Progress in Biomaterials

Acceleration in healing of infected full-thickness wound with novel antibacterial γ-AlOOH-based nanocomposites
Parastar H, Farahpour MR, Shokri R, Jafarirad S and Kalantari M
This study was conducted to synthesize γ-AlOOH (bohemite)-based nanocomposites (NCs) of Au/γ-AlOOH-NC and its functionalized derivative using chitosan (Au/γ-AlOOH/Ctn-NC) and with the help of one-step Mentha piperita. The physicochemical characteristics of the NCs were investigated. In addition, biomedical properties, such as antibacterial activity under in vitro and in vivo conditions, and cell viability were assessed. Wound healing activity on infected wounds and histological parameters were assessed. The gene expressions of TNF-α, Capase 3, Bcl-2, Cyclin-D1 and FGF-2 were investigated. The TEM and FESEM images showed the sheet-like structure for bohemite in Au/γ-AlOOH-NC with Au nanoparticles in a range of 14-15 nm. The elemental analysis revealed the presence of carbon, oxygen, aluminum, and Au elements in the as-synthesized Au/γ-AlOOH. The results for toxicity showed that the produced nanocomposites did not show any cytotoxicity. Biomedical studies confirmed that Au/γ-AlOOH-NC and Au/γ-AlOOH/Ctn-NC have anti-bacterial properties and could expedite the wound healing process in infected wounds by an increase in collagen biosynthesis. The administration of ointment containing Au/γ-AlOOH-NC and Au/γ-AlOOH/Ctn-NC decreased the expressions of TNF-α, and increased the expressions of Capase 3, Bcl-2, Cyclin-D1 and FGF-2. The novelty of this study was that bohemite and Au nanoparticles can be used as a dressing to accelerate the wound healing process. In green synthesis of Au/γ-AlOOH-NC, phytochemical compounds of the plant extract are appropriate reagents for stabilization and the production of Au/γ-AlOOH-NC. Therefore, the new bohemite-based NCs can be considered as candidate for treatment of infected wounds after future clinical studies.
Correction to: Sustained release of valproic acid loaded on chitosan nanoparticles within hybrid of alginate/chitosan hydrogel with/without stem cells in regeneration of spinal cord injury
Jafarimanesh MA, Ai J, Shojaei S, Khonakdar HA, Darbemamieh G and Shirian S
Mechanical performance and bioactivation of 3D-printed PEEK for high-performance implant manufacture: a review
Rendas P, Figueiredo L, Machado C, Mourão A, Vidal C and Soares B
Polyetheretherketone (PEEK) has stood out as the leading high-performance thermoplastic for the replacement of metals in orthopaedic, trauma and spinal implant applications due to its high biocompatibility and mechanical properties. Despite its potential for custom-made medical devices, 3D-printed PEEK's mechanical performance depends on processing parameters and its bioinertness may hinder bone opposition to the implant. Concerning these challenges, this review focuses on the available literature addressing the improvement of the mechanical performance of PEEK processed through "fused filament fabrication" (FFF) along with literature on bioactivation of PEEK for improved osseointegration. The reviewed research suggests that improvements can be achieved in mechanical performance of 3D-printed PEEK with adequate FFF parametrization while different bioactivation techniques can be used to improve the bioperformance of 3D-printed PEEK. The adequate approaches towards these procedures can increase PEEK's potential for the manufacture of high-performance custom-made implantable devices that display improved bone-implant integration and prevent stress shielding of the treated bone.
PCL-based 3D nanofibrous structure with well-designed morphology and enhanced specific surface area for tissue engineering application
Hejazi F, Mirzadeh H and Shojaei S
Tissue engineering opens a new horizon for biological tissue replacement applications. Scaffolds, appropriate cells, and signaling induction are the main three determinant parameters in any tissue engineering applications. Designing a suitable scaffold which can mimic the cellular inherent and natural habitation is of great importance for cellular growth and proliferation. Just like a natural extracellular matrix (ECM), scaffolds provide the cells with an environment for performing biological functions. Accordingly, vast surface area and three-dimensional nanofibrous structures are among the pivotal characteristics of functional scaffolds in tissue engineering, and enhancement of their properties is the main purpose of the present research. In our previous study, a patterned structure composed of continuous nanofibers and microparticles was introduced. In this work, a new modification is applied for adjustment of the surface area of an electrospun/electrosprayed scaffold. For this purpose, at predetermined stages during electrospinning/electrospraying, the nitrogen gas is flushed through the mesh holes of the collector in the opposite direction of the jet movement. This method has led to the formation of very thin nanofibrous layers at nitrogen flush intervals by providing a cooling effect of the sweeping nitrogen. As a consequence, a straticulated structure has been fabricated which possesses extremely high surface/volume ratio. The porosity, water absorption, and morphological analysis were conducted on the obtained scaffold. In vitro cytocompatibility assessments as well as histological analysis demonstrated that the fabricated scaffold provides a proper substrate for cellular attachment, proliferation and infiltration. These findings can be advantageous in three-dimensional tissue engineering such as bone tissue engineering applications. Furthermore, according to the advanced microstructure and vast surface area of the fabricated samples, they can be applied in many other applications, such as membrane, filtration, etc.
