Degradation Profile Research Articles

Degradation Behavior of Biodegradable Plastics in Thermophilic Landfill Soil and Wastewater Sludge Conditions

In this study, three common biodegradable plastics, namely, poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), poly(butylene succinate) (PBS) and poly(butylene adipate-co-terephthalate) (PBAT) were all buried in a mixture of landfill soil and wastewater sludge and incubated under thermophilic (61°C) oxygen-limited conditions. At the end of the 90-day test, the degradation ranking order was PHBV > PBS > PBAT. Only PHBV was completely degraded over the 60 days, while PBS and PBAT displayed 24.04% ± 3.37% and 18.26% ± 3.77% weight loss, respectively. The differences in the degradation and disintegration profiles among these materials were observed. The results showed that PHBV lost its thickness and degraded from the edges of the specimens. Both PBS and PBAT were reduced into small fragile fragments during the degradation process. SEM micrographs revealed that irregular roughness with many holes and cracks was characteristic of PHBV, while slightly smooth surfaces were found on PBS and PBAT. All the materials showed continuous decreases in the thermal stability and the percentage of carbon content in the molecular structures after the degradation test. Fourier transform infrared (FTIR) spectroscopy revealed that the chemical structure of PHBV was changed during the biodegradation test, while both PBS and PBAT were unchanged under the same test conditions. However, the peak for carboxylate ions was found after the degradation of all the samples. Having a deep understanding of the degradability behavior can contribute to the development of biodegradable plastic waste management in the future.

Cytoskeletal protein degradation in brain death donor kidneys associates with adverse posttransplant outcomes

In brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys adversely impacting the quality of grafts. Here, we hypothesized that donation after brain death (DBD) kidneys undergo proteolytic processes that may deem grafts susceptible to posttransplant dysfunction. Using mass spectrometry and immunoblotting, we mapped degradation profiles of cytoskeletal proteins in deceased and living donor kidney biopsies. We found that key cytoskeletal proteins in DBD kidneys were proteolytically cleaved, generating peptide fragments, predominantly in grafts with suboptimal posttransplant function. Interestingly, α‐actinin‐4 and talin‐1 proteolytic fragments were detected in brain death but not in circulatory death or living donor kidneys with similar donor characteristics. As talin‐1 is a specific proteolytic target of calpain‐1, we investigated a potential trigger of calpain activation and talin‐1 degradation using human ex vivo precision‐cut kidney slices and in vitro podocytes. Notably, we showed that activation of calpain‐1 by transforming growth factor‐β generated proteolytic fragments of talin‐1 that matched the degradation fragments detected in DBD preimplantation kidneys, also causing dysregulation of the actin cytoskeleton in human podocytes; events that were reversed by calpain‐1 inhibition. Our data provide initial evidence that brain death donor kidneys are more susceptible to cytoskeletal protein degradation. Correlation to posttransplant outcomes may be established by future studies.

In Vitro Hydrolytic Degradation of Polyester-Based Scaffolds under Static and Dynamic Conditions in a Customized Perfusion Bioreactor.

Creating biofunctional artificial scaffolds could potentially meet the demand of patients suffering from bone defects without having to rely on donors or autologous transplantation. Three-dimensional (3D) printing has emerged as a promising tool to fabricate, by computer design, biodegradable polymeric scaffolds with high precision and accuracy, using patient-specific anatomical data. Achieving controlled degradation profiles of 3D printed polymeric scaffolds is an essential feature to consider to match them with the tissue regeneration rate. Thus, achieving a thorough characterization of the biomaterial degradation kinetics in physiological conditions is needed. Here, 50:50 blends made of poly(-caprolactone)–Poly(D,L-lactic-co-glycolic acid (PCL-PLGA) were used to fabricate cylindrical scaffolds by 3D printing (⌀ 7 × 2 mm). Their hydrolytic degradation under static and dynamic conditions was characterized and quantified. For this purpose, we designed and in-house fabricated a customized bioreactor. Several techniques were used to characterize the degradation of the parent polymers: X-ray Photoelectron Spectroscopy (XPS), Gel Permeation Chromatography (GPC), Scanning Electron Microscopy (SEM), evaluation of the mechanical properties, weigh loss measurements as well as the monitoring of the degradation media pH. Our results showed that flow perfusion is critical in the degradation process of PCL-PLGA based scaffolds implying an accelerated hydrolysis compared to the ones studied under static conditions, and up to 4 weeks are needed to observe significant degradation in polyester scaffolds of this size and chemical composition. Our degradation study and characterization methodology are relevant for an accurate design and to tailor the physicochemical properties of polyester-based scaffolds for bone tissue engineering.

