Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia.

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.

Harnessing artificial intelligence-driven approach for enhanced indole-3-acetic acid from the newly isolated Streptomyces rutgersensis AW08.

Indole-3-acetic acid (IAA) derived from Actinobacteria fermentations on agro-wastes constitutes a safer and low-cost alternative to synthetic IAA. This study aims to select a high IAA-producing Streptomyces-like strain isolated from Lake Oubeira sediments (El Kala, Algeria) for further investigations (i.e., 16S rRNA gene barcoding and process optimization). Subsequently, artificial intelligence-based approaches were employed to maximize IAA bioproduction on spent coffee grounds as high-value-added feedstock. The specificity was the novel application of the Limited-Memory Broyden-Fletcher-Goldfarb-Shanno Box (L-BFGS-B) optimization algorithm. The new strain AW08 was a significant producer of IAA (26.116 ± 0.61 µg/mL) and was identified as Streptomyces rutgersensis by 16S rRNA gene barcoding and phylogenetic inquiry. The empirical data involved the inoculation of AW08 in various cultural conditions according to a four-factor Box Behnken Design matrix (BBD) of Response surface methodology (RSM). The input parameters and regression equation extracted from the RSM-BBD were the basis for implementing and training the L-BFGS-B algorithm. Upon training the model, the optimal conditions suggested by the BBD and L-BFGS-B algorithm were, respectively, L-Trp (X1) = 0.58 %; 0.57 %; T° (X2) = 26.37 °C; 28.19 °C; pH (X3) = 7.75; 8.59; and carbon source (X4) = 30 %; 33.29 %, with the predicted response IAA (Y) = 152.8; 169.18 µg/mL). Our findings emphasize the potential of the multifunctional S. rutgersensis AW08, isolated and reported for the first time in Algeria, as a robust producer of IAA. Validation investigations using the bioprocess parameters provided by the L-BFGS-B and the BBD-RSM models demonstrate the effectiveness of AI-driven optimization in maximizing IAA output by 5.43-fold and 4.2-fold, respectively. This study constitutes the first paper reporting a novel interdisciplinary approach and providing insights into biotechnological advancements. These results support for the first time a reasonable approach for valorizing spent coffee grounds as feedstock for sustainable and economic IAA production from S. rutgersensis AW08.

A comprehensive review of recent advances in the applications and biosynthesis of oxalic acid from bio-derived substrates.

Organic acids are important compounds with numerous applications in different industries. This work presents a comprehensive review of the biological synthesis of oxalic acid, an important organic acid with many industrial applications. Due to its important applications in pharmaceuticals, textiles, metal recovery, and chemical and metallurgical industries, the global demand for oxalic acid has increased. As a result, there is an increasing need to develop more environmentally friendly and economically attractive alternatives to chemical synthesis methods, which has led to an increased focus on microbial fermentation processes. This review discusses the specific strategies for microbial production of oxalic acid, focusing on the benefits of using bio-derived substrates to improve the economics of the process and promote a circular economy in comparison with chemical synthesis. This review provides a comprehensive analysis of the various fermentation methods, fermenting microorganisms, and the biochemistry of oxalic acid production. It also highlights key sustainability challenges and considerations related to oxalic acid biosynthesis, providing important direction for further research. By providing and critically analyzing the most recent information in the literature, this review serves as a comprehensive resource for understanding the biosynthesis of oxalic acid, addressing critical research gaps, and future advances in the field.

Protein by-products: Composition, extraction, and biomedical applications.

Significant upsurge in animal by-products such as skin, bones, wool, hides, feathers, and fats has become a global challenge and, if not properly disposed of, can spread contamination and viral diseases. Animal by-products are rich in proteins, which can be used as nutritional, pharmacologically functional ingredients, and biomedical materials. Therefore, recycling these abundant and renewable by-products and extracting high value-added components from them is a sustainable approach to reclaim animal by-products while addressing scarce landfill resources. This article appraises the most recent studies conducted in the last five years on animal-derived proteins' separation and biomedical application. The effort encompasses an introduction about the composition, an overview of the extraction and purification methods, and the broad range of biomedical applications of these ensuing proteins.

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.

Synthesis, surface modifications, and biomedical applications of carbon nanofibers: Electrospun vs vapor-grown carbon nanofibers.