Sustained release of valproic acid loaded on chitosan nanoparticles within hybrid of alginate/chitosan hydrogel with/without stem cells in regeneration of spinal cord injury
Jafarimanesh MA, Ai J, Shojaei S, Khonakdar HA, Darbemamieh G and Shirian S
Hydrogels have been increasingly applied in tissue regeneration and drug delivery systems (DDS). In this study, the capacity of valproic acid (Val) encapsulated within hybrid of alginate (Alg)-chitosan (Cs) (Alg-Cs) hydrogel containing Cs nanoparticle (Npch) with/without human endometrial stem cells (hEnSC) was initially examined for regeneration of spinal cord injury (SCI). To evaluate the stability of the synthesized hydrogels zeta potential necessary measurements were made. Physicochemically, the developed hydrogels were evaluated using Fourier-transform infrared (FTIR) spectroscopy. The physical properties including degradation rate, swelling ability, and tunability of the synthesized hydrogels were studied. To evaluate the nerve regeneration ability of the synthesized hydrogels, 35 Sprague-Dawley rats were undergone SCI. The spinal cords were exposed using laminectomy in T9-T10 area and the hemi-section SCI model was made. The rats were then randomly divided into 5 groups (n = 7) including, Alg-Cs/Npch, Alg-Cs/Npch/hEnSCs, Alg-Cs/Npch/Val, and Alg-Cs/Npch/hEnScs/Val, and the control groups without any intervention. The FTIR spectra showed band frequencies and assignments of Val, Alg-Cs, and alginate. Nanoparticles were formulated with a mean diameter of 187 and 210 nm, for Val/Alg-Cs and Alg-Cs, respectively. The loading of Val into Alg-Cs led to its reduced size by about 40 nm. The Cs-Npch/Val hydrogels degraded faster than the Alg-Cs-/Npch/Val hydrogel specifically in extended time of incubation. A higher swelling capacity of Alg-Cs/Npch hydrogel, compared to Cs/Npch/Val and Alg-Cs/Npch/Val hydrogels, was found. The Cs-Npch/Val hydrogels degraded faster than Alg-Cs-/Npch/Val hydrogel. The Alg-Cs/Npch/hEnSCs/Val could regenerate the damaged nerve fibers and histologically prevent the SCI-induced vacuolization spaces. The prepared Alg-Cs/Npch/Val could be a suitable polymeric carrier for taurine drugs as bioactive substrate in nerve tissue engineering (NTE) and DDS.
Chitosan scaffolds with mesoporous hydroxyapatite and mesoporous bioactive glass
Pádua AS, Figueiredo L, Silva JC and Borges JP
Bone regeneration is one of the most well-known fields in tissue regeneration. The major focus concerns polymeric/ceramic composite scaffolds. In this work, several composite scaffolds based on chitosan (CH), with low and high molecular weights, and different concentrations of ceramics like mesoporous bioactive glass (MBG), mesoporous hydroxyapatite (MHAp) and both MBG and MHAp (MC) were produced by lyophilization. The purpose is to identify the best combination regarding optimal morphology and properties. The tests of the scaffolds present a highly porous structure with interconnected pores. The compression modulus increases with ceramic concentration in the scaffolds. Furthermore, the 75%MBG (835 ± 160 kPa) and 50%MC (1070 ± 205 kPa) samples are the ones that mostly enhance increases in mechanical properties. The swelling capacity increases with MBG and MC, respectively, to 700% and 900% and decreases to 400% when MHAp concentration increases. All scaffolds are non-cytotoxic at 12.5 mg/mL. The CHL scaffolds improve cell adhesion and proliferation compared to CHH, and the MC scaffold samples, show better results than those produced with just MBG or MHAp. The composite scaffolds of chitosan with MBG and MHAp, have revealed to be the best combination due to their enhanced performance in bone tissue engineering.
