Progress in Biomaterials最新文献

Osteoarthritis (OA) is the most common form of degenerative joint disease, affecting more than 25% of the adults despite its prevalence in the elderly population. Most of the current therapeutic modalities aim at symptomatic treatment which lingers the disease progression. In recent years, regenerative medicine such as stem cell transplantation and tissue engineering has been suggested as a potential curative intervention for OA. The objective of this current study was to assess the safety and efficacy of an injectable tissue-engineered construct composed of rat bone marrow mesenchymal stem cells (rBMMSCs), platelet-rich plasma (PRP), and collagen type I in rat model of OA. To produce collagen type I, PRP and rBMMSCs, male Wistar rats were ethically euthanized. After isolation, culture, expansion and characterization of rBMMSCs, tissue-engineered construct was formed by a combination of appropriate amount of collagen type I, PRP and rBMMSCs. In vitro studies were conducted to evaluate the effect of PRP on chondrogenic differentiation capacity of encapsulated cells. In the following, the tissue-engineered construct was injected in knee joints of rat models of OA (24 rats in 4 groups: OA, OA + MSC, OA + collagen + MSC + PRP, OA + MSC + collagen). After 6 weeks, the animals were euthanized and knee joint histopathology examinations of knee joint samples were performed to evaluate the effect of each treatment on OA. Tissue-engineered construct was successfully manufactured and in vitro assays demonstrated the relevant chondrogenic genes and proteins expression were higher in PRP group than that of others. Histopathological findings of the knee joint samples showed favorable regenerative effect of rBMMSCs + PRP + collagen group compared to others. We introduced an injectable tissue-engineered product composed of rBMMSCs + PRP + collagen with potential regenerative effect on cartilage that has been damaged by OA.

Glycyrrhiza glabra (GG) elicits protective effects against periodontal diseases. However, the sustained bioavailability of GG extract at therapeutic concentration warrants ideal delivery vehicles. Present study has focused on the design, fabrication, and evaluations of ethanolic-crude extract of GG-loaded semi-interpenetrating network (semi-IPN) hydrogel (HAAPS-GG) using alginic acid and polyvinyl alcohol (PVA) hydrogel mosaicked with HA for periodontal regeneration. The study has examined the performance of the hydrogel against the selected oral pathogens S. mutans, E. faecalis, L. acidophilus and C. albicans. HAAPS-GG was successfully fabricated and the surface functional groups were confirmed by attenuated total reflectance-infrared (ATR-IR) spectroscopy. HAAPS-GG displayed interconnecting pores, hydrophilicity and excellent water profile contributing to the biocompatibility as evident from direct contact and MTT assay in L929 fibroblasts. The hydrogel was mechanically stable and was immunocompatible owing to the relatively decreased levels of pro-inflammatory mediators COX2, 5LPO, iNOS and MPO in RAW 264.7 macrophages. In addition, the transcript analysis on RAW 264.7 revealed the down-regulation of inflammatory transcription factor NF-κβ and the pro-inflammatory cytokine TNF-α. Importantly, HAAPS-GG arrested the progression of periodontal pathogens predominantly S. mutans, and C. albicans as evident by disc diffusion assay, MTT assay and confocal microscopy. Overall, the HAAPS-GG system offers promising translational avenues in periodontal regeneration.

We evaluated the influence of the open porosity of alumina (Al₂O₃) substrates on the phase formation of calcium phosphates deposited onto it surface. The Al₂O₃ substrates were prepared with different porosities by the foam-gelcasting method associated with different amounts of polyethylene beads. The substrates were coated biomimetically for 14 and 21 days of incubation in a simulated body fluid (SBF). Scanning electron microscopy characterisation and X-ray computed microtomography showed that the increase in the number of beads provided an increase in the open porosity. The X-ray diffraction and infrared spectroscopy showed that the biomimetic method was able to form different phases of calcium phosphates. It was observed that the increase in the porosity favoured the formation of β-tricalcium phosphate for both incubation periods. The incubation period and the porosity of the substrates can influence the phases and the amount of calcium phosphates formed. Thus, it is possible to target the best application for the biomaterial produced.

