Progress in Biomaterials最新文献

Tissue engineering (TE) employs scaffolds as a structural support for initially seeding of cells followed by development of new tissues. Electrospun scaffolds generally function as a template of native extracellular matrix (ECM). The chemical composition of the scaffold and its surface morphology strongly influence the interaction between various cell types and materials. In this work, PCL and PCL/HPMC-based composite membranes with varying concentrations of HPMC (20-30% by weight) were fabricated using electrospinning technique. The membranes were evaluated for their surface, physio-chemical and biological properties. It was observed probably for the first time that blending of HPMC with PCL produced super-hydrophilic scaffolds. DSC studies confirmed the semi- crystalline nature of HPMC. PCL/HPMC composite scaffolds are found biocompatible from cytotoxicity assay. From the cell culture studies (apoptosis), PCL/HPMC composite scaffolds did not inhibit the adhesion of L929 cells due to their super-hydrophilic nature. The cell adhesion and spreading varied with HPMC concentration. PCL/HPMC (70/30) membranes showed highest cell adhesion among others due to its porous structure.

The preparation of hydrogels based on biopolymers like collagen and gum arabic gives a chance to provide novel options that can be used in biomedical field. Through a polymeric semi-interpenetration technique, collagen-based polymeric matrices can be associated with gum arabic while controlling its physicochemical and biological properties. To create novel hydrogels with their potential use in the treatment of wounds, the semi-interpenetration process, altering the concentration (0-40% by wt) of gum arabic in a collagen matrix is explored. The ability of gum arabic to create intermolecular hydrogen bonds in the collagen matrix enables the development of semi-interpenetrating polymeric networks (semi-IPN)-based hydrogels with a faster gelation time and higher crosslinking. Amorphous granular surfaces with linked porosity are present in matrices with 30% (by wt) of gum arabic, enhancing the storage modulus and thermal degradation resistance. The hydrogels swell to very high extent in hydrolytic and proteolytic environments, good hemocompatibility, and suppression of growth of pathogens like E. coli, and all it is enhanced by gum arabic included them, in addition to enabling the controlled release of ketorolac. The chemical composition of theses semi-IPN matrices have no deleterious effects on monocytes or fibroblasts, promoting their proliferation, and lowering alpha tumor necrosis factor (α-TNF) secretion in human monocytes.

Diabetes mellitus is a fast-growing chronic metabolic condition caused by insulin deficiency or resistance, leading to lifelong insulin use. It has become one of the world's most difficult non-communicable diseases. The goal of this study was to view the effectiveness of the combined method of macro- and microencapsulation for islet transplantation. The process of 3D printing is used to make macroencapsulation bags with regulated diffusion properties thanks to the emerging small pored channels. The ink used to manufacture 3D-printed bags with controlled specifications was polyurethane solution (13% w/v). Swelling experiments revealed that there was very little swelling and that the membrane maintained its structural stability. Alginate beads (made from 5% w/v solution) were used to microencapsulate islet cell clusters. Direct contact assay was used to confirm in vitro cytocompatibility. The insulin release from the encapsulated rabbit islets was confirmed using a glucose challenge assay. When challenged with 20 mM glucose on day 7, the encapsulated islet cells released insulin at a rate of 9.72 ± 0.65 mU/L, which was identical to the RIN-5F islet cell line control, confirming the functioning of the encapsulated islets. After 21 days of culture, the islets were shown to be viable utilizing a live-dead assay. As a result, our work demonstrates that 3D printing for macroencapsulating cells, as well as microencapsulation with alginates, is a viable scale-up technology with great potential in the field of pancreatic islet transplantation.

Mucoadhesive polymers improve oral bioavailability of drugs by prolonging the duration of adhesion of drugs with mucosa. Various methods could be employed to address the problems of mucoadhesive polymers like weak adhesion forces. Chemical modification of polymers, such as the addition of a thiol group or thiolation, is another way for improving the polymers' mucoadhesive properties that is studied in present research work. A novel thiomer of chitosan was prepared by attaching 2-mercaptobenzoic acid, a hydrophobic ligand onto it. The docking of thiomer and chitosan with mucin structure showed higher binding energy for former. The prepared thiomer was subjected to X-ray diffraction and DSC which established reduction in crystallinity and formation of a new compound through changes in glass transition, melting point and change in diffraction pattern. The NMR studies established conjugation of 2-mercapto benzoic acid to chitosan. The increased mucoadhesion in thiomer behaviour (2-3 fold) was confirmed through mucus glycoprotein assay as well as through texture analysis. The permeation enhancing the property of thiomer was established by demonstrating the permeation of phenol red across thiomer treated intestinal membrane. An in vitro cell toxicity assay was done to establish toxicity of chitosan and thiolated chitosan. Finally, the reduced water uptake of thiomer over chitosan proved that the increase in mucoadhesion is not contributed by swelling. Thus, a thiomer with improved mucoadhesion and enhanced permeation properties was prepared and characterized. Hence, all these properties render the newly synthesized polymer a better alternative to chitosan as an excipient for mucoadhesive drug delivery systems.

Biphasic calcium phosphate (BCP) bioceramics composed of hydroxyapatite and β-tricalcium phosphate have attracted considerable attention as ideal bone substitutes for reconstructive surgery, orthopedics, and dentistry, owing to their similar chemical composition to bone mineral and biocompatibility. The addition of trace elements to BCP bioceramics, such as magnesium (Mg), cerium (Ce), and silicon (Si), can alter the physicochemical and biological properties of the resulting materials. To improve the anti-inflammatory activity of a pure BCP scaffold, this study developed a simple wet chemical precipitation and gel-casting method to fabricate microporous BCP scaffolds containing Si or Ce. The BCP scaffolds exhibited interconnected microporous structures with uniform micropores and unequiaxed grains. No changes in the phase composition and microstructure of the scaffolds with the Si or Ce doping were observed. Conversely, Si or Ce doping into the BCP crystal lattice influenced the in vitro biological activity of the scaffolds and the bone-forming ability of the cells cultured on the BCP scaffolds. The results of biological activity assays demonstrated that Ce-BCP promoted cell proliferation and osteogenic differentiation more effectively than the other scaffolds. In particular, Ce-BCP significantly suppressed the expression of bone-active cytokines via the anti-inflammatory and anti-oxidative effects. Therefore, Si- or Ce-doped BCP scaffolds can contribute to providing a new generation of bone graft substitutes.

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.