Adipose-Derived Stem Cells (ADSCs) Loaded Gelatin-Sericin-Laminin Cryogels for Tissue Regeneration in Diabetic Wounds.

Healing in wounds like pressure ulcers, diabetic ulcers, venous ulcers, and arterial insufficiency ulcers is immensely hampered and causes both an economic burden and morbidity to patients. These wounds face a plethora of hostile conditions like elevated reactive oxygen species (ROS), impaired angiogenesis, senescent fibroblasts, and deficient stem cells that significantly diminish the probability of self-healing in these wounds. Adipose-derived stem cell therapy (ADSC) presents a promising approach to achieve efficient healing in such cases. To address the complex scenario of chronic wounds, we propose a combinatorial approach of delivering ADSCs on antioxidant gelatin-sericin (GS) scaffolds coated with laminin (GSL), an endothelial basement protein to improve angiogenesis. The synthesized GS scaffolds showed values of compression modulus, pore size, porosity, and the swelling ratio in the range of 65 kPa, 158 ± 48.8 µm, 91.1% ± 1.25, and 28 ± 2.5, respectively. A DPPH assay revealed GS scaffolds exhibit around 20% more scavenging as against gelatin (G) scaffolds and better protection against free radical assault, thus enhancing cell viability and the metabolic index of fibroblast cells. Different cells, namely, fibroblasts, keratinocytes, and ADSCs, cultured on GS scaffolds had better metabolic activity as compared with G scaffolds. Laminin coating onto the scaffolds leads to improved attachment and tube formation of endothelial cells as depicted in scanning electron microscopy images. Finally, we validated the applicability of the ADSCs loaded laminin-coated GS scaffolds in a diabetic ulcer rat model. Hematoxylin and eosin, Masson's trichrome, and picrosirius red staining showed better regeneration and collagen remodeling in ADSCs loaded GSL scaffolds. Immunostaining of CD31 staining demonstrates enhanced angiogenesis in GSL-ADSC as compared with other groups.

Entropically driven controlled release of paclitaxel from poly(2-ethyl-2-oxazoline) coated maghemite nanostructures for magnetically guided cancer therapy.

Theranostic nanostructures serve a dual purpose of therapy and diagnosis. A major fraction of these are based on polymer coated magnetic nanostructures of iron oxides (magnetite and maghemite), owing to the efficient drug loading capacity of polymer shells and enhanced magnetic contrast effects of the iron oxide core. In the current work we are proposing poly(2-ethyl-2-oxazoline) coated linear thermoresponsive nanostructures of maghemite (γ-Fe2O3) for potential application in targeted cancer therapy. The polymer coating was obtained via a modified sol-gel technique based on entropically driven phase separation of poly(2-ethyl-2-oxazoline) above its cloud point (CP) temperature of 63 °C in water. The developed nanostructures were further loaded with paclitaxel, a polar anticancer compound at room temperature (25 °C). The entropically driven release of paclitaxel at various concentrations and physiological temperatures was modeled and their application to the PC3 prostrate cancer cell line was investigated by treating in vitro. The steering efficiency of the magnetic nanostructures during their navigation through large blood vessels was also analyzed with the help of a synthetic model of the human axillary artery. The proposed application of these newly developed nanostructures can easily be extended towards localized delivery of additional polar anticancer drugs like cisplatin and doxorubicin.

Visible light-based 3D bioprinted composite scaffolds of κ-carrageenan for bone tissue engineering applications.

Three-dimensional (3D) printing of bone scaffolds using digital light processing (DLP) bioprinting technology empowers the treatment of patients suffering from bone disorders and defects through the fabrication of cell-laden patient-specific scaffolds. Here, we demonstrate the visible-light-induced photo-crosslinking of methacrylate-κ-carrageenan (MA-κ-CA) mixed with bioactive silica nanoparticles (BSNPs) to fabricate 3D composite hydrogels using digital light processing (DLP) printing. The 3D printing of complex bone structures, such as the gyroid, was demonstrated with high precision and resolution. DLP-printed 3D composite hydrogels of MA-κ-CA-BSNP were prepared and systematically assessed for their macroporous structure, swelling, and degradation characteristics. The viscosity, rheological, and mechanical properties were also investigated for the influence of nanoparticle incorporation in the MA-κ-CA hydrogels. The in vitro study performed with MC3T3-E1 pre-osteoblast-laden scaffolds of MA-κ-CA-BSNP revealed high cell viability, no cytotoxicity, and proliferation over 21 days with markedly enhanced osteogenic differentiation compared to neat polymeric scaffolds. Furthermore, no inflammation was observed in the 21-day study involving the in vivo examination of DLP-printed 3D composite scaffolds in a Wistar rat model. Overall, the observed results for the DLP-printed 3D composite scaffolds of MA-κ-CA and BSNP demonstrate their biocompatibility and suitability for bone tissue engineering.