Anticancer potential of biologically synthesized silver nanoparticles using Lantana camara leaf extract
Hublikar LV, Ganachari SV, Patil VB, Nandi S and Honnad A
A Lantana camara leaf (LC) extract was used as a mild reducing agent to produce silver metal nanoparticles (LC-AgNPs) efficiently. The size, shape, and morphology of synthesized silver nanoparticles were verified. LC-AgNPs were found in LC extract by XRD. The optimal concentrations of silver nitrate and LC extract necessary for the production of stable silver nanoparticles were determined. The LC-AgNPs were found spherical in form and monodispersed. Under optimal conditions, the round LC-AgNPs of 50-90 nm were utilized to cure lung cancer (A549 cell line) and breast cancer (MCF7) cell lines. Finally, the produced LC-AgNPs enhanced anti-cancer efficacy against A549 cells, with an IC50 = 49.52 g/mL. Similarly, the effect of LC-AgNPs on MCF7 cell line was assessed using an MTT test and inhibitory concentration (IC50) was determined found that 46.67 g/mL.
3D-printed polyurethane immunoisolation bags with controlled pore architecture for macroencapsulation of islet clusters encapsulated in alginate gel
Joy T and Thomas LV
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.
Albumin-loaded thermo/pH dual-responsive nanogels based on sodium alginate and poly (N-vinyl caprolactam)
Mohammad Gholiha H, Ehsani M, Saeidi A and Ghadami A
During the past decades, many researchers have tried to encapsulate medicines in biopolymer nanogels as injectable medicines. In the present study, dual-responsive bovine serum albumin (BSA)-loaded nanogels prepared from sodium alginate grafted poly (N-vinyl caprolactam) (PNVCL) have been reported. First, PNVCL-g-sodium alginate (PNVCL-g-Alg) was synthesized through free radical polymerization, and then nanogels were obtained from ionic crosslinking of sodium alginate in the presence of BSA. FTIR spectra showed that PNVCL-g-Alg nanogels were successfully prepared. Turbidimetry and rheometry analyses demonstrated the cloud point temperature near the human body. Particle size was evaluated using FE-SEM and dynamic light scattering and it was found that the size of particles in dry and swollen state are about 30 and 280 nm, respectively. The effect of temperature and pH on BSA release was evaluated. By comparing the drug release behavior, we found that the release of the protein at the temperature above the cloud point is faster than that at the temperature below the cloud point. The pH sensitivity of BSA-loaded PNVCL-g-Alg was evaluated at pH 5.5 and 7.4 and showed that the drug release was faster at acidic pH than at neutral pH.
Knot strength and antimicrobial evaluations of partially absorbable suture
Odili CC, Ilomuanya MO, Sekunowo OI, Gbenebor OP and Adeosun SO
Partially absorbable suture is useful for orthopedic repair as it possesses the capacity to promote a balance between strength, degradation rate and minimal inflammation. Still, the availability of partially absorbable suture is scarce. So far, no study has examined the mechanical strength and anti-microbial properties of partially absorbable monofilament suture made of low-density polyethylene (LDPE)/polylactide (PLA)/chitosan (CHS); hence, the reason for this study with a view to improve knot strength, antimicrobial property and degradation rate. In this study, monofilament suture was extruded using different weight fractions of LDPE, PLA and CHS. In vitro degradation studies were carried out using phosphate buffer solution (PBS). Mechanical and morphological changes were also examined. A standard Fourier transform infrared spectral of 3433, 2909-2840, 1738, 1452, 1174, 1062, 706 cm were assigned to OH group, C-H stretch, C=O vibration of ester, CH bending, alkyl ester and CH stretch, respectively. Tensile strength of knotted neat LDPE (4.84 MPa) exhibited 48.7% improvement in LDPE/PLA/CHS (60/39.5/0.5). This suggests that a good knot can be achieved to 40% weight fraction of PLA. The monofilament suture also demonstrated better antimicrobial property as the monofilament, LDPE/PLA/CHS (60/39.5/0.5) and LDPE/PLA/CHS (50/49.5/0.5) covered 12.7 mm zone of inhibition which is greater than the standard 1 mm. The suture's morphological phases show dark fibre-like rough surfaces with microstructural irregularities as PLA and CHS were added to the matrix, which is required for enhanced degradation. Thus, the partially absorbable suture produced in this study could serve as a suture for tendon repair.
