Waste valorization as low-cost media engineering for auxin production from the newly isolated Streptomyces rubrogriseus AW22: Model development.

Indole-3-acetic acid (IAA) represents a crucial phytohormone regulating specific tropic responses in plants and functions as a chemical signal between plant hosts and their symbionts. The Actinobacteria strain of AW22 with high IAA production ability was isolated in Algeria for the first time and was characterized as Streptomyces rubrogriseus through chemotaxonomic analysis and 16 S rDNA sequence alignment. The suitable medium for a maximum IAA yield was engineered in vitro and in silico using machine learning-assisted modeling. The primary low-cost feedstocks consisted of various concentrations of spent coffee grounds (SCGs) and carob bean grounds (CBGs) extracts. Further, we combined the Box-Behnken design from response surface methodology (BBD-RSM) with artificial neural networks (ANNs) coupled with the genetic algorithm (GA). The critical process parameters screened via Plackett-Burman design (PBD) served as BBD and ANN-GA inputs, with IAA yield as the output variable. Analysis of the putative IAA using thin-layer chromatography (TLC) and (HPLC) revealed RF values equal to 0.69 and a retention time of 3.711 min, equivalent to the authentic IAA. AW 22 achieved a maximum IAA yield of 188.290 ±â€¯0,38 µg/mL using the process parameters generated by the ANN-GA model, consisting of L-Trp, 0.6%; SCG, 30%; T°, 25.8 °C; and pH 9, after eight days of incubation. An R2 of 99,98%, adding to an MSE of 1.86 × 10-5 at 129 epochs, postulated higher reliability of ANN-GA-approach in predicting responses, compared with BBD-RSM modeling exhibiting an R2 of 76,28%. The validation experiments resulted in a 4,55-fold and 4,46-fold increase in IAA secretion, corresponding to ANN-GA and BBD-RSM models, respectively, confirming the validity of both models.

MSCs-laden silk Fibroin/GelMA hydrogels with incorporation of platelet-rich plasma for chondrogenic construct.

Repair of osteochondral defects and regeneration of cartilage is a major challenge. In this work, the mesenchymal stem cells (MSCs)-laden hydrogel was designed using silk fibroin (SF) and gelatin methacrylate (GelMA), to encapsulate platelet-rich plasma (PRP). Initially, GelMA was synthesized, and SF was prepared using silkworm cocoon, then MSCs-laden SF/GelMA (SG) hydrogel was fabricated. The physicochemical properties of the hydrogels were evaluated using Fourier-transform infrared spectroscopy, scanning electron microscope, and rheometry. After hydrogel preparation, the viability of MSCs in the hydrogels was investigated via CCK-8 analysis and fluorescent images. The MSCs-laden SG hydrogel containing PRP was subsequently injected into the cartilage defect area in Sprague Dawley rats. Hematoxylin and eosin (H&E), Masson staining, and Mankin scores evaluation confirmed the new cartilage formation in 8 weeks. The results presented in the study, therefore, showed that the prepared MSCs-laden SG hydrogel loaded with PRP has the potential for cartilage reconstruction, which is crucial to the treatment of knee osteoarthritis.

Fabrication and desired properties of conductive hydrogel dressings for wound healing.

Conductive hydrogels are platforms recognized as constituting promising materials for tissue engineering applications. This is because such conductive hydrogels are characterized by the inherent conductivity properties while retaining favorable biocompatibility and mechanical properties. These conductive hydrogels can be particularly useful in enhancing wound healing since their favorable conductivity can promote the transport of essential ions for wound healing via the imposition of a so-called transepithelial potential. Other valuable properties of these conductive hydrogels, such as wound monitoring, stimuli-response etc., are also discussed in this study. Crucially, the properties of conductive hydrogels, such as 3D printability and monitoring properties, suggest the possibility of its use as an alternative wound dressing to traditional dressings such as bandages. This review, therefore, seeks to comprehensively explore the functionality of conductive hydrogels in wound healing, types of conductive hydrogels and their preparation strategies and crucial properties of hydrogels. This review will also assess the limitations of conductive hydrogels and future perspectives, with an emphasis on the development trend for conductive hydrogel uses in wound dressing fabrication for subsequent clinical applications.