Bioinspired Silk Fibroin-Based Composite Grafts as Bone Tunnel Fillers for Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) replacement is still a big challenge in orthopedics due to the need to develop bioinspired implants that can mimic the complexity of bone-ligament interface. In this study, we propose biomimetic composite tubular grafts (CTGs) made of horseradish peroxidase (HRP)-cross-linked silk fibroin (SF) hydrogels containing ZnSr-doped β-tricalcium phosphate (ZnSr-β-TCP) particles, as promising bone tunnel fillers to be used in ACL grafts (ACLGs) implantation. For comparative purposes, plain HRP-cross-linked SF hydrogels (PTGs) were fabricated. Sonication and freeze-drying methodologies capable of inducing crystalline β-sheet conformation were carried out to produce both the CTGs and PTGs. A homogeneous microstructure was achieved from microporous to nanoporous scales. The mechanical properties were dependent on the inorganic powder’s incorporation, with a superior tensile modulus observed on the CTGs (12.05 ± 1.03 MPa) as compared to the PTGs (5.30 ± 0.93 MPa). The CTGs presented adequate swelling properties to fill the space in the bone structure after bone tunnel enlargement and provide a stable degradation profile under low concentration of protease XIV. The in vitro studies revealed that SaOs-2 cells adhered, proliferated and remained viable when cultured into the CTGs. In addition, the bioactive CTGs supported the osteogenic activity of cells in terms of alkaline phosphatase (ALP) production, activity, and relative gene expression of osteogenic-related markers. Therefore, this study is the first evidence that the developed CTGs hold adequate structural, chemical, and biological properties to be used as bone tunnel fillers capable of connecting to the ACL tissue while stimulating bone tissue regeneration for a faster osteointegration.

Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability. However, some excipients are prone to degradation during repeated use and/or improper storage, and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored, affecting the stability of biopharmaceuticals. In this study, we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry (GC-MS). The other polyol excipient, mannitol, was much more stable than glycerol. The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide, thymopentin, were also evaluated. The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol, compared to 95.8% in other formulations after the stress test. Most glycerol impurities (i.e., aldehydes and ketones) reacted with thymopentin, affecting the stability of thymopentin formulations. In conclusion, this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage. Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

A comprehensive study to identify and characterize major degradation products of Ivermectin drug substance including its degradation pathways using LC-HRMS and NMR

Ivermectin (IVM) drug substance is a semi-synthetic macrocyclic lactone that exhibits a broad spectrum of activity and high potency towards endo- and ectoparasites. In this study, a comprehensive forced degradation study was carried out on IVM drug substance (under the conditions recommended in the ICH guidelines) to identify and characterize its major degradation products (DPs). IVM drug substance was subjected to acidic, alkaline, oxidation (H2O2 and K2Cr2O7), thermal (solid and solution state), and photolytic (solid and solution state) stress degradations. Chromatographic separation of the drug substance and its DPs was achieved using a gradient elution on a HALO C18 column (150 × 4.6 mm, 2.7 µm). A total of five major DPs were observed for IVM drug substance under various stressed conditions. Additionally, ivermectin API lots exhibited instability when stored under room temperature and at 45% relative humidity for two years. These DPs were identified and characterized using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and a comparison of their fragmentation profile with IVM H2B1a using tandem mass spectrometry. Of these, H2O2 induced oxidative degradation product (3,4-epoxide H2B1a) was isolated using semi-preparative HPLC and its structure was elucidated comprehensively using LC-HRMS and nuclear magnetic resonance spectroscopy. The proposed structures of the DPs have been rationalized by appropriate degradation pathways of IVM H2B1a. Comprehensive degradation profile of IVM drug substance should facilitate the understanding of the stability profile of IVM drug substance, setting the specification of DPs in finished products as well as aid in the design of generic formulation made with IVM.

