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  1. Shafiei M, Ansari MNM, Razak SIA, Khan MUA
    Polymers (Basel), 2021 Jul 30;13(15).
    PMID: 34372132 DOI: 10.3390/polym13152529
    Tissue engineering and regenerative medicine are generally concerned with reconstructing cells, tissues, or organs to restore typical biological characteristics. Liposomes are round vesicles with a hydrophilic center and bilayers of amphiphiles which are the most influential family of nanomedicine. Liposomes have extensive research, engineering, and medicine uses, particularly in a drug delivery system, genes, and vaccines for treatments. Exosomes are extracellular vesicles (EVs) that carry various biomolecular cargos such as miRNA, mRNA, DNA, and proteins. As exosomal cargo changes with adjustments in parent cells and position, research of exosomal cargo constituents provides a rare chance for sicknesses prognosis and care. Exosomes have a more substantial degree of bioactivity and immunogenicity than liposomes as they are distinctly chiefly formed by cells, which improves their steadiness in the bloodstream, and enhances their absorption potential and medicinal effectiveness in vitro and in vivo. In this review, the crucial challenges of exosome and liposome science and their functions in disease improvement and therapeutic applications in tissue engineering and regenerative medicine strategies are prominently highlighted.
  2. Khan MUA, Haider S, Shah SA, Razak SIA, Hassan SA, Kadir MRA, et al.
    Int J Biol Macromol, 2020 May 15;151:584-594.
    PMID: 32081758 DOI: 10.1016/j.ijbiomac.2020.02.142
    Arabinoxylan (AX) is a natural biological macromolecule with several potential biomedical applications. In this research, AX, nano-hydroxyapatite (n-HAp) and titanium dioxide (TiO2) based polymeric nanocomposite scaffolds were fabricated by the freeze-drying method. The physicochemical characterizations of these polymeric nanocomposite scaffolds were performed for surface morphology, porosity, swelling, biodegradability, mechanical, and biological properties. The scaffolds exhibited good porosity and rough surface morphology, which were efficiently controlled by TiO2 concentrations. MC3T3-E1 cells were employed to conduct the biocompatibility of these scaffolds. Scaffolds showed unique biocompatibility in vitro and was favorable for cell attachment and growth. PNS3 proved more biocompatible, showed interconnected porosity and substantial mechanical strength compared to PNS1, PNS2 and PNS4. Furthermore, it has also showed more affinity to cells and cell growth. The results illustrated that the bioactive nanocomposite scaffold has the potential to find applications in the tissue engineering field.
  3. Khan MUA, Razak SIA, Rehman S, Hasan A, Qureshi S, Stojanović GM
    Int J Biol Macromol, 2022 Dec 01;222(Pt A):462-472.
    PMID: 36155784 DOI: 10.1016/j.ijbiomac.2022.09.153
    Globally, people suffering from bone disorders are steadily increasing and bone tissue engineering is an advanced approach to treating fractured and defected bone tissues. In this study, we have prepared polymeric nanocomposite by free-radical polymerization from sodium alginate, hydroxyapatite, and silica with different GO amounts. The porous scaffolds were fabricated using the freeze drying technique. The structural, morphological, mechanical, and wetting investigation was conducted by Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscope, universal tensile machine, and water contact angle characterization techniques. The swelling, biodegradation, and water retention were also studied. The biological studies were performed (cell viability, cell adherence, proliferation, and mineralization) against osteoblast cell lines. Scaffolds have exhibited different pore morphology SAG-1 (pore size = 414.61 ± 56 μm and porosity = 81.45 ± 2.17 %) and SAG-4 (pore size = 195.97 ± 82 μm and porosity = 53.82 ± 2.45 %). They have different mechanical behavior as SAG-1 has the least compression strength and compression modulus 2.14 ± 2.35 and 16.51 ± 1.27 MPa. However, SAG-4 has maximum compression strength and compression modulus 13.67 ± 2.63 and 96.16 ± 1.97 MPa with wetting behavior 80.70° and 58.70°, respectively. Similarly, SAG-1 exhibited the least and SAG-4 presented maximum apatite mineral formation, cell adherence, cell viability, and cell proliferation against mouse pre-osteoblast cell lines. The increased GO amount provides different multifunctional materials with different characteristics. Hence, the fabricated scaffolds could be potential scaffold materials to treat and regenerate fracture bone tissues in bone tissue engineering.
  4. Khan MUA, Razaq SIA, Mehboob H, Rehman S, Al-Arjan WS, Amin R
    Polymers (Basel), 2021 Oct 27;13(21).