Engineered nanostructures are materials with promising properties, enabled by precise design and fabrication, as well as size-dependent effects. Biomedical applications of nanomaterials in disease-specific prevention, diagnosis, treatment, and recovery monitoring require precise, specific, and sophisticated approaches to yield effective and long-lasting favorable outcomes for patients. In this regard, carbon nanofibers (CNFs) have been indentified due to their interesting properties, such as good mechanical strength, high electrical conductivity, and desirable morphological features. Broadly speaking, CNFs can be categorized as vapor-grown carbon nanofibers (VGCNFs) and carbonized CNFs (e.g., electrospun CNFs), which have distinct microstructure, morphologies, and physicochemical properties. In addition to their physicochemical properties, VGCNFs and electrospun CNFs have distinct performances in biomedicine and have their own pros and cons. Indeed, several review papers in the literature have summarized and discussed the different types of CNFs and their performances in the industrial, energy, and composites areas. Crucially however, there is room for a comprehensive review paper dealing with CNFs from a biomedical point of view. The present work therefore, explored various types of CNFs, their fabrication and surface modification methods, and their applications in the different branches of biomedical engineering.

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.

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.

Fabrication and Characterization of Nanocomposite Hydrogel Based on Alginate/Nano-Hydroxyapatite Loaded with Linum usitatissimum Extract as a Bone Tissue Engineering Scaffold.

In the current paper, we fabricated, characterized, and applied nanocomposite hydrogel based on alginate (Alg) and nano-hydroxyapatite (nHA) loaded with phenolic purified extracts from the aerial part of Linum usitatissimum (LOH) as the bone tissue engineering scaffold. nHA was synthesized based on the wet chemical technique/precipitation reaction and incorporated into Alg hydrogel as the filler via physical cross-linking. The characterizations (SEM, DLS, and Zeta potential) revealed that the synthesized nHA possess a plate-like shape with nanometric dimensions. The fabricated nanocomposite has a porous architecture with interconnected pores. The average pore size was in the range of 100-200 µm and the porosity range of 80-90%. The LOH release measurement showed that about 90% of the loaded drug was released within 12 h followed by a sustained release over 48 h. The in vitro assessments showed that the nanocomposite possesses significant antioxidant activity promoting bone regeneration. The hemolysis induction measurement showed that the nanocomposites were hemocompatible with negligible hemolysis induction. The cell viability/proliferation confirmed the biocompatibility of the nanocomposites, which induced proliferative effects in a dose-dependent manner. This study revealed the fabricated nanocomposites are bioactive and osteoactive applicable for bone tissue engineering applications.

Advances in Growth Factor Delivery for Bone Tissue Engineering.

Shortcomings related to the treatment of bone diseases and consequent tissue regeneration such as transplants have been addressed to some extent by tissue engineering and regenerative medicine. Tissue engineering has promoted structures that can simulate the extracellular matrix and are capable of guiding natural bone repair using signaling molecules to promote osteoinduction and angiogenesis essential in the formation of new bone tissues. Although recent studies on developing novel growth factor delivery systems for bone repair have attracted great attention, taking into account the complexity of the extracellular matrix, scaffolding and growth factors should not be explored independently. Consequently, systems that combine both concepts have great potential to promote the effectiveness of bone regeneration methods. In this review, recent developments in bone regeneration that simultaneously consider scaffolding and growth factors are covered in detail. The main emphasis in this overview is on delivery strategies that employ polymer-based scaffolds for spatiotemporal-controlled delivery of both single and multiple growth factors in bone-regeneration approaches. From clinical applications to creating alternative structural materials, bone tissue engineering has been advancing constantly, and it is relevant to regularly update related topics.

Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments.

After tooth loss, bone resorption is irreversible, leaving the area without adequate bone volume for successful implant treatment. Bone grafting is the only solution to reverse dental bone loss and is a well-accepted procedure required in one in every four dental implants. Research and development in materials, design and fabrication technologies have expanded over the years to achieve successful and long-lasting dental implants for tooth substitution. This review will critically present the various dental bone graft and substitute materials that have been used to achieve a successful dental implant. The article also reviews the properties of dental bone grafts and various dental bone substitutes that have been studied or are currently available commercially. The various classifications of bone grafts and substitutes, including natural and synthetic materials, are critically presented, and available commercial products in each category are discussed. Different bone substitute materials, including metals, ceramics, polymers, or their combinations, and their chemical, physical, and biocompatibility properties are explored. Limitations of the available materials are presented, and areas which require further research and development are highlighted. Tissue engineering hybrid constructions with enhanced bone regeneration ability, such as cell-based or growth factor-based bone substitutes, are discussed as an emerging area of development.