Cell therapy is one of the proposed treatments for diabetes. Cell encapsulation and differentiation inside the biodegradable polymers overcome the limitations such as islet deficiency and the host immune responses. This study was set to encapsulate the mesenchymal stem cells (MSCs) and differentiate them into insulin-producing cells (IPCs). Human bone marrow-mesenchymal stem cells (hBM-MSCs) were encapsulated in alginate/trimethyl chitosan/alginate (Alg/TMC/Alg) coating. At first, morphology and swelling properties of the cell-free microcapsules were investigated. Next, a three-step protocol was used in the presence of exendin-4 and nicotinamide to differentiate hBM-MSCs into IPCs. Viability of the encapsulated cells was investigated using MTT assay. The differentiated cells were analyzed using a real-time RT-PCR to investigate Glut-2, Insulin, Pdx-1, Ngn-3, nestin, and Isl-1 gene expression. The results revealed that differentiation of the encapsulated cells was higher than non-encapsulated cells. Also, dithizone staining in  two-dimensional (2D) environment showed the differentiated cell clusters. In summary, here, hBM-MSCs after encapsulation in Alg/TMC/Alg microcapsules, as a new design, were differentiated properly in the presence of exendin-4 and nicotinamide as main inducers. A three-dimensional (3D) matrix is more similar to the native ECM in the body and prepares higher cell-cell contacts.

Curcumin-containing soy protein nanoparticles (curcumin-SPNs) were synthesized by desolvation (coacervation) method and characterized by SEM, DLS, FTIR, and XRD. For anticancer evaluation, osteogenic sarcoma (SAOS2) cell lines were incubated with different concentrations of nanostructures. The dialysis method was used for assessment of drug release. Intracellular reactive oxygen species (ROS) were evaluated in IC50 dose after 24 h of exposure to free curcumin and curcumin-SPNs. Characterization data showed that the size of drug-free SPNs and curcumin-SPNs were 278.2 and 294.7 nm, respectively. The zeta potential of drug-free SPNs and curcumin-SPNs were - 37.1 and - 36.51 mv, respectively. There was no significant difference between the control and drug-free SPNs groups in terms of cell viability (p > 0.05). The viability of cells in different concentrations of the designed curcumin-SPNs in Saos2 cell line was significantly higher than free drug (p < 0.05). The release of curcumin showed that more than 50% of the drug was released in the first 2 h of incubation. After this time, the slow release of drug was continued to 62-83% of drug. IC50 values of free curcumin and curcumin-SPNs (1/10) were 156.8 and 65.9 µg/mL, respectively (a free curcumin IC50 was 2.4 times more than curcumin-SPNs). Slow-release of the curcumin causes the cell to be exposed to the anticancer drug for a longer period of time. The intracellular ROS levels significantly increased in an IC50 dose after 24 h of exposure to both free curcumin and curcumin-SPNs compared with controls (p < 0.05).

Piperic acid, a natural product-based derivative, has been used with polyvinyl alcohol for the first time to form polymer composite films for its suitable modification in physicochemical and antimicrobial properties. Initially, piperic acid was synthesized from piperine, a natural alkaloid extracted from black pepper (Piper nigrum). The solvent casting method was used for the synthesis of PVA-piperic acid composite films. The films were characterized by various spectral and microscopic techniques like UV-visible spectroscopy, FT-IR, SEM, XRD, and TGA. The antibacterial activity was shown by these polymer composites of piperic acid against Gram-positive Staphylococcus aureus (S. aureus-ATCC8738P) and Gram-negative Escherichia coli (E. coli-ATCC8739) was worthwhile. The antifungal activity of the composite films was evaluated by the food poisoning technique. Percentage mycelial growth inhibition was found maximum against Fusarium solani than Aspergillus and Penicillium. The water vapour and oxygen barrier properties are enhanced with the incorporation of increased content of piperic acid. Also, enhancement in the tensile strength of PVA/PA composite film was observed, while elongation at break shows decreased trend with the addition of piperic acid. The surface properties of polymer composite films were determined by contact angle measurements. Contact angle shows a considerable increase in these films when compared to virgin PVA film. It was increased by 56.1° in 15 mL composite film containing a higher concentration of piperic acid than virgin PVA.