Carbon nanotubes as a nitric oxide nano-reservoir improved the controlled release profile in 3D printed biodegradable vascular grafts.

Small diameter vascular grafts (SDVGs) are associated with a high failure rate due to poor endothelialization. The incorporation of a nitric oxide (NO) releasing system improves biocompatibility by using the NO effect to promote endothelial cell (EC) migration and proliferation while preventing bacterial infection. To circumvent the instability of NO donors and to prolong NO releasing, S-nitroso-N-acetyl-D-penicillamine (SNAP) as a NO donor was loaded in multi-walled carbon nanotubes (MWCNTs). Successful loading was confirmed with a maximum SNAP amount of ~ 5% (w/w) by TEM, CHNS analysis and FTIR spectra. SDVGs were 3D printed from polycaprolactone (PCL) and coated with a 1:1 ratio of polyethylene glycol and PCL dopped with different concentrations of SNAP-loaded matrix and combinations of MWCNTs-OH. Coating with 10% (w/w) SNAP-matrix-10% (w/w) SNAP-MWCNT-OH showed a diminished burst release and 18 days of NO release in the range of 0.5-4 × 10-10 mol cm-2 min-1 similar to the NO release from healthy endothelium. NO-releasing SDVGs were cytocompatible, significantly enhanced EC proliferation and migration and diminished bacterial viability. The newly developed SNAP-loaded MWCNT-OH has a great potential to develop NO releasing biomaterials with a prolonged, controlled NO release promoting in-situ endothelialization and tissue integration in vivo, even as an approach towards personalized medicine.

Injectable, self-healing, transparent, and antibacterial hydrogels based on chitosan and dextran for wound dressings.

One major shortcoming of biopolymeric based wound dressing so far is the lack of an integrated multi-functional system that could provide suitable mechanical strength, fast self-healing, transparency, antibacterial and antioxidant effects. Benefiting from the dynamic and rapid reaction between glycidyl trimethyl ammonium chloride-graft- chitosan (QCS) and aldehyde-dextran (ODex) under physiological conditions, we designed hydrogels (QCS-ODex) with fast in situ gel-forming (< 70 s), porous structure (300-350 µm), stable storage modulus and the loss modulus, suitable swelling capacity (2.465 folds of chitosan), tissue adhesion, transmission property, free radical scavenging capacity, good self-healing behavior, and injectability, inherent antibacterial (against E. coli and S. aureus) and biocompatibility. Furthermore, Baicalein could be in situ encapsulated into QCS-ODex hydrogels, and the release behavior of Baicalein could be regulated by adjusting the ratio of QCS and ODex. The Baicalein-loaded QCS-ODex hydrogel further facilitated free radical scavenging and antibacterial bioactivities due to the cooperative therapeutic effects between QCS-ODex and Baicalein. This study may provide new insights into designing multi-functional QCS-ODex hydrogels with multiple therapeutic effects as a wound dressing.

Improved anti-inflammatory properties of xanthan gum hydrogel physically and chemically modified with yeast derived peptide.

Bioactive peptides from natural resources with associated beneficial biological properties such as skin wound healing have drawn much attention. Polysaccharides with their biocompatibility, biodegradability, and ease of modification are suitable carriers for peptides delivery to the wound. In this study, a polysaccharide-peptide system was designed for potential wound healing applications. Xanthan hydrogels were modified with the yeast-derived peptide VW-9 with known biological properties via chemical conjugation using carbodiimide chemistry (XG-g-VW-9) or physically incorporation (XG-p-VW-9). Grafting VW-9 to the hydrogels increased the hydrogels' swelling degree and the release of the peptide from the hydrogels followed the Higuchi model indicating the peptide diffusion from the hydrogel matrix without hydrogel matrix dissolution. Both hydrogels were cytocompatible toward the tested fibroblast and macrophage cells. XG-p-VW-9 and XG-g-VW-9 reduce the level of tumor necrosis factor-alpha and interleukin-6 in cells activated with lipopolysaccharide more efficiently than free VW-9. Thus, VW-9-modified xanthan hydrogels may have the potential to be considered for skin wound healing.

Porcupine-inspired microneedles coupled with an adhesive back patching as dressing for accelerating diabetic wound healing.

