory soft tissue, was coated with electrospun polycaprolactone (PCL) fibers to prevent the migration of epithelial cells to the defect area. PrestoBlue, Scanning Electron Microscope (SEM) and real-time PCR results demonstrated that while porous surface of the membrane was enhancing the proliferation and differentiation of MC3T3-E1 preosteoblasts, nonporous surface of membrane did not allow migration of epithelial Madine Darby Bovine Kidney (MDBK) cells. The barrier membrane developed here is biodegradable and can be easily manipulated, has osteogenic activity and inactivity for epithelial cells. Thus, by implanting this membrane to the damaged periodontal tissue, bone regeneration will take place and integrity of periodontal tissues will be preserved.
TL;DR: Results hint at a possible application of high payload liposomes for improved topical dermal accumulations of actives and congruent with ex vivo skin penetration/permeation results, which showed how more deformable liposome showed an improved deposition in the epidermis.
Abstract: This work describes the development of liposomes encapsulating curcumin (CURC) aiming to provide insights on the influence of CURC on the thermodynamic and skin permeation/penetration features of the vesicles. CURC-loaded liposomes were prepared by hydration of lipid film, in the 0.1–15% CURC:DPPC w/w ratio range. The obtained formulations were characterized for their size distribution, zeta potential and vesicle deformability, along with their thermodynamic properties and ex vivo skin penetration/permeation ability. Liposome size was 110–130 nm for all formulations, with fairly narrow size distribution (polydispersity index was ≤0.20) and a zeta potential mildly decreasing with CURC loading. DSC outcomes indicated that CURC interferes with the packing of DPPC acyl chains in liposome bilayer when CURC percentage was at least 10%, leading to a more fluid state than blank and low-payload vesicles. Consistently, the deformability index of liposomes with 15% CURC:DPPC was strongly increased compared to other formulations. This is congruent with ex vivo skin penetration/permeation results, which showed how more deformable liposomes showed an improved deposition in the epidermis, which acts as a reservoir for the active molecule. Altogether, results hint at a possible application of high payload liposomes for improved topical dermal accumulations of actives.
TL;DR: An alginate/chitosan membrane sufficiently stable in a simulated vaginal fluid and able to dissolve over time at a very slow and linear rate is developed and represents a promising drug delivery system for local intravaginal applications.
Abstract: The intravaginal route of administration can be exploited to treat local diseases and for systemic delivery. In this work, we developed an alginate/chitosan membrane sufficiently stable in a simulated vaginal fluid and able to dissolve over time at a very slow and linear rate. The membrane demonstrated good mechanical properties both in its swollen and dry form. As a study case, we evaluated the viability of this potential drug delivery system for the treatment of bacterial vaginosis, a common disease affecting women in their reproductive age. Metronidazole was effectively included in the alginate/chitosan membrane and its bactericide effect was demonstrated against Staphylococcus aureus and Gardnerella vaginalis, simultaneously showing good biocompatibility with a cervix epithelial cell line. Since this alginate/chitosan membrane is stable in a simulated vaginal environment, is easy to fabricate and can be used for the controlled release of a model drug, it represents a promising drug delivery system for local intravaginal applications.
TL;DR: It is suggested that AFG has great promise for rapidly directing axonal regrowth for nerve regeneration and contributed to significantly improved recovery of motor functional behavior of SCI canines with AFG implantation.
Abstract: Spinal cord injuries (SCI) normally disrupt the long axonal tracts of the spinal cord and cause permanent neurological deficits, for which there is currently a lack of effective therapeutic methods. Biomaterial-based regenerative medicine is a pivotal strategy to induce axonal regeneration through delivery of biophysical and/or biochemical regulatory cues by biomaterials. We previously fabricated a hierarchically aligned fibrin hydrogel (AFG) that could promote neurogenic differentiation of stem cells in vitro and has been successfully applied for peripheral nerve and spinal cord regeneration in rats. In this study, AFG was used to repair a canine lumbar segment 2 hemisection spinal cord injury, and the consistency of histological, imageological and behavioral results was compared. AFG was used to construct an aligned fiber bridge that supported cell adhesion in vitro and rapidly facilitated tissue invasion along the long axis of fibers in vivo, Moreover, in vivo results demonstrated regrowth of axons in an oriented pattern connecting the rostral and caudal stumps. Consistent results were confirmed by diffusion tensor imaging, which allowed successful tracing of reconnected nerve fibers across the defect. As a result, directional axonal regrowth contributed to significantly improved recovery of motor functional behavior of SCI canines with AFG implantation. Our results suggest that AFG has great promise for rapidly directing axonal regrowth for nerve regeneration.