Delivery of bone morphogenetic protein-2 by crosslinking heparin to nile tilapia skin collagen for promotion of rat calvaria bone defect repair
Ma L, Fu L, Gu C, Wang H, Yu Z, Gao X, Zhao D, Ge B and Zhang N
Collagen has been widely used as a biomaterial for tissue regeneration. At the present, aqua-collagen derived from fish is poorly explored for biomedical material applications due to its insufficient thermal stability. To improve the bone repair ability and thermal stability of fish collagen, the tilapia skin collagen was crosslinked by EDC/NHS with heparin to bind specifically to BMP-2. The thermal stability of tilapia skin collagen crosslinked with heparin (HC-COL) was detected by differential scanning calorimetry (DSC). Cytotoxicity of HC-COL was assessed by detecting MC3T3-E1 cell proliferation using CCK-8 assay. The specific binding of BMP-2 to HC-COL was tested and the bioactivity of BMP-2-loaded HC-COL (HC-COL-BMP-2) was evaluated in vitro by inducing MC3T3-E1 cell differentiation. In vivo, the bone repair ability of HC-COL-2 was evaluated using micro-CT and histological observation. After crosslinking by EDC/NHS, the heparin-linked and the thermostability of the collagen of Nile Tilapia were improved simultaneously. HC-COL has no cytotoxicity. In addition, the binding of BMP-2 to HC-COL was significantly increased. Furthermore, the in vitro study revealed the effective bioactivity of BMP-2 binding on HC-COL by inducing MC3T3-E1 cells with higher ALP activity and the formation of mineralized nodules. In vivo studies showed that more mineralized and mature bone formation was achieved in HC-COL-BMP-2 group. The prepared HC-COL was an effective BMP-2 binding carrier with enough thermal stability and could be a useful biomaterial for bone repair.
Fabrication and characterization of super-hydrophilic poly (ε-caprolactone)/hydroxypropyl methylcellulose (HPMC) based composite electrospun membranes for tissue engineering applications
Sowmya B and Panda PK
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.
Semi-IPN hydrogels of collagen and gum arabic with antibacterial capacity and controlled release of drugs for potential application in wound healing
Amaya-Chantaca NJ, Caldera-Villalobos M, Claudio-Rizo JA, Flores-Guía TE, Becerra-Rodríguez JJ, Soriano-Corral F and Herrera-Guerrero A
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.
Antimicrobial effects of hydroxyapatite mosaicked polyvinyl alcohol-alginate semi-interpenetrating hydrogel-loaded with ethanolic extract of Glycyrrhiza glabra against oral pathogens
Chenicheri S, Ramachandran R and Rajamanikam U
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.
Antimicrobial cryogel dressings towards effective wound healing
Akin B and Ozmen MM
Cryogels are macroporous hydrogels that have been widely utilized in a variety of biomedical applications including wound dressings. Cryogels reveal superior mechanical and swelling properties as well as large and interconnected porosity. As traditional hydrogel wound dressings generally show undesirable mechanical and swelling characteristics, cryogels, due to their toughness and superfast swelling, offer an outstanding platform to address the growing number of various types of wounds. Moreover, recently, cryogel wound dressings loaded with an antimicrobial agent emerged as a feasible option to reduce infection, and thus improve the wound healing process. However, a comprehensive review of antimicrobial cryogels as a wound dressing is still lacking in the literature. In this review, we summarize the progress of cryogels in the area of wound dressings and provide an overview of the various polymers, namely, natural and synthetic which have been employed in cryogel wound dressing preparation. Furthermore, the most prominent antimicrobial agents incorporated in cryogel wound dressings are provided. Finally, the future directions of cryogel wound dressings for wound healing are also discussed.
Analysis of decellularized mouse liver fragment and its recellularization with human endometrial mesenchymal cells as a candidate for clinical usage
Panahi F, Baheiraei N, Sistani MN and Salehnia M
Decellularized tissue has been used as a natural extracellular matrix (ECM) or bioactive biomaterial for tissue engineering. The present study aims to compare and analyze different decellularization protocols for mouse liver fragments and cell seeding and attachment in the created scaffold using human endometrial mesenchymal cells (hEMCs).After collecting and dissecting the mouse liver into small fragments, they were decellularized by Triton X-100 and six concentrations of sodium dodecyl sulfate (SDS; 0.025, 0.05, 0.1, 0.25, 0.5, and 1%) at different exposure times. The morphology and DNA content of decellularized tissues were studied, and the group with better morphology and lower DNA content was selected for additional assessments. Masson's tri-chrome and periodic acid Schiff staining were performed to evaluate ECM materials. Raman confocal spectroscopy analysis was used to quantify the amount of collagen type I, III and IV, glycosaminoglycans and elastin. Scanning electron microscopy and MTT assay were applied to assess the ultrastructure and porosity and cytotoxicity of decellularized scaffolds, respectively. In the final step, hEMCs were seeded on the decellularized scaffold and cultured for one week, and finally the cell attachment and homing were studied morphologically.The treated group with 0.1% SDS for 24 h showed a well preserved ECM morphology similar to native control and showing the minimum level of DNA. Raman spectroscopy results demonstrated that the amount of collagen type I and IV was not significantly changed in this group compared to the control, but a significant reduction in collagen III and elastin protein levels was seen (P < 0.001). The micrographs showed a porous ECM in decellularized sample similar to the native control with the range of 2.25 µm to 7.86 µm. After cell seeding, the infiltration and migration of cells in different areas of the scaffold were seen. In conclusion, this combined protocol for mouse liver decellularization is effective and its recellularization with hEMCs could be suitable for clinical applications in the future.