Biodegradation Kinetic Study of Cassava & Tannia Starch-Based Bioplastics as Green Material in Various Media

The rate of biodegradation of cassava – tannia starch bioplastic in various media was evaluated. Bioplastic degradation profile for a period of 4 weeks was seen following the Hills Equation where the speed of bioplastic biodegradation in sand media had higher yields than farm soil and compost media with the value up to 98.84 %. This is also proven by measuring the rate of degradation reaction using a first order reaction rate, where the value of the constant rate of reaction from bioplastics in sand is a little bit higher compared to farm soil and compost media (0.77647, 0.67133, and 0.15779 week-1, respectively). According to SEM pictures, there were numerous bacteria (either aerobic or anaerobic) and fungal species on the bioplastic surface, which have a role in the biodegradability of the polymer in bioplastics. The FTIR spectra of bioplastic biodegradation showed a decrease in the peak at 3400 - 3200 cm-1, and loss of the peak was present in the control at 2900 cm-1 which showed a breakdown of the polymer chain in the bioplastic especially in the O-H and C-H bonds, respectively. It can be concluded that farm soil and sand are the most optimal media in the bioplastic biodegradation process, while compost has potential but its maturity must be considered.

3D Printing of Polymeric Bioresorbable Stents: A Strategy to Improve Both Cellular Compatibility and Mechanical Properties.

One of the leading causes of death is cardiovascular disease, and the most common cardiovascular disease is coronary artery disease. Percutaneous coronary intervention and vascular stents have emerged as a solution to treat coronary artery disease. Nowadays, several types of vascular stents share the same purpose: to reduce the percentage of restenosis, thrombosis, and neointimal hyperplasia and supply mechanical support to the blood vessels. Despite the numerous efforts to create an ideal stent, there is no coronary stent that simultaneously presents the appropriate cellular compatibility and mechanical properties to avoid stent collapse and failure. One of the emerging approaches to solve these problems is improving the mechanical performance of polymeric bioresorbable stents produced through additive manufacturing. Although there have been numerous studies in this field, normalized control parameters for 3D-printed polymeric vascular stents fabrication are absent. The present paper aims to present an overview of the current types of stents and the main polymeric materials used to fabricate the bioresorbable vascular stents. Furthermore, a detailed description of the printing parameters’ influence on the mechanical performance and degradation profile of polymeric bioresorbable stents is presented.

A Comparative Study of Two Bone Graft Substitutes-InterOss® Collagen and OCS-B Collagen®.

Bone is a complex hierarchical tissue composed of organic and inorganic materials that provide structure, support, and protection to organs. However, there are some critical size defects that are unable to regenerate on their own and therefore require clinical repair. Bone graft substitutes allow repair by providing a temporary resorbable device. Among the common filler materials that aid in regeneration is hydroxyapatite particles of either animal or human origin which is used to fill or reconstruct periodontal and bony defects in the mouth. However, particulate graft substitutes suffer from localized migration away from the implantation site, necessitating the use of a barrier membrane. In this study, we designed InterOss Collagen, combining bovine hydroxyapatite granules with porcine-skin derived collagen to form a bone filler composite. Physiochemical properties of InterOss Collagen and a commercially available product, OsteoConductive Substitute-Bovine (OCS-B) Collagen, referred to as OCS-B Collagen, were examined. We found two bone graft substitutes to be mostly similar, though InterOss Collagen showed comparatively higher surface area and porosity. We conducted an in vivo study in rabbits to evaluate local tissue responses, percent material resorption and bone formation and showed that the two materials exhibited similar degradation profiles, inflammatory and healing responses following implantation. Based on these results, InterOss Collagen is a promising dental bone grafting material for periodontal and maxillofacial surgeries.

Removal of organic contaminants from flowback water using Fenton process

Shale gas exploration requires large amount of water along with the additives for hydraulic fracturing to facilitate the extraction of natural gas. This water contains significant amount of inorganic and organic pollutants and needs to be treated before disposal. Advanced oxidation process (AOP) like Fenton can be used for removal of organics from the flowback water. In this study, Fenton process was applied to treat real life flowback water (after pretreatment) to investigate its efficacy to degrade the organics. The effects of various parameters like initial solution pH, the dose of Fenton reagents were investigated in detail. A detailed kinetic model was developed by considering various reactions involved in the process. The set of model equations were solved numerically and unknown rate constants were evaluated by optimization of degradation profile of the organics. The pH profile was also accurately predicted during the reaction. The model can be of help to design engineers to upscale such system.