TL;DR: Results showed a reduced number of brain cysts, high levels of serum Toxo IgG, and normal histo-morphology with preserved parenchymal, and stromal tissues in rats groups treated with curcumin and Curcumin@MOFs nanocomposite.
Abstract: Toxoplasmosis is a zoonotic protozoal disease caused by Toxoplasma gondii, an intracellular opportunistic protozoan parasite that can infect any warm-blooded vertebrate cell. In this study, zirconium, and iron-based metal-organic framework was prepared according to the solvothermal method. New nanocomposite (Curcumin@MOFs) was prepared by reacting curcumin with amino-functionalized metal-organic frameworks (Fe-MOF and UiO-66-NH2). Besides characterizations of the composite by powder X-ray diffraction and scanning electron microscope, nano-Curcumin@MOFs was used as a new novel structure as atrial for treatment of chronic toxoplasmosis. Results showed a reduced number of brain cysts, high levels of serum Toxo IgG, and normal histo-morphology with preserved parenchymal, and stromal tissues in rats groups treated with curcumin and Curcumin@MOFs nanocomposite.
TL;DR: In vivo experiments showed the ability of these implanted curcumin loaded nanofibers to mitigate endometriosis, with a considerable reduction in the endometrial glands and stroma, along with significant reduction in infiltration of inflammatory cells.
Abstract: Endometriosis is a common, chronic gynecological disorder associated with ongoing pelvic pain, infertility, and adhesions in reproductive age women. Current therapeutic strategies are not effective and the recurrent nature of endometriosis makes it difficult to treat. In this study, we have designed a drug delivery system to control sustained and prolonged release of curcumin in the peritoneum and pelvic cavity of a mouse model of endometriosis. Poly e-Caprolactone (PCL) and poly ethylene glycol (PEG) polymers were used to synthesize curcumin loaded nanofibers. After scanning electron microscopy (SEM) observation of the nanofiber’s morphology, we evaluated the drug release profile and in vitro degradation rate of the curcumin-loaded nanofibers. Next, we tested these nanofibers in vivo in the peritoneum of an endometriosis mouse model to determine their anti-endometriosis effects. Histological evaluations were also performed. Curcumin loaded nanofibers were successfully synthesized in the 8 and 10 wt% polymers. The release test of the curcumin-loaded nanofibers showed that approximately 23% of the loaded curcumin was released during 30 min, 35% at 24 h, and 50% at 30 days. Endometriosis was successfully induced in Balb/c mice, as noted by the observed characteristics of endometriosis in all of the mice and confirmation of endometriosis by hematoxylin and eosin (H&E) staining. In vivo experiments showed the ability of these implanted curcumin loaded nanofibers to mitigate endometriosis. We observed a considerable reduction in the endometrial glands and stroma, along with significant reduction in infiltration of inflammatory cells. Implantable curcumin loaded nanofibers successfully mitigated intraperitoneal endometriosis.
TL;DR: In this paper, an in vivo study in sheep was carried out with the aim of assessing the bone response and the trend of osteointegration of a randomized trabecular titanium structure produced by the additive manufacturing technique.