Diabetes chronic wound is a severe and frequently occurring medical issue in patients with diabetes that often leads to more serious complications. Microneedles (MNs) can be used for wound healing as they can effectively pierce the epidermis and inject drugs into the wound tissue. However, common MN patches cannot provide sufficient skin adhesion to prevent detachment from the wound area. Inspired by the barb hangnail microstructure of porcupine quills, a porcupine quill-like multilayer MN patch with an adhesive back patching for tissue adhesion and diabetic wound healing was designed. Sodium hyaluronate-modified CaO2 nanoparticles and metformin (hypoglycemic agent) were loaded into the polycaprolactone tips of MNs, endowing them with exceptional antibacterial ability and hypoglycemic effect. A flexible and adhesive back patching was formed by polyacrylamide-polydopamine/Cu2+ composite hydrogel, which ensures that the MN patches do not peel off from the application sites and reduce bacterial infection. The bioinspired multilayer structure of MN patches exhibits satisfactory mechanical and antibacterial properties, which is a potential multifunctional dressing platform for promoting wound healing. STATEMENT OF SIGNIFICANCE: The porcupine quill-like microneedles (MNs) with PAM-PDA/Cu2+ (PPC) composite hydrogel back patching have been fabricated, which can enhance the adhesion property of MNs to the skin through a physical interlock of multilayer MNs and chemical bonding of hydrogel patching. CaO2-HA NPs and metformin were loaded into the polycaprolactone tips of MNs, endowing them with the exceptional antibacterial ability and hypoglycemic effect, which could accelerate diabetic wound healing. As a safe and effective strategy in transdermal delivery of drugs, the as-fabricated flexible multilayer MN patch with good antibacterial, hypoglycemic, and biocompatibility has been used to promote the healing of diabetic wound by releasing oxygen and inhibiting inflammation at the wound site.

Printable hyaluronic acid hydrogel functionalized with yeast-derived peptide for skin wound healing.

Targeted delivery of bioactive agents, growth factors, and drugs to skin wounds is a growing trend in biomaterials development for wound healing. This study presents a printable hyaluronic acid (HA) based hydrogel to deliver yeast-derived ACE-inhibitory peptide of VLSTSFPPW (VW-9) to the wound site. We first conjugated tyramine (Ty) on the carboxyl groups of the HA to form a phenol-functionalized HA (HA-Ty); then, the carboxylic acid groups of HA-Ty were aminated with ethylenediamine (HA-Ty-NH2). The primary amine groups of the HA-Ty-NH2 could then react with the carboxylic acids of the peptide. The hydrogel was then 3D printed and crosslinked with visible light. The modification of HA was confirmed by 1H NMR and FTIR. The swelling capacity of the conjugated hydrogels was 1.5-fold higher compared to the HA-Ty-NH2 hydrogel. The conjugated peptide did not affect on rheological properties and morphology of the hydrogels. The 3T3-L1 fibroblast cells seeded on the peptide-modified hydrogels exhibited higher viability than the hydrogels without the peptide, indicating that the peptide-enriched hydrogels may have the potential for wound healing applications.

Transdermal delivery of allopurinol to acute hyperuricemic mice via polymer microneedles for the regulation of serum uric acid levels.

Allopurinol (AP) is widely used to treat hyperuricemia which may cause severe side effects upon oral administration. Alternative means for the treatment of hyperuricemia are demanded to simultaneously facilitate drug absorption, patient compliance, and fewer side effects. In this study, a new polymer microneedle (MN) system was developed for the transdermal delivery of AP to acute hyperuricemic mice. This study aims to achieve the controllable regulation of serum uric acid (SUA) levels with fewer side effects compared with oral administration. The matrix of polymer MNs consisted of polyvinylpyrrolidone (PVP) and polycaprolactone (PCL), in which the rapid dissolution of PVP offers a rapid dissolution of AP into the blood and the biodegradability of PCL resulting in a sustainable drug release behavior. An in vivo study demonstrated that the AP-loaded MN system can effectively reduce the SUA levels as oral administration with lower side effects, which will be conducive to reducing the adverse reactions and improving the bioavailability of AP. This MN-mediated strategy can facilitate transcutaneous hyperuricemia treatment and provide a new alternative for the exploration of clinical treatment of hyperuricemia and improvement of patient compliance.