    PMID: 34771258 DOI: 10.3390/polym13213703
    The treatment of successive skin wounds necessitates meticulous medical procedures. In the care and treatment of skin wounds, hydrogels produced from natural polymers with controlled drug release play a crucial role. Arabinoxylan is a well-known and widely available biological macromolecule. We produced various formulations of blended composite hydrogels (BCHs) from arabinoxylan (ARX), carrageenan (CG), and reduced graphene oxide (rGO) using and cross-linked them with an optimal amount of tetraethyl orthosilicate (TEOS). The structural, morphological, and mechanical behavior of the BCHs samples were determined using Fourier-transform infrared spectroscopy (FT-IR), Scanning electron microscope (SEM), mechanical testing, and wetting, respectively. The swelling and degradation assays were performed in phosphate-buffered saline (PBS) solution and aqueous media. Maximum swelling was observed at pH 7 and the least swelling in basic pH regions. All composite hydrogels were found to be hemocompatible. In vitro, silver sulfadiazine release profile in PBS solution was analyzed via the Franz diffusion method, and maximum drug release (87.9%) was observed in 48 h. The drug release kinetics was studied against different mathematical models (zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas, and Baker-Lonsdale models) and compared their regression coefficient (R2) values. It was observed that drug release follows the Baker-Lonsdale model, as it has the highest value (0.989) of R2. Hence, the obtained results indicated that, due to optimized swelling, wetting, and degradation, the blended composite hydrogel BCH-3 could be an essential wound dressing biomaterial for sustained drug release for skin wound care and treatment.
  5. Khan MUA, Razak SIA, Ansari MNM, Zulkifli RM, Ahmad Zawawi N, Arshad M
    Polymers (Basel), 2021 Oct 20;13(21).
    PMID: 34771168 DOI: 10.3390/polym13213611
    Several significant advancements in the field of bone regenerative medicine have been made in recent years. However, therapeutic options, such as bone grafts, have several drawbacks. There is a need to develop an adequate bone substitute. As a result, significant bone defects/injuries pose a severe challenge for orthopaedic and reconstructive bone tissue. We synthesized polymeric composite material from arabinoxylan (ARX), β-glucan (BG), nano-hydroxyapatite (nHAp), graphene oxide (GO), acrylic acid (AAc) through free radical polymerization and porous scaffold fabricated using the freeze-drying technique. These fabricated porous scaffolds were then coated with chitosan solution to enhance their biological activities. The complex structure of BG, nHAp, GO was studied through various characterization and biological assays. The structural, morphological, wetting and mechanical analyses were determined using FT-IR, XRD, XPS, SEM/EXD, water contact angle and UTM. The swelling (aqueous and PBS media) and degradation (PBS media) observed their behavior in contact with body fluid. The biological activities were conducted against mouse pre-osteoblast cell lines. The result found that BGH3 has desirable morphological, structural with optimum swelling, degradation, and mechanical behavior. It was also found to be cytocompatible against MC3T3-E1 cell lines. The obtained results confirmed that the fabricated polymeric scaffolds would be a potential bone substitute to regenerate defective bone with different loading bearing applications for bone tissue engineering.
  6. Khan MUA, Stojanović GM, Rehman RA, Moradi AR, Rizwan M, Ashammakhi N, et al.
    ACS Omega, 2023 Oct 31;8(43):40024-40035.
    PMID: 37929099 DOI: 10.1021/acsomega.2c06825
    Biopolymer-based bioactive hydrogels are excellent wound dressing materials for wound healing applications. They have excellent properties, including hydrophilicity, tunable mechanical and morphological properties, controllable functionality, biodegradability, and desirable biocompatibility. The bioactive hydrogels were fabricated from bacterial cellulose (BC), gelatin, and graphene oxide (GO). The GO-functionalized-BC (GO-f-BC) was synthesized by a hydrothermal method and chemically crosslinked with bacterial cellulose and gelatin using tetraethyl orthosilicate (TEOS) as a crosslinker. The structural, morphological, and wettability properties were studied using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a universal testing machine (UTM), respectively. The swelling analysis was conducted in different media, and aqueous medium exhibited maximum hydrogel swelling compared to other media. The Franz diffusion method was used to study curcumin (Cur) release (Max = 69.32%, Min = 49.32%), and Cur release kinetics followed the Hixson-Crowell model. Fibroblast (3T3) cell lines were employed to determine the cell viability and proliferation to bioactive hydrogels. Antibacterial activities of bioactive hydrogels were evaluated against infection-causing bacterial strains. Bioactive hydrogels are hemocompatible due to their less than 0.5% hemolysis against fresh human blood. The results show that bioactive hydrogels can be potential wound dressing materials for wound healing applications.