Abstract: The additive manufacturing techniques (AM) are able to realize three-dimensional trabecular structures that mimic the trabecular structure of the bone. An in vivo study in sheep was carried out with the aim of assessing the bone response and the trend of osteointegration of a randomized trabecular titanium structure produced by the AM technique. In 6 sheep were implanted 84 specimens with a trabecular titanium structure (4 implants in the femur distal epiphysis; 4 implants in the tibial plate; 6 implants in the tibial shaft). Sheep were sacrificed at 3 postoperative time-points: 6 weeks, 10 weeks, 14 weeks. Histomorphometric analysis was performed for the evaluation of Bone Implant Contact, and Bone Ingrowth. A standard push-out test was used to analyze the mechanical characteristics of the bone-implant interface. The histomorphometric data and biomechanical tests showed a fast osseointegration of the specimens both in the cancellous and in the cortical bone. The quantitative analysis of osseointegration data in cancellous bone showed the percentage of the surface of the implant in direct contact with the regenerated bone matrix significantly improved from 28% at 6 weeks to 54% at 14 weeks. An early osseointegration occurred in cortical bone showing that 75% of surface of implant was in direct contact with regenerated bone after 6 weeks; this value increased to 85% after 14 weeks. Mechanical tests revealed an early improvement of mean peak load of implants at 10 weeks (4486 N ± 528 N) compared to values at 6 weeks (2516 N ± 910 N) confirming the high rate of progression of osseointegration in the cortical bone. The non-mineralized matrix followed an increasing process of mineralization almost completely after 14 weeks. The results of this study have showed a rapid osseointegration and excellent biocompatibility for a randomized trabecular titanium structure that should be confirmed by clinical investigations.
TL;DR: It is concluded that meticulous customized design 3D printed micro-porous prosthesis combined with intramedullary nail may be a promising and an alternative strategy to treat metaphyseal segmental irregular-shaped femoral bone defect, especially for cases with massive juxta-articular bone loss.
Abstract: Five patients with segmental irregular-shaped bone defect of the femur were recruited in this study from 2017.12 to 2018.11. All patients were treated by customized design and 3D printed micro-porous prosthesis. And the procedure was divided into stages: radical debridement and temporary fixation (the first stage); the membrane formation and virtual surgery (intervening period for 6-8 weeks); definite reconstruction the defects (the second stage). Routine clinical follow-up and radiographic evaluation were done to assess bone incorporation and complications of internal fixation. The weight-bearing time and the joint function of the patients were recorded. The patients were followed up for an average of 16.4 months. The average length of bone defect and the distal residual bone was 12 cm and 6.5 cm. The average time of partial weight-bearing and full weight-bearing was 12.7 days and 2.6 months. X-ray demonstrated good osseous integration of the implant/bone interface. No complications occurred such as implant loosening, subsidence, loss of correction and infection. At the last follow-up, Harris score of hip joint was excellent in 2 cases, good in 2 cases, fair in 1 case; HSS score of knee joint was good in 4 cases, middle in 1 case. From our study, we concluded that meticulous customized design 3D printed micro-porous prosthesis combined with intramedullary nail may be a promising and an alternative strategy to treat metaphyseal segmental irregular-shaped femoral bone defect, especially for cases with massive juxta-articular bone loss.
TL;DR: Two micron-sized hydroxyapatites were investigated for electrospinning with PLA at various contents to examine the effect of polymer concentration, filler type and filler concentration on the morphology of the scaffolds, in addition to the mechanical properties and bioactivity.
Abstract: HA-mineralised composite electrospun scaffolds have been introduced for bone regeneration due to their ability to mimic both morphological features and chemical composition of natural bone ECM. Micro-sized HA is generally avoided in electrospinning due to its reduced bioactivity compared to nano-sized HA due to the lower surface area. However, the high surface area of nanoparticles provides a very high surface energy, leading to agglomeration. Thus, the probability of nanoparticles clumping leading to premature mechanical failure is higher than for microparticles at higher filler content. In this study, two micron-sized hydroxyapatites were investigated for electrospinning with PLA at various contents, namely spray dried HA (HA1) and sintered HA (HA2) particles to examine the effect of polymer concentration, filler type and filler concentration on the morphology of the scaffolds, in addition to the mechanical properties and bioactivity. SEM results showed that fibre diameter and surface roughness of 15 and 20 wt% PLA fibres were significantly affected by incorporation of either HA. The apatite precipitation rates for HA1 and HA2-filled scaffolds immersed in simulated body fluid (SBF) were similar, however, it was affected by the fibre diameter and the presence of HA particles on the fibre surface. Degradation rates of HA2-filled scaffolds in vitro over 14 days was lower than for HA1-filled scaffolds due to enhanced dispersion of HA2 within PLA matrix and reduced cavities in PLA/HA2 interface. Finally, increasing filler surface area led to enhanced thermal stability as it reduced thermal degradation of the polymer.