Imaging Constructs: The Rise of Iron Oxide Nanoparticles.

Over the last decade, an important challenge in nanomedicine imaging has been the work to design multifunctional agents that can be detected by single and/or multimodal techniques. Among the broad spectrum of nanoscale materials being investigated for imaging use, iron oxide nanoparticles have gained significant attention due to their intrinsic magnetic properties, low toxicity, large magnetic moments, superparamagnetic behaviour and large surface area-the latter being a particular advantage in its conjunction with specific moieties, dye molecules, and imaging probes. Tracers-based nanoparticles are promising candidates, since they combine synergistic advantages for non-invasive, highly sensitive, high-resolution, and quantitative imaging on different modalities. This study represents an overview of current advancements in magnetic materials with clinical potential that will hopefully provide an effective system for diagnosis in the near future. Further exploration is still needed to reveal their potential as promising candidates from simple functionalization of metal oxide nanomaterials up to medical imaging.

Silk fibroin nanoscaffolds for neural tissue engineering.

The nervous system is a crucial component of the body and damages to this system, either by injury or disease, can result in serious or potentially lethal consequences. An important problem in neural engineering is how we can stimulate the regeneration of damaged nervous tissue given its complex physiology and limited regenerative capacity. To regenerate damaged nervous tissue, this study electrospun three-dimensional nanoscaffolds (3DNSs) from a biomaterial blend of silk fibroin (SF), polyethylene glycol (PEG), and polyvinyl alcohol (PVA). The 3DNSs were characterised to ascertain their potential suitability for direct implant into the CNS. The biological activity of 3DNSs was investigated in vitro using PC12 cells and their effects on reactive astrogliosis were assessed in vivo using a photothrombotic model of ischaemic stroke in mice. Results showed that the concentration of SF directly affected the mechanical characteristics and internal structure of the 3DNSs, with formulations presenting as either a gel-like structure (SF ≥ 50%) or a nanofibrous structure (SF ≤ 40%). In vitro assessment revealed increased cell viability in the presence of the 3DNSs and in vivo assessment resulted in a significant decrease in glial fibrillary acidic protein (GFAP) expression in the peri-infarct region (p < 0.001 for F2 and p < 0.05 for F4) after stroke, suggesting that 3DNSs could be suppressing reactive astrogliosis. The findings enhanced our understanding of physiochemical interactions between SF, PEG, and PVA, and elucidated the potential of 3DNSs as a potential therapeutic approach to stroke recovery, especially if these are used in conjunction with drug or cell treatment.

Current and novel polymeric biomaterials for neural tissue engineering.

The nervous system is a crucial component of the body and damages to this system, either by of injury or disease, can result in serious or potentially lethal consequences. Restoring the damaged nervous system is a great challenge due to the complex physiology system and limited regenerative capacity.Polymers, either synthetic or natural in origin, have been extensively evaluated as a solution for restoring functions in damaged neural tissues. Polymers offer a wide range of versatility, in particular regarding shape and mechanical characteristics, and their biocompatibility is unmatched by other biomaterials, such as metals and ceramics. Several studies have shown that polymers can be shaped into suitable support structures, including nerve conduits, scaffolds, and electrospun matrices, capable of improving the regeneration of damaged neural tissues. In general, natural polymers offer the advantage of better biocompatibility and bioactivity, while synthetic or non-natural polymers have better mechanical properties and structural stability. Often, combinations of the two allow for the development of polymeric conduits able to mimic the native physiological environment of healthy neural tissues and, consequently, regulate cell behaviour and support the regeneration of injured nervous tissues.Currently, most of neural tissue engineering applications are in pre-clinical study, in particular for use in the central nervous system, however collagen polymer conduits aimed at regeneration of peripheral nerves have already been successfully tested in clinical trials.This review highlights different types of natural and synthetic polymers used in neural tissue engineering and their advantages and disadvantages for neural regeneration.

In situ-forming and pH-responsive hydrogel based on chitosan for vaginal delivery of therapeutic agents.