Chemical Composition, Antioxidant Activity and Cytocompatibility of Polyphenolic Compounds Extracted from Food Industry Apple Waste: Potential in Biomedical Application.

Apple pomace (AP) from the food industry is a mixture of different fractions containing bioactive polyphenolic compounds. This study provides a systematic approach toward the recovery and evaluation of the physiochemical and biological properties of polyphenolic compounds from AP. We studied subcritical water extraction (SCW) and solvent extraction with ethanol from four different AP fractions of pulp, peel, seed, core, and stem (A), peel (B), seed and core (C), and pulp and peel (D). The subcritical water method at the optimum condition resulted in total polyphenolic compounds (TPC) of 39.08 ± 1.10 mg GAE per g of AP on a dry basis compared to the ethanol extraction with TPC content of 10.78 ± 0.94 mg GAE/g db. Phloridzin, chlorogenic acid, and quercetin were the main identified polyphenolics in the AP fractions using HPLC. DPPH radical scavenging activity of fraction B and subcritical water (SW) extracts showed comparable activity to ascorbic acid while all ethanolic extracts were cytocompatible toward human fibroblast (3T3-L1) and salivary gland acinar cells (NS-SV-AC). Our results indicated that AP is a rich source of polyphenolics with the potential for biomedical applications.

Fabrication, characterization and biological properties evaluation of bioactive scaffold based on mineralized carbon nanofibers.

Tissue engineering as an innovative approach aims to combine engineering, biomaterials and biomedicine to eliminate the drawbacks of conventional bone defect treatment. In the current study, we fabricated bioengineered electroactive and bioactive mineralized carbon nanofibers as the scaffold for bone tissue engineering applications. The scaffold was fabricated using the sol-gel method and thoroughly characterized by SEM imaging, EDX analysis and a 4-point probe. The results showed that the CNFs have a diameter of 200 ± 19 nm and electrical conductivity of 1.02 ± 0.12 S cm-1. The in vitro studies revealed that the synthesized CNFs were osteoactive and supported the mineral crystal deposition. The hemolysis study confirmed the hemocompatibility of the CNFs and cell viability/proliferation sassy using an MTT assay kit showed the proliferative activities of mineralized CNFs. In conclusion, this study revealed that the mineralized CNFs synthesized by the combination of sol-gel and electrospinning techniques were electroactive, osteoactive and biocompatible, which can be considered an effective bone tissue engineering scaffold.Communicated by Ramaswamy H. Sarma.

Evaluation of two fungal exopolysaccharides as potential biomaterials for wound healing applications.

Microbial exopolysaccharides (EPSs) are mostly produced by bacteria and fungi and have potential use in the production of biomedical products such as nutraceuticals and in tissue engineering applications. The present study investigated the in vitro biological activities and in vivo wound healing effects of EPSs produced from a Sclerotium-forming fungus (Sclerotium glucanicum DSM 2159) and a yeast (Rhodosporidium babjevae), denoted as scleroglucan (Scl) and EPS-R, respectively. EPS yields of 0.9 ± 0.07 g/L and 1.11 ± 0.4 g/L were obtained from S. glucanicum and R. babjevae, respectively. The physicochemical properties of the EPSs were characterized using infrared spectroscopy and scanning electron microscopy. Further investigations of the biological properties showed that both EPSs were cytocompatible toward the human fibroblast cell line and demonstrated  hemocompatibility. Favorable wound healing capacities of the EPSs (10 mg/mL) were also established via in vivo tests. The present study therefore showed that the EPSs produced by S. glucanicum and R. babjevae have the potential use as biocompatible components for the promotion of dermal wound healing.

Enzymatically crosslinked hydrogel based on tyramine modified gelatin and sialylated chitosan.