Polysaccharide based transdermal patches for chronic wound healing: Recent advances and clinical perspective.

Polysaccharides form a major class of natural polymers with diverse applications in biomedical science and tissue engineering. One of the key thrust areas for polysaccharide materials is skin tissue engineering and regeneration, whose market is estimated to reach around 31 billion USD globally by 2030, with a compounded annual growth rate of 10.46 %. Out of this, chronic wound healing and management is a major concern, especially for underdeveloped and developing nations, mainly due to poor access to medical interventions for such societies. Polysaccharide materials have shown promising results and clinical potential in recent decades with regard to chronic wound healing. Their low cost, ease of fabrication, biodegradability, and ability to form hydrogels make them ideal candidates for managing and healing such difficult-to-heal wounds. The present review presents a summary of the recently explored polysaccharide-based transdermal patches for managing and healing chronic wounds. Their efficacy and potency of healing both as active and passive wound dressings are evaluated in several in-vitro and in-vivo models. Finally, their clinical performances and future challenges are summarized to draw a road map towards their role in advanced wound care.

Wire Arc Additive Manufacturing of Zinc as a Degradable Metallic Biomaterial.

Wire arc additive manufacturing (WAAM) offers a high rate of material deposition among various additive manufacturing techniques with wire as feedstock material but has not been established for zinc alloys. Zn alloys can be used as degradable biomaterials, in contrast to conventional permanent metallic biomaterials. In this work, commercially pure Zn was processed by WAAM to obtain near-dense parts, and the properties obtained through WAAM-processed Zn were compared with wrought (WR) Zn samples. The microstructure and hardness values of the WAAM (41 ± 1 HV0.3) components were found to be similar to those of the WR (35 ± 2 HV0.3) components. Bulk X-ray diffraction texture measurements suggested that WAAM builds exhibit a heavily textured microstructure compared to the WR counterparts, with peak intensities around <3 3−6 2> or <0 0 0 2> in the directions parallel to the build direction (BD). The corrosion rates in simulated body fluid (SBF) were similar for WAAM (0.45 mmpy) and WR (0.3 mmpy) samples. The weight loss measurements in SBF were found to be marginally higher in the WAAM samples compared to the WR counterparts for a duration of up to 21 days. MC3T3-E1 preosteoblasts were found to be healthy and proliferating in the culture medium containing the degradation products from WAAM-Zn in a manner similar to WR-Zn. This work establishes the feasibility of processing Zn by WAAM for use in bioresorbable metallic implants.

Red-emitting polyaniline-based nanoparticle probe for pH-sensitive fluorescence imaging.

Fluorescent probes based on semiconducting polymer nanoparticles (NPs) such as polyaniline (PANI) usually require external fluorophore doping to provide fluorescence function. Direct use of PANI-based NPs for bioimaging applications has been limited by PANI's weak blue fluorescence and aggregation-induced quenching in physiological medium. In this report, we developed a facile solid-state synthesis method to produce fluorescent polyaniline nanoparticles (FPNs) that are not only water-soluble but also exhibit high intensity and pH-sensitive red fluorescence. The FPNs showed high photoluminescence quantum yield (PLQY) of 19.3 % at physiological pH, which makes FPNs ideal for application as fluorescent nanoprobes in bioimaging. Moreover, we performed an in-depth study of photoluminescence dependence on pH and the phenomena of exciton-polaron quenching at low pH was highlighted. We also found that the ratio of emission intensity at 600 nm and 650 nm increased from 0.04 to 1.65 as pH was raised from 2.6 to 11.8, which could find its application in ratiometric pH sensing. FPNs exhibited excellent biocompatibility with >85 % cell viability for fibroblasts NIH/3 T3 and prostate cancer 22RV1 cells even at concentrations as high as 1000 µg/mL. In addition, fluorescence microscopy demonstrated concentration-dependent red fluorescence in the cytoplasm owing to the cellular uptake of FPNs in prostate cancer cells.