TL;DR: The development of Ti-25Ta alloys as a base material, in which was introduced zirconium, with concentration varying between 0 and 40 wt%, with the aim of biomedical applications, and the cytotoxicity test showed that the extracts of studied alloys are not cytotoxic for osteoblast cells in short periods of culture.
Abstract: Titanium alloys have been widely used as biomaterials, especially for orthopedic prostheses and dental implants, but these materials have Young's modulus almost three times greater than human cortical bones. Because of this, new alloys are being produced for the propose of decreasing Young's modulus to achieve a more balanced mechanical compatibility with the bone. In this paper, it is reported the development of Ti-25Ta alloys as a base material, in which was introduced zirconium, with concentration varying between 0 and 40 wt%, with the aim of biomedical applications. The alloys were prepared in an arc-melting furnace. The microstructural analysis was performed by x-ray diffraction as well as optical and scanning electron microscopy. Selected mechanical properties were analyzed by microhardness and Young’s modulus measurements, and cytotoxicity analysis by indirect test. X-ray measurements revealed the presence of α″ phase in the alloy without zirconium; α″ + β phases for alloys with 10, 20, and 30 wt% of zirconium, and β phase only for the alloy with 40 wt% of zirconium. These results were corroborated by the microscopy results. The hardness of the alloy was higher than that of cp-Ti due to the actions of zirconium and tantalum as hardening agents. The Young’s modulus decreases with high levels of zirconium due to the stabilization of the β phase. The cytotoxicity test showed that the extracts of studied alloys are not cytotoxic for osteoblast cells in short periods of culture.
TL;DR: The results indicated that SA crosslinking after 3D printing anchored different materials together and integrated all regions, while the mechanical strength including the interface adhesion strength between layers were characterized.
Abstract: Osteochondral defects affect both of cartilage and subchondral areas, thus it poses a significant challenge to simultaneously regenerate two parts in orthopedics. Tissue engineering strategy is currently regarded as the most promising way to repair osteochondral defects. This study focuses on developing a multilayered scaffold with enhanced interface bonding through 3D printing. One-shot printing process enables control over material composition, pore structure, and size in each region of the scaffold, while realizes seamlessly integrated construct as well. The scaffold was designed to be triphasic: a porous bone layer composed of alginate sodium (SA) and mesoporous bioactive glasses (MBG), an intermediate dense layer also composed of SA and MBG and a cartilaginous layer composed of SA. The mechanical strength including the interface adhesion strength between layers were characterized. The results indicated that SA crosslinking after 3D printing anchored different materials together and integrated all regions. Additional scaffold soaking in simulated body fluid (SBF) and cell culture medium induced apatite deposition and had weakened the compressive and tensile strengths, while no layer dislocation or delamination occurred.
TL;DR: The combination of NaSi and CaP glasses has favorable setting behavior, sealing ability, and mature phases for pulp capping while relying on a relatively simple, inorganic composition.
Abstract: Evaluation of the physicochemical behavior and setting reactions of a novel inorganic pulp capping cement which makes use of the unique corrosion properties of sodium metasilicate (NaSi) glass. NaSi and calcium phosphate (CaP) glass powders were synthesized through a melt-quench method. Cements were created by mixing various amounts of the glasses with deionized water at a powder-to-liquid ratio of 2.5 g mL−1. Working and setting times were measured using the indentation standard ISO 9917-1. Sealing ability was tested by placing set samples of each composition in methylene blue dye solution for 24 h. Set samples were also submerged in phosphate buffered saline and incubated at 37 °C for one week. X-ray diffraction was used to identify mature crystalline phases after incubation. Infrared spectroscopy and scanning electron microscopy were used to characterize cements before and after setting and after incubation. Working and setting times measured in the ranges of 2–5 and 10–25 min, respectively. Working and setting time generally decrease with increased NaSi concentration. Cements with compositions of 25 and 33 wt% NaSi were found to resist the infiltration of dye and maintain their shape. Compositions outside this range absorbed dye and collapsed. Infrared spectroscopy provided insight into the setting mechanism of these cements. After one week in vitro, cements were found to contain crystalline phases matching chemically stable, bioactive phases. The combination of NaSi and CaP glasses has favorable setting behavior, sealing ability, and mature phases for pulp capping while relying on a relatively simple, inorganic composition.