  7. Khan R, Haider S, Khan MUA, Haider A, Razak SIA, Hasan A, et al.
    Int J Biol Macromol, 2023 Dec 31;253(Pt 5):127169.
    PMID: 37783243 DOI: 10.1016/j.ijbiomac.2023.127169
    The development of advanced multifunctional wound dressings remains a major challenge. Herein, a novel multilayer (ML) electrospun nanofibers (NFs) wound dressing based on diethylenetriamine (DETA) functionalized polyacrylonitrile (PAN), TiO2 nanoparticles (NPs) coating (Ct), and bioderived gelatin (Gel) was developed for potential applications in wound healing. The ML PAN-DETA-Ct-Gel membrane was developed by combining electrospinning, chemical functionalization, synthesis, and electrospray techniques, using a layer-by-layer method. The ML PAN-DETA-Ct-Gel membrane is comprised of an outer layer of PAN-DETA as a barrier to external microorganisms and structural support, an interlayer TiO2 NPs (Ct) as antibacterial function, and a contact layer (Gel) to improve biocompatibility and cell viability. The NFs membranes were characterized by scanning electron microscopy (SEM), surface profilometry, BET analysis, and water contact angle techniques to investigate their morphology, surface roughness, porosity, and wettability. The ML PAN-DETA-Ct-Gel wound dressing exhibited good surface roughness, porosity, and better wettability. Cell morphology, proliferation, and viability were determined using fibroblasts (3T3), and antibacterial assays were performed against six pathogens. The ML PAN-DETA-Ct-Gel NFs membrane showed good cell morphology, proliferation, viability, and antibacterial activity compared with other membranes. This new class of ML NFs membranes offers a multifunctional architecture with adequate biocompatibility, cell viability, and antibacterial activity.
  8. Khan MUA, Stojanović GM, Abdullah MFB, Dolatshahi-Pirouz A, Marei HE, Ashammakhi N, et al.
    Int J Biol Macromol, 2024 Jan;254(Pt 3):127882.
    PMID: 37951446 DOI: 10.1016/j.ijbiomac.2023.127882
    Tissue engineering is an advanced and potential biomedical approach to treat patients suffering from lost or failed an organ or tissue to repair and regenerate damaged tissues that increase life expectancy. The biopolymers have been used to fabricate smart hydrogels to repair damaged tissue as they imitate the extracellular matrix (ECM) with intricate structural and functional characteristics. These hydrogels offer desired and controllable qualities, such as tunable mechanical stiffness and strength, inherent adaptability and biocompatibility, swellability, and biodegradability, all crucial for tissue engineering. Smart hydrogels provide a superior cellular environment for tissue engineering, enabling the generation of cutting-edge synthetic tissues due to their special qualities, such as stimuli sensitivity and reactivity. Numerous review articles have presented the exceptional potential of hydrogels for various biomedical applications, including drug delivery, regenerative medicine, and tissue engineering. Still, it is essential to write a comprehensive review article on smart hydrogels that successfully addresses the essential challenging issues in tissue engineering. Hence, the recent development on smart hydrogel for state-of-the-art tissue engineering conferred progress, highlighting significant challenges and future perspectives. This review discusses recent advances in smart hydrogels fabricated from biological macromolecules and their use for advanced tissue engineering. It also provides critical insight, emphasizing future research directions and progress in tissue engineering.
  9. Sa'adon S, Ansari MNM, Razak SIA, Anand JS, Nayan NHM, Ismail AE, et al.
    Polymers (Basel), 2021 Jul 27;13(15).