The enzymatically crosslinked hydrogel could replicate the cellular microenvironment for biomedical applications. In the present study, to improve the cytocompatibility of chitosan (CS), sialic acid (SA) was introduced to CS to synthesize sialylated CS (CS-SA), and the tyramine (TA) was grafted to gelatin (G) to obtain TA modified gelatin (G-TA). The successful synthesis of CS-SA and G-TA was confirmed using1H NMR and UV-Vis absorption spectra. The interpenetrating polymer networks G-TA/CS-SA (GC) hydrogel was then fabricated via blending G-TA and CS-SA solutions and crosslinked using horseradish peroxidase. The storage modulus (G') of the fabricated GC hydrogels with different ratios of G-TA/CS-SA greatly varied during the formation and strain of hydrogels. With the increase of CS-SA concentration from 0% to 2%, the storage modulus of GC hydrogels was also observed to decrease from 1500 Pa to 101 Pa; the water uptake capacity of GC hydrogels increased from 1000% to 4500%. Additionally, the cell counting kit-8 and fluorescent images demonstrated the excellent cytocompatibility of GC hydrogels after culturing with NIH 3T3 cells. The obtained results indicated that the fabricated GC hydrogels might have potential in biomedical fields, such as wound dressing.

Thermochemical Liquefaction of Pomace Using Sub/Supercritical Ethanol: an Integrated Experimental and Preliminary Economic Feasibility Study.

Fossil sourced chemicals such as aromatics, are widely employed in the chemical industry for the production of commodity items. Recognizing the un-sustainability of existing approaches in the production of these chemicals, the current study investigated the valorization of apple pomace (AP) for their production. The present study assessed AP valorization by imposing variations in processing conditions of temperature (100-260 °C), time (0.5-12 h), alcohol/water ratio v/v (0:1-1:0), and Fe3+/H2O2 molar ratio (10:1-100-1), in accordance to the Box-Behnken experimental design. The optimal yield of the oil was 24.6 wt.%, at the temperature, time, alcohol/water ratio v/v, and Fe3+/H2O2 molar ratio of 260 °C, 4.7 h, 1, and 100, respectively. Notably, the application of gas chromatography-mass spectroscopy showed that the oil product contained mainly aromatics and interestingly also alkanes, indicating that the experimental conditions imposed promoted secondary hydrogenation reactions of oxygen-containing species during AP valorization. A consideration of the comparative economics of the proposed AP valorization and the existing AP management approach, using approximate estimation techniques, highlighted the potential of a ~ 59% reduction in the unit cost of AP management. The study therefore presents a compelling basis for future investigations into AP waste management using the thermochemical liquefaction technology.

Tannic acid post-treatment of enzymatically crosslinked chitosan-alginate hydrogels for biomedical applications.

Enzyme-mediated crosslinked hydrogels as soft materials for biomedical applications have gained considerable attention. In this article, we studied the effect of tannic acid post-treatment on adhesiveness and physiochemical properties of an enzymatically crosslinked hydrogel based on chitosan and alginate. The hydrogels were soaked in TA solution at different pH (3, 5.5, 7.4, and 9) and concentrations (1, 10, 20, 30 TA wt%). Increasing the TA concentration to 30 TA wt% and pH (up to 7.4) increased the TA loading and TA release. TA post-treatment reduced the swelling ratio and degradation rate of the hydrogels due to the formation of hydrogen bonding between TA molecules, chitosan, and alginate chains resulted in higher crosslinking density. TA-reinforced hydrogels with 30 % TA (Gel-TA 30) exhibited significantly high adhesive strength (up to 18 kPa), storage modulus (40 kPa), and antioxidant activity (>96 %), antibacterial activity, and proliferation and viability of 3 T3-L1 fibroblast cells.

Tannic acid: a versatile polyphenol for design of biomedical hydrogels.

Tannic acid (TA), a natural polyphenol, is a hydrolysable amphiphilic tannin derivative of gallic acid with several galloyl groups in its structure. Tannic acid interacts with various organic, inorganic, hydrophilic, and hydrophobic materials such as proteins and polysaccharides via hydrogen bonding, electrostatic, coordinative bonding, and hydrophobic interactions. Tannic acid has been studied for various biomedical applications as a natural crosslinker with anti-inflammatory, antibacterial, and anticancer activities. In this review, we focus on TA-based hydrogels for biomaterials engineering to help biomaterials scientists and engineers better realize TA's potential in the design and fabrication of novel hydrogel biomaterials. The interactions of TA with various natural or synthetic compounds are deliberated, discussing parameters that affect TA-material interactions thus providing a fundamental set of criteria for utilizing TA in hydrogels for tissue healing and regeneration. The review also discusses the merits and demerits of using TA in developing hydrogels either through direct incorporation in the hydrogel formulation or indirectly via immersing the final product in a TA solution. In general, TA is a natural bioactive molecule with diverse potential for engineering biomedical hydrogels.