Regeneration solutions for the osteochondral interface depth are limited, where multi-material implants have the potential to delaminate affecting the regeneration process and impacting the final integrity of tissue interface. Here we explore regionally mixed hydrogel networks, presenting distinct chemical features to determine their compatibility in supporting osteogenic or chondrogenic cell behaviour and differentiation. Poly(N-isopropylacrylamide) (pNIPAM) and poly(N-tert-butylacrylamide) (pNTBAM) hydrogels were assessed in terms of their chemical differences, mechanical strength, internal architecture, porosity and capacity to support cell viability, migration, and differentiation. pNTBAM polymerized with a Young's modulus of up to 371 ± 31 kPa compared to the more flexible pNIPAM, 16.5 ± 0.6 kPa. Viability testing revealed biocompatibility of both hydrogels with significantly increased cell numbers observed in pNTBAM (500 ± 95 viable cells/mm²) than in pNIPAM (60 ± 3 viable cells/mm²) (P ≤ 0.05). Mineralization determined through alkaline phosphatase (ALP) activity, calcium ion and annexin A2 markers of mineralization) and osteogenic behaviour (collagen I expression) were supported in both hydrogels, but to a greater extent in pNTBAM. pNTBAM supported significantly elevated levels of chondrogenic markers as evidenced by collagen II and glycosaminoglycan expression in comparison to little or no evidence in pNIPAM (P ≤ 0.05). In conclusion, structurally similar, chemically distinct, acrylamide hydrogels display variable capacities in supporting osteochondral cell behaviours. These systems demonstrate spatial control of cell interaction through simple changes in monomer chemistry. Fine control over chemical presentation during the fabrication of biomaterial implants could lead to greater efficacy and targeted regeneration of semi-complex tissues.

This work uses optimization study to formulate a patient-friendly antitussive fast-dissolving oral film based on phenylephrine hydrochloride (Phen) and dextromethorphan hydrobromide (Dex). The designed films were based on hydroxypropylmethyl cellulose (HPMC) with two grades (E5 and E50) as a film-forming polymer by the solvent-casting method. Polyethylene glycol with two molar masses (400 and 1000) was used as a plasticizer, while aspartame was used as a sweetener and microcrystalline cellulose intended to act as a disintegrant. To find an optimum formulation, a response surface methodology and a central composite design were employed. The percentage of HPMC E50, and PEG, as a plasticizer, were considered to be the design factors. Film thickness, surface pH, disintegration time, dissolution percent, tensile strength, elongation percent and folding endurance were considered to be the responses. A film with 11.46% E50, 88.54% E5, 25% of two drugs (8.4% of Phen and 16.6% of Dex) and 18.54% plasticizer is designed and prepared as the optimum formulation for Phen/Dex fast-dissolving oral films, with 95% confidence levels.

Currently, the treatment of burns poses a significant challenge to clinical surgical. The use of nanofibers combined with drugs provides an entirely new option for treating burns. Alum-borneol combination has been shown as a promising alternative in clinical burn treatment. However, the utilization of the alum-borneol combination is not optimistic due to the low solubility of borneol. In this study, alum-borneol incorporated polyvinyl pyrrolidone fibers with a core-shell structure were fabricated through coaxial electrospinning. In vitro Borneol release behavior of fibers with different ratios of alum to borneol was explored. Scanning electron microscopy, transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimeter, in vitro drug release, and in vitro release mechanism were evaluated. The results showed that the fiber membranes maintained an integrated morphology. In vitro dissolution data showed an improved solubility of borneol, which reached more than 82% at 240 min in alum-borneol fibers. It was 4.8 times higher than borneol powder, and the ratio of alum to borneol was 2:1 for the best results. Therefore, alum-borneol incorporated polyvinyl pyrrolidone fibers can significantly improve the dissolution rate of borneol, which opens up a new way for the combined application of the alum and borneol.

Despite the importance of the proper quality of blood products for safe transfusion, conventional methods for preparation and their preservation, they lack significant stability. Non-metal nanoparticles with particular features may overcome these challenges. This review study for the first time provided a comprehensive vision of the interaction of non-metal nanoparticles with each blood product (red blood cells, platelets and plasma proteins). The findings of this review on the most effective nanoparticle for improving the stability of RBCs indicate that graphene quantum dots and nanodiamonds show compatibility with RBCs. For increasing the stability of platelet products, silica nanoparticles exhibited a suppressive impact on platelet aggregation. Pristine graphene also shows compatibility with platelets. For better stability of plasma products, graphene oxide was indicated to preserve free human serum albumin from thermal shocks at low ionic strength. For increased stability of Factor VIII, mesoporous silica nanoparticles with large pores exhibit the superb quality of recovered proteins. Furthermore, 3.2 nm quantum dots exhibited anticoagulant effects. As the best promising nanoparticles for immunoglobulin stability, graphene quantum dots showed compatibility with γ-globulins. Overall, this review recommends further research on the mentioned nanoparticles as the most potential candidates for enhancing the stability and storage of blood components.