    PMID: 34372062 DOI: 10.3390/polym13152459
    The aim of this study is to prepare a dual layer polyvinyl (PVA) patch using a combination of electrospinning techniques and cryogelation (freeze-thaw process) then subsequently to investigate the effect of freeze-thaw cycles, nanofiber thickness, and diclofenac sodium (DS) loading on the physicochemical and mechanical properties and formulation of dual layer PVA patches composed of electrospun PVA nanofibers and PVA cryogel. After the successful preparation of the dual layer PVA patch, the prepared patch was subjected to investigation to assess the effect of freeze-thaw cycles, nanofiber thickness and percentages of DS loading on the morphology, physiochemical and mechanical properties. Various spectroscopic techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), water contact angle, and tensile tests were used to evaluate the physicochemical and mechanical properties of prepared dual layer PVA patches. The morphological structures of the dual layer PVA patch demonstrated the effectiveness of both techniques. The effect of freeze-thaw cycles, nanofiber thickness, and DS percentage loading on the crystallinity of a dual layer PVA patch was investigated using XRD analysis. The presence of a distinct DS peak in the FTIR spectrum indicates the compatibility of DS in a dual layer PVA patch through in-situ loading. All prepared patches were considered highly hydrophilic because the data obtained was less than 90°. The increasing saturation of DS within the PVA matrix increases the tensile strength of prepared patches, however decreased its elasticity. Evidently, the increasing of electrospun PVA nanofibers thickness, freeze-thaw cycles, and the DS saturation has improved the physicochemical and mechanical properties of the DS medicated dual layer PVA patches, making them a promising biomaterial for transdermal drug delivery applications.
  10. Khan MUA, Yaqoob Z, Ansari MNM, Razak SIA, Raza MA, Sajjad A, et al.
    Polymers (Basel), 2021 Sep 16;13(18).
    PMID: 34578025 DOI: 10.3390/polym13183124
    The composite hydrogels were produced using the solution casting method due to the non-toxic and biocompatible nature of chitosan (CS)/polyvinyl alcohol (PVA). The best composition was chosen and crosslinked with tetraethyl orthosilicate (TEOS), after which different amounts of graphene oxide (GO) were added to develop composite hydrogels. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM) and contact angle was used to analyze the hydrogels. The samples were also evaluated for swelling abilities in various mediums. The drug release profile was studied in phosphate-buffered saline (PBS) at a pH of 7.4. To predict the mechanism of drug release, the data were fitted into kinetic models. Finally, antibacterial activity and cell viability data were obtained. FTIR studies revealed the successful synthesis of CS/PVA hydrogels and GO/CS/PVA in hydrogel composite. SEM showed no phase separation of the polymers, whereas AFM showed a decrease in surface roughness with an increase in GO content. 100 µL of crosslinker was the critical concentration at which the sample displayed excellent swelling and preserved its structure. Both the crosslinked and composite hydrogel showed good swelling. The most acceptable mechanism of drug release is diffusion-controlled, and it obeys Fick's law of diffusion for drug released. The best fitting of the zero-order, Hixson-Crowell and Higuchi models supported our assumption. The GO/CS/PVA hydrogel composite showed better antibacterial and cell viability behaviors. They can be better biomaterials in biomedical applications.
  11. Khan MUA, Al-Thebaiti MA, Hashmi MU, Aftab S, Abd Razak SI, Abu Hassan S, et al.
    Materials (Basel), 2020 Feb 21;13(4).
    PMID: 32098139 DOI: 10.3390/ma13040971
    Advancement and development in bone tissue engineering, particularly that of composite scaffolds, are of great importance for bone tissue engineering. We have synthesized polymeric matrix using biopolymer (β-glucan), acrylic acid, and nano-hydroxyapatite through free radical polymerization method. Bioactive nanocomposite scaffolds (BNSs) were fabricated using the freeze-drying method and Ag was coated by the dip-coating method. The scaffolds have been characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction analysis (XRD) to investigate their functional groups, surface morphology, and phase analysis, respectively. The pore size and porosity of all BNS samples were found to be dependent on silver concentration. Mechanical testing of all BNS samples have substantial compressive strength in dry form that is closer to cancellous bone. The samples of BNS showed substantial antibacterial effect against DH5 alpha E. coli. The biological studies conducted using the MC3T3-E1 cell line via neutral red dye assay on the scaffolds have found to be biocompatible and non-cytotoxic. These bioactive scaffolds can bring numerous applications for bone tissue repairs and regenerations.
  12. Khan MUA, Haider S, Raza MA, Shah SA, Razak SIA, Kadir MRA, et al.
    Int J Biol Macromol, 2021 Dec 01;192:820-831.