Biosynthesis of exopolysaccharide from waste molasses using Pantoea sp. BCCS 001 GH: a kinetic and optimization study.

The bacterium Pantoea sp. BCCS 001 GH produces an exopolysaccharide (EPS) named Pantoan through using sugar beet molasses (SBM) as an inexpensive and widely available carbon source. This study aims to investigate the kinetics and optimization of the Pantoan biosynthesis using Pantoea sp. BCCS 001 GH in submerged culture. During kinetics studies, the logistic model and Luedeking-Piret equation are precisely fit with the obtained experimental data. The response surface methodology (RSM)-central composite design (CCD) method is applied to evaluate the effects of four factors (SBM, peptone, Na2HPO4, and Triton X-100) on the concentration of Pantoan in batch culture of Pantoea sp. BCCS 001 GH. The experimental and predicted maximum Pantoan production yields are found 9.9 ± 0.5 and 10.30 g/L, respectively, and the best prediction factor concentrations are achieved at 31.5 g/L SBM, 2.73 g/L peptone, 3 g/L Na2HPO4, and 0.32 g/L Triton X-100 after 48 h of submerged culture fermentation, at 30 °C. The functional groups and major monosaccharides (glucose and galactose) of a purified Pantoan are described and confirmed by 1HNMR and FTIR. The produced Pantoan is also characterized by thermogravimetric analysis and the rheological properties of the biopolymer are investigated. The present work guides the design and optimization of the Pantoea sp. BCCS 001 GH culture media, to be fine-tuned and applied to invaluable EPS, which can be applicable in food and biotechnology applications.

Exopolysaccharide from the yeast Papiliotrema terrestris PT22AV for skin wound healing.

INTRODUCTION: Exopolysaccharides (EPSs) are high-value functional biomaterials mainly produced by bacteria and fungi, with nutraceutical, therapeutic and industrial potentials. OBJECTIVES: This study sought to characterize and assess the biological properties of the EPS produced by the yeast Papiliotrema terrestris PT22AV. METHODS: After extracting the yeast's DNA and its molecular identification, the EPS from P. terrestris PT22AV strain was extracted and its physicochemical properties (structural, morphological, monosaccharide composition and molecular weight) were characterized. The EPS's in vitro biological activities and in vivo wound healing potential were also evaluated. RESULTS: The obtained EPS was water-soluble and revealed an average molecular weight (Mw) of 202 kDa. Mannose and glucose with 97% and 3% molar percentages, respectively, constituted the EPS. In vitro antibacterial activity analysis of the extracted EPS exhibited antibacterial activity (>80%) against Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis at a concentration of 2 mg/mL. The EPS showed cytocompatibility against the human fibroblast and macrophage cell lines and the animal studies showed a dose-dependent wound healing capacity of the EPS with higher wound closure at 10 mg/mL compared to negative and positive control after 14 days. CONCLUSION: The EPS from P. terrestris PT22AV could serve as a promising source of biocompatible macromolecules with potential for skin wound healing.

Bioengineering in salivary gland regeneration.

Salivary gland (SG) dysfunction impairs the life quality of many patients, such as patients with radiation therapy for head and neck cancer and patients with Sjögren's syndrome. Multiple SG engineering strategies have been considered for SG regeneration, repair, or whole organ replacement. An in-depth understanding of the development and differentiation of epithelial stem and progenitor cells niche during SG branching morphogenesis and signaling pathways involved in cell-cell communication constitute a prerequisite to the development of suitable bioengineering solutions. This review summarizes the essential bioengineering features to be considered to fabricate an engineered functional SG model using various cell types, biomaterials, active agents, and matrix fabrication methods. Furthermore, recent innovative and promising approaches to engineering SG models are described. Finally, this review discusses the different challenges and future perspectives in SG bioengineering.