Agar-Iodine Transdermal Patches for Infected Diabetic Wounds.

In the present work, we have tested the potency of iodine-loaded agar transdermal patches (5 mg/cm2) for the treatment of infected diabetic wounds in the Wistar rat model. The rats were treated with the newly developed agar-iodine-potassium iodide (KI)-glycerol (AKIG) patch along with two other commercial dressings Iodoflex and Tegaderm as controls. Animals that received treatment with AKIG patches and Iodoflex showed better infection containment as compared to that with Tegaderm-covered control and exhibited complete healing. The antimicrobial property of all the patches was tested on three bacterial species-Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa-found in infected wounds. P. aeruginosa exhibited the highest minimum inhibitory concentration and minimum bactericidal concentration values among the three bacterial species for all the patches. The patch showed values of tensile strength, elongation, water vapor transmission rate, and swelling in the range of 34 ± 5 MPa, 51% ± 5, 2700 ± 110 g/m2/day, and 250% ± 25, respectively, for the agar-KI-iodine patch. The release kinetics of iodine through the agar matrix was found to follow the first-order drug release kinetics.

Synergistic effect of bacterial cellulose reinforcement and succinic acid crosslinking on the properties of agar.

In this work, the modification of agar is presented with the synergistic effect of bacterial cellulose reinforcement and succinic acid crosslinked agar. The effect of crosslinking agar with succinic acid on tensile strength and water absorption were studied. Crosslinking was confirmed with Fourier infrared spectroscopy. The tensile strength of agar was increased by 70% by succinic acid crosslinking (from55 ± 9.97 MPa to 93.40 ± 9.97 MPa) and the crosslinked agar absorbed only 18.66% water compared to uncrosslinked agar. The tensile strength of agar was increased by 56% by bacterial cellulose reinforcement (55 ± 9.97 MPa to 86.30 ± 14.70 MPa). The strength of agar was improved by 101% by the synergistic effect of bacterial cellulose reinforcement and succinic acid crosslinking (55 ± 9.97 MPa to 111 ± 12.30 MPa). Cytocompatibility studies of the developed films suggested that the crosslinked samples can also have potential applications in biomedical engineering apart from packaging applications.

Flexible agar-sericin hydrogel film dressing for chronic wounds.

Chronic wounds suffer impaired healing that results in psychological effect and morbity in addition to economic burden on the patient. These wounds are characterized by prolonged inflammatory phase, poor collagen production, hampered angiogenesis, upregulation in reactive oxygen species (ROS) and matrix metalloproteases (MMP). In the current work, three different concentrations (03:01, 05:01 and 10:01) of flexible agar-sericin-glycerol hydrogel films with sericin as minor component were fabricated to improve collagen production and capture free radical species to expediate chronic wound healing. The films exhibited improved collagen production with a p-value ≤ 0.001 for all the three concentrations. With regards to free radical scavenging, the 03:01 and 05:01 films exhibited improved performance with a p-value ≤ 0.01, while, 10:01 film showed improvement with a p-value ≤ 0.05. This was confirmed by Sirius red staining and 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay. In addition, these films showed an adequate tensile strength of around 35 MPa with elongation at break higher than 25%. The as cast films exhibited satisfactory swelling behavior of around 320% in simulated wound fluid (SWF).

Agarose bioplastic-based drug delivery system for surgical and wound dressings.

We have developed an agarose-based biocompatible drug delivery vehicle. The vehicle is in the form of thin, transparent, strong and flexible films. The biocompatibility and haemocompatibility of the films is confirmed using direct and indirect contact biological assay. Contact angle measurement exhibits hydrophilic nature of the films, and protein adsorption test shows low protein adsorption on the film surface. Drugs, antibiotics and antiseptics, retain their potency after their incorporation into the films. Our bioplastic films can be a versatile medium for drug delivery applications, especially as wound and surgical dressings where a fast drug release rate is desired.