    PMID: 34648803 DOI: 10.1016/j.ijbiomac.2021.10.033
    Carbohydrate polymers are biological macromolecules that have sparked a lot of interest in wound healing due to their outstanding antibacterial properties and sustained drug release. Arabinoxylan (ARX), Chitosan (CS), and reduced graphene oxide (rGO) sheets were combined and crosslinked using tetraethyl orthosilicate (TEOS) as a crosslinker to fabricate composite hydrogels and assess their potential in wound dressing for skin wound healing. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and biological assays were used to evaluate the composite hydrogels. FTIR validated the effective fabrication of the composite hydrogels. The rough morphologies of the composite hydrogels were revealed by SEM and AFM (as evident from the Ra values). ATC-4 was discovered to have the roughest surface. TEM revealed strong homogeneous anchoring of the rGO to the polymer matrix. However, with higher amount of rGO agglomeration was detected. The % swelling at various pHs (1-13) revealed that the hydrogels were pH-sensitive. The controlled release profile for the antibacterial drug (Silver sulfadiazine) evaluated at various pH values (4.5, 6.8, and 7.4) in PBS solution and 37 °C using the Franz diffusion method revealed maximal drug release at pH 7.4 and 37 °C. The antibacterial efficacy of the composite hydrogels against pathogens that cause serious skin diseases varied. The MC3T3-E1 cell adhered, proliferated, and differentiated well on the composite hydrogels. MC3T3-E1 cell also illustrated excellent viability (91%) and proper cylindrical morphologies on the composite hydrogels. Hence, the composite hydrogels based on ARX, CS, and rGO are promising biomaterials for treating and caring for skin wounds.
  13. Khan MUA, Iqbal I, Ansari MNM, Razak SIA, Raza MA, Sajjad A, et al.
    Molecules, 2021 Sep 30;26(19).
    PMID: 34641480 DOI: 10.3390/molecules26195937
    The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels' crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker-Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R2 = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.
  14. Khan MUA, Abd Razak SI, Mehboob H, Abdul Kadir MR, Anand TJS, Inam F, et al.
    ACS Omega, 2021 Feb 16;6(6):4335-4346.
    PMID: 33623844 DOI: 10.1021/acsomega.0c05596
    In bone tissue engineering, multifunctional composite materials are very challenging. Bone tissue engineering is an innovative technique to develop biocompatible scaffolds with suitable orthopedic applications with enhanced antibacterial and mechanical properties. This research introduces a polymeric nanocomposite scaffold based on arabinoxylan-co-acrylic acid, nano-hydroxyapatite (nHAp), nano-aluminum oxide (nAl2O3), and graphene oxide (GO) by free-radical polymerization for the development of porous scaffolds using the freeze-drying technique. These polymeric nanocomposite scaffolds were coated with silver (Ag) nanoparticles to improve antibacterial activities. Together, nHAp, nAl2O3, and GO enhance the multifunctional properties of materials, which regulate their physicochemical and biomechanical properties. Results revealed that the Ag-coated polymeric nanocomposite scaffolds had excellent antibacterial properties and better microstructural properties. Regulated morphological properties and maximal antibacterial inhibition zones were found in the porous scaffolds with the increasing amount of GO. Moreover, the nanosystem and the polymeric matrix have improved the compressive strength (18.89 MPa) and Young's modulus (198.61 MPa) of scaffolds upon increasing the amount of GO. The biological activities of the scaffolds were investigated against the mouse preosteoblast cell lines (MC3T3-E1) and increasing the quantities of GO helps cell adherence and proliferation. Therefore, our findings showed that these silver-coated polymeric nanocomposite scaffolds have the potential for engineering bone tissue.
  15. Khan MUA, Raza MA, Razak SIA, Abdul Kadir MR, Haider A, Shah SA, et al.
    J Tissue Eng Regen Med, 2020 10;14(10):1488-1501.
    PMID: 32761978 DOI: 10.1002/term.3115
    It is a challenging task to develop active biomacromolecular wound dressing materials that are biocompatible and possesses antibacterial properties against the bacterial strains that cause severe skin disease. This work is focused on the preparation of a biocompatible and degradable hydrogel for wound dressing application using arabinoxylan (ARX) and guar gum (GG) natural polymers. Fourier transform infrared spectroscopy (FT-IR) confirmed that both ARX and GG interacted well with each other, and their interactions further increased with the addition of crosslinker tetraethyl orthosilicate. Scanning electron microscope (SEM) micrographs showed uniform porous morphologies of the hydrogels. The porous morphologies and uniform interconnected pores are attributed to the increased crosslinking of the hydrogel. Elastic modulus, tensile strength, and fracture strain of the hydrogels significantly improved (from ATG-1 to ATG-4) with crosslinking. Degradability tests showed that hydrogels lost maximum weight in 7 days. All the samples showed variation in swelling with pH. Maximum swelling was observed at pH 7. The hydrogel samples showed good antibacterial activity against Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) in PBS, good drug release profile (92% drug release), and nontoxic cellular behavior. The cells not only retained their cylindrical morphologies onto the hydrogel but were also performing their normal activities. It is, therefore, believed that as-developed hydrogel could be a potential material for wound dressing application.
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