Synthesis, physical properties, and biomedical applications of magnetic nanoparticles: a review
Keshri S and Biswas S
Recent innovations in nanotechnology have opened the applicability of multifunctional nanoparticles (NPs) in biomedical diagnosis and treatment. The examples of NPs which have attracted considerable attention in recent years are metals (e.g., Au, Ag, Mg), alloys (e.g., Fe-Co, Fe-Pd, Fe-Pt, Co-Pt), iron oxides (e.g., FeO and FeO), substituted ferrites (e.g., MnFeO and CoFeO), manganites (e.g., [Formula: see text]), etc. Special attention has been paid to magnetic NPs (MNPs), as they are the potential candidates for several biomedical appliances, such as hyperthermia applications, magnetic resonance imaging, contrast imaging, and drug delivery. To achieve effective MNPs, a thorough investigation on the synthesis, and characteristic properties, including size, magnetic properties, and toxicity, is required. Furthermore, the surfaces of the NPs must be tailored to improve the biocompatibility properties and reduce agglomeration. The present review focuses on different mechanisms to develop biocompatible MNPs. The utility of these MNPs in various biomedical applications, especially in treating and diagnosing human diseases, such as targeted drug delivery, hyperthermia treatment for cancer, and other biomedical diagnoses, is thoroughly discussed in this article. Different synthetic processes and important physical properties of these MNPs and their biocomposites are presented.
Tailoring the properties of chitosan by grafting with 2-mercaptobenzoic acid to improve mucoadhesion: in silico studies, synthesis and characterization
Marwaha TK, Madgulkar A, Bhalekar M, Asgaonkar K, Gachche R and Shewale P
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.
Effect of silicon or cerium doping on the anti-inflammatory activity of biphasic calcium phosphate scaffolds for bone regeneration
Kim HW and Kim YJ
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.
Nigella/honey/garlic/olive oil co-loaded PVA electrospun nanofibers for potential biomedical applications
Uddin MN, Mohebbullah M, Islam SM, Uddin MA and Jobaer M
The current work focuses on the formation of nanofibrous mats without the use of toxic solvents and metallic nanoparticles utilizing polyvinyl alcohol (PVA) and a blend of nigella, honey, garlic, and olive oil. Using deionized water (DI) water as a solvent, nanofibrous mats composed of PVA/nigella/honey (PNH) and PVA/garlic/honey/olive oil (PGHO) were developed. Methanol extraction was utilized to extract the therapeutic components of nigella sativa. Antibacterial and moisture management tests (MMT) were employed to examine the antibacterial and absorbance characteristics of the PNH and PGHO nanofibrous. Scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR) tests were employed to analyze the morphological and chemical characteristics. PGHO showed thermal stability up to 245 °C, and PNH withstands until 225 °C. PNH and PGHO both exhibited antibacterial activity against Staphylococcus aureus (S. aureus), with inhibition zones of 36 mm and 35 mm, respectively. The synthesized materials exhibited excellent absorbance properties, thermal stability, cytotoxicity, and the production of thin nanofibers with an average diameter between 150 and 170 nm. The samples were characterized using FTIR spectra, which confirmed the presence of all components in the developed samples. To date, extensive research on electrospinning for biomedical applications has been undertaken using a variety of hazardous solvents and metallic nanoparticles. Briefly, our objective is to develop nanofibrous materials from plant extracts through a process called "green electrospinning" to observe the synergistic effect of multiple biocomponents incorporated nanofibers avoiding toxic solvents and metallic compounds for potential biomedical applications.
Encapsulation of rat bone marrow-derived mesenchymal stem cells (rBMMSCs) in collagen type I containing platelet-rich plasma for osteoarthritis treatment in rat model
Islam MS, Ebrahimi-Barough S, Al Mahtab M, Shirian S, Aghayan HR, Arjmand B, Allahverdi A, Ranjbar FE, Sadeg AB and Ai J
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.