One of the important routes of drug administration for localized delivery of contraceptives and cervical cancer treatment agents is vaginal canal. Due to the low pH of vagina, a pH-responsive drug delivery system was developed. This hydrogel was synthesized based on a mucoadhesive biopolymer, chitosan (CS), that promotes the interaction between the hydrogel and mucosal surface of the vagina, potentially increasing the residence time of the system. This injectable hydrogel was formed via acid-labile Schiff-base linkages between free amine groups and aldehyde functionalities on modified chitosan. A novel approach was taken to add aldehyde functionalities to chitosan using a two-step reaction. Two types of slow and fast degrading hydrogels were prepared and loaded with iron (II) gluconate dihydrate, a non-hormonal spermicide, and doxorubicin hydrochloride, an anti-cancer drug. The release profiles of these drugs at different pH environments were assessed to determine the pH-dependent release mechanism. Mechanical properties, swell-ability and degradation rate of these matrices were studied. The cross-linking density of the hydrogel as well as pH changes played an important role in the characteristic of these hydrogels. The hydrogels degraded faster in lower pH, while the hydrogel with lower cross-linking density showed longer gelation time and faster degradation rate compared to the gel with higher cross-linking density. In vitro cytotoxicity assessment of these hydrogels in 48 h indicated the non-toxic effect of these hydrogels toward mesenchymal stem cells (MSCs) in the test period.

Graphene-Based Engineered Living Materials.

With the rise of engineered living materials (ELMs) as innovative, sustainable and smart systems for diverse engineering and biological applications, global interest in advancing ELMs is on the rise. Graphene-based nanostructures can serve as effective tools to fabricate ELMs. By using graphene-based materials as building units and microorganisms as the designers of the end materials, next-generation ELMs can be engineered with the structural properties of graphene-based materials and the inherent properties of the microorganisms. However, some challenges need to be addressed to fully take advantage of graphene-based nanostructures for the design of next-generation ELMs. This work covers the latest advances in the fabrication and application of graphene-based ELMs. Fabrication strategies of graphene-based ELMs are first categorized, followed by a systematic investigation of the advantages and disadvantages within each category. Next, the potential applications of graphene-based ELMs are covered. Moreover, the challenges associated with fabrication of next-generation graphene-based ELMs are identified and discussed. Based on a comprehensive overview of the literature, the primary challenge limiting the integration of graphene-based nanostructures in ELMs is nanotoxicity arising from synthetic and structural parameters. Finally, we present possible design principles to potentially address these challenges.

Core-shell structured microneedles with programmed drug release functions for prolonged hyperuricemia management.

An appropriate non-oral platform via transdermal delivery of drugs is highly recommended for the treatment of hyperuricemia. Herein, a core-shell structured microneedle patch with programmed drug release functions was designed to regulate serum uric acid (SUA) levels for prolonged hyperuricemia management. The patch was fabricated using a three-step casting method. Allopurinol (AP), an anti-hyperuricemic drug, was encapsulated within the carboxymethyl cellulose (CMC) layer, forming the "shell" of the MNs. The MN's inner core was composed of polyvinylpyrrolidone (PVP) loaded with urate oxidase-calcium peroxide nanoparticles (UOx-CaO2 NPs). When the as-fabricated core-shell structured microneedles were inserted into the skin, the loaded AP was first released immediately to effectively inhibit the production of SUA due to the water solubility of CMC. Subsequently, the internal SUA was further metabolized by UOx, leading to exposure of CaO2 NPs. The sustained release of UOx accompanied by the decomposition of CaO2 NPs contributed to maintaining a state of normal uric acid levels over an extended period. More attractively, uric acid could be oxidized due to the strong oxidant of CaO2, which was beneficial to the continuous consumption of uric acid. In vivo results showed that the as-fabricated MNs exhibited an excellent anti-hyperuricemia effect to reduce SUA levels to the normal state within 3 h and maintain the normouricemia state for 12 h. In addition, the levels of creatinine (Cr) and blood urea nitrogen (BUN) in the serum remained within the normal range, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) in the liver were effectively inhabited, mitigating the risk of liver and kidney damage for clinical anti-hyperuricemia management.

Starch biocomposites preparation by incorporating organosolv lignins from potato crop residues.

Plastic wastes accumulated due to food packaging pose environmental threats. This study proposes biopolymeric films containing lignins extracted from potato crop residues (PCR) through organosolv treatment as a green alternative to non-degradable food packaging. The isolation process yielded 43.9 wt% lignins with a recovery rate of 73.5 wt% achieved under optimum conditions at 180 °C with 50 % v/v ethanol. The extracted lignins were then incorporated into a starch matrix to create biocomposite films. ATR-FTIR analysis confirmed interactions between the starch matrix and extracted lignins, and XRD analysis showed