QbD Approached in Method Development, Validation and Degradation Profiling of Aripiprazole a Antidepressent Agent

The aim of present research work was to develop simple, precise and rapid RP-HPLC method for analysis of Aripiprazole in tablet dosage form using QbD Method. RP-HPLC method was developed for the estimation of Aripiprazole in tablet dosage form with the help of QbD approaches. The proposed methods were applied for the determination of drug in tablet dosage form. In this method concentration of each drug was obtained by using the absorptivity values calculated for drug wavelength 254nm and solving the equation. A rapid and reliable RP-HPLC method was developed and validated estimation of Aripiprazole in tablet dosage form. The RP-HPLC method was performed C18 (100mm x 4.6 mm,)2.5 μm particle size in gradient mode, and the sample was analyzed using methanol 80 ml and 20 ml (pH 3.3 0.05% OPA with TEA) as a mobile phase at a flow rate of 0.7 ml/min and detection at nm. By the retention time for Aripiprazole found 3.29 min respectively. The method was applied to marketed tablet formulations. The tablet assay was performed for combination was validated for accuracy, precision, linearity, specificity, and sensitivity in accordance with ICH guidelines. Validation related the method is specific, rapid, accurate, precise, reliable, and reproducible. Calibration plots by both HPLC were linear over the 10-50μg/ml for Aripiprazole respectively, and recoveries from tablet dosage form were between 99.48 and 100.02 %. The method can be used for routine of the quality control in pharmaceuticals. The RP-HPLC method was found to be simple, economical and rapid as compared to MS method was found to be more accurate, precise and robust. Both these methods can be used for routine analysis of Aripiprazole in tablet dosage form.

Cell-Seeded Biomaterial Scaffolds: The Urgent Need for Unanswered Accelerated Angiogenesis.

One of the most arduous challenges in tissue engineering is neovascularization, without which there is a lack of nutrients delivered to a target tissue. Angiogenesis should be completed at an optimal density and within an appropriate period of time to prevent cell necrosis. Failure to meet this challenge brings about poor functionality for the tissue in comparison with the native tissue, extensively reducing cell viability. Prior studies devoted to angiogenesis have provided researchers with some biomaterial scaffolds and cell choices for angiogenesis. For example, while most current angiogenesis approaches require a variety of stimulatory factors ranging from biomechanical to biomolecular to cellular, some other promising stimulatory factors have been underdeveloped (such as electrical, topographical, and magnetic). When it comes to choosing biomaterial scaffolds in tissue engineering for angiogenesis, key traits rush to mind including biocompatibility, appropriate physical and mechanical properties (adhesion strength, shear stress, and malleability), as well as identifying the appropriate biomaterial in terms of stability and degradation profile, all of which may leave essential trace materials behind adversely influencing angiogenesis. Nevertheless, the selection of the best biomaterial and cells still remains an area of hot dispute as such previous studies have not sufficiently classified, integrated, or compared approaches. To address the aforementioned need, this review article summarizes a variety of natural and synthetic scaffolds including hydrogels that support angiogenesis. Furthermore, we review a variety of cell sources utilized for cell seeding and influential factors used for angiogenesis with a concentrated focus on biomechanical factors, with unique stimulatory factors. Lastly, we provide a bottom-to-up overview of angiogenic biomaterials and cell selection, highlighting parameters that need to be addressed in future studies.

Gaussian process-based prognostics of lithium-ion batteries and design optimization of cathode active materials

The increasing adoption of lithium-ion batteries (LIBs) in consumer electronics, electric vehicles, and smart grids poses two challenges: the accurate prediction of the battery health to prevent operational impairments and the development of new materials for high-performance LIBs. Characterized by their flexibility and mathematical tractability, Gaussian processes (GPs) provide a powerful framework for monitoring and optimization tasks. This study employs two GP-based techniques: co-kriging surrogate modelling and Bayesian optimization. The GP training data comes from the cycling performance test of five CR2032 cells with Ni contents of 0.0, 0.4, 0.5, 0.6, and 1.0 in their cathode active material LiNixMn2−xO4. The co-kriging surrogate predicts the capacity degradation profile of a cell by exploiting information from different cells. Bayesian optimization identifies new Ni compositions that can produce cells with high initial specific capacity and large cycle life. The study shows the predictive capabilities of the co-kriging surrogate when correlated data is available. Bayesian optimization predicts that a Ni content of 0.44 produces cells with an initial specific capacity of 103.4 ± 3.8 mAh g−1 and a cycle life of 595 ± 12 cycles. Furthermore, the Bayesian strategy identifies other Ni contents that can improve the overall quality of the current Pareto front.

A New Biodegradable Stent to Improve the Management of Biliary Strictures in Pediatric Split Liver Transplantation.

Cholestasis due to benign biliary strictures is the most common biliary complication after pediatric split liver transplantation (SLT), decreasing graft survival, but consensus about its management lacks. Percutaneous transhepatic cholangiography, bilioplasty and internal-external biliary drainage (IEBD) are standard treatments. The aim of this report is to present the preliminary experience with a new biodegradable biliary stent in the management of post-SLT biliary strictures. Between September 2020 and April 2021, SLT patients with a single anastomotic benign biliary stricture underwent percutaneous transhepatic implantation of an innovative 10F helical-shaped biodegradable biliary stent, featuring a slow degradation profile, in addition to the standard treatment with bilioplasty and IEBD. The device is unique and the first to be CE-marked for the use in this indication. Six pediatric patients (4 males; median age 8.6years, interquartile range 3.7years)underwent percutaneous stent implantation, without complications nor clinical cholestasis during a median follow-up of 271days (IQR 120.25). Stent dislodgement occurred in one case. Preliminary data suggest that implantation of a new biodegradable biliary stent may be considered in the management of post-SLT cholestasis in pediatric patients. Some technical tips are useful during implantation. This device may prolong biliary drainage, potentially relieving the discomfort of long-term IEBD.

Bilayered laponite/alginate-poly(acrylamide) composite hydrogel for osteochondral injuries enhances macrophage polarization: An in vivo study

Addressing osteochondral defects, the objective of current study was to synthesize bilayered hydrogel, where the cartilage layer was formed by alginate (Alg)-polyacrylamide (PAAm) with and without the addition of TGF-β3 and bone layer by laponite XLS/Alg-PAAm and characterize by in vitro and in vivo experiments. Exceeding the mechanical strength of Alg-PAAm (32.95 ± 1.23 kPa) and XLS based (317.5 ± 21.72 kPa) hydrogels, XLS/Alg-PAAm hydrogel (469.7 ± 6.1 kPa) activated macrophages towards M2 phenotype and stimulated the expression of anti-inflammatory factors. The addition of TGF-β3 accelerated transition of macrophage polarization, especially between day 4 and 7. The expression levels of M1-related genes such as CD80, iNOS and TNF-α decreased gradually after day 4, reaching lowest values at day 13, whereas the expression levels of M2-related genes, CD206, Arg1 and STAT6 significantly increased promoting M2 macrophage polarization, which might be associated with accelerated bone repair. Moreover, bilayer structure exhibited a better cell viability as well as repairment thorough the XLS contents. In vivo histological examinations verified the significant surface regularity and hyaline like tissue formation employment, along with synchronized degradation profile of the hydrogel with tissue healing at the end of 12 weeks. A mechanically durable, biocompatible and immunocompatible hydrogel was formulated to be utilized in bone-cartilage engineering applications.

Stereolithographic Visible-Light Printing of Poly(l-glutamic acid) Hydrogel Scaffolds.

Bioprinting is a promising fabrication technique aimed at developing biologically functional, tissue-like constructs for various biomedical applications. Among the different bioprinting approaches, vat polymerization-based techniques offer the highest feature resolution compared to more commonly used extrusion-based methods and therefore have greater potential to be utilized for printing complex hierarchical tissue architectures. Although significant efforts have been directed toward harnessing digital light processing techniques for high-resolution bioprinting, the use of stereolithography (SLA) setups for producing distinct hydrogel filaments smaller than 20 μm has received less attention. Improving the bioprinting resolution is still a technical challenge that must consider both the practical limitations of the bioprinter apparatus and the formulation of the cytocompatible bioresin. In this study, we developed a novel bioresin compatible with SLA and capable of printing high-resolution features. This resin, composed of a biosynthetic polypeptide poly(l-glutamic acid) functionalized with tyramine moieties (PLGA-Tyr), was crosslinked using a visible-light photoinitiator system. Varying concentrations of PLGA-Tyr and the co-photoinitiator were evaluated for the hydrogel system's gelation ability, swelling characteristics, degradation profiles, mechanical properties, and cell viability post-encapsulation. This study introduces a custom-built, cost-effective, visible-light SLA bioprinting system named the "MicroNC". Using the newly developed visible-light bioresin, we demonstrated for the first time the ability to fabricate hydrogel scaffolds with well-resolved filaments (less than 8 μm in width) capable of supporting cell viability and proliferation and directing cellular morphology at the single-cell level for up to 14 days. Overall, these experiments have underscored the exciting potential of using the visible-light-photoinitiated PLGA-Tyr material system for developing physiologically relevant in vitro hydrogel scaffolds with feature resolutions comparable to the dimensions of individual human cells for a wide range of biomedical applications.

Directed Discovery of Tetrapeptide Emulsifiers

Oil in water emulsions are an important class of soft material that are used in the food, cosmetic, and biomedical industries. These materials are formed through the use of emulsifiers that are able to stabilize oil droplets in water. Historically emulsifiers have been developed from lipids or from large biomolecules such as proteins. However, the ability to use short peptides, which have favorable degradability and toxicity profiles is seen as an attractive alternative. In this work, we demonstrate that it is possible to design emulsifiers from short (tetra) peptides that have tunability (i.e., the surface activity of the emulsion can be tuned according to the peptide primary sequence). This design process is achieved by applying coarse grain molecular dynamics simulation to consecutively reduce the molecular search space from the 83,521 candidates initially considered in the screen to four top ranking candidates that were then studied experimentally. The results of the experimental study correspond well to the predicted results from the computational screening verifying the potential of this screening methodology to be applied to a range of different molecular systems.

Cellulose nanocrystal (CNC)-stabilized Pickering emulsion for improved curcumin storage stability

Curcumin is a bioactive supplement known to have many medical benefits. However, it has low bioavailability due to its insolubility in aqueous solution and rapid degradation profile. In this paper, an oil-in-water (O/W) Pickering emulsion (PE) was fabricated ultrasonically with different cellulose nanocrystal (CNC) concentrations to investigate its effect on the physicochemical properties of PE and the storage stability of curcumin. The CNC-PE produced remained stable for at least one month. The highest encapsulation efficiency of curcumin in CNC-PE was found to exceed 99%. For storage of curcumin containing CNC-PE under dark conditions, good stability of curcumin was observed with a half-life of 98.47 d, reflecting a nearly 20-fold improvement as compared to other existing PE systems. On the other hand, storage under visible light, UV light, and at elevated temperature (50 °C) increased the degradation rate of encapsulated curcumin following the order: 50 °C > UV light > visible light > dark. Our findings elucidated the promising potential of CNC-PE as a food-safe delivery system for sensitive lipophilic bioactive compounds.

Mineral-induced bubbling effect and biomineralization as strategies to create highly porous and bioactive scaffolds for dentin tissue engineering.

The objective of the study was to assess the biological and mechanical characteristics of chitosan-based scaffolds enriched by mineral phases and biomineralized in simulated body fluid (SBF) as a possible biomaterial for dentin regeneration. Thus, porous chitosan scaffolds were prepared by the mineral-induced bubbling-effect technique and subjected to biomineralization to create biomimetic scaffolds for dentin tissue engineering. Suspensions containing calcium hydroxide, nanohydroxyapatite, or β-tricalcium phosphate were added to the chitosan (CH) solution and subjected to gradual freezing and freeze-drying to obtain CHCa, CHnHA, and CHβTCP porous scaffolds, respectively, by the bubbling effect. Then, scaffolds were incubated in SBF for 5 days at 37°C, under constant stirring, to promote calcium-phosphate (CaP) biomineralization. Scanning electron microscopy revealed increased pore size and porosity degree on mineral-containing scaffolds, with CHCa and CHnHA presenting as round, well-distributed, and with an interconnected pore network. Nevertheless, incubation in SBF disrupted the porous architecture, except for CHCaSBF , leading to the deposition of CaP coverage, confirmed by Fourier Transform Infrared Spectroscopy analyses. All mineral-containing and SBF-treated formulations presented controlled degradation profiles and released calcium throughout 28 days. When human dental pulp cells (HDPCs) were seeded onto scaffold structures, the porous and interconnected architecture of CHCa, CHnHA, and CHCaSBF allowed cells to infiltrate and spread throughout the scaffold structure, whereas in other formulations cells were dispersed or agglomerated. It was possible to determine a positive effect on cell proliferation and odontogenic differentiation for mineral-containing formulations, intensely improved by biomineralization. A significant increase in mineralized matrix deposition (by 8.4 to 18.9 times) was observed for CHCaSBF , CHnHASBF , and CHβTCPSBF in comparison with plain CH. The bioactive effect on odontoblastic marker expression (ALP activity and mineralized matrix) was also observed for HDPCs continuously cultivated with conditioned medium obtained from scaffolds. Therefore, biomineralization of chitosan scaffolds containing different mineral phases was responsible for increasing the capacity for mineralized matrix deposition by pulpal cells, with potential for use in dentin tissue engineering.

Evaluation of the Cefalexin Drug Degradation Profile in Pharmaceutical Capsule Forms Based on Forced Degradation Studies

Evaluation of the Cefalexin Drug Degradation Profile in Pharmaceutical Capsule Forms Based on Forced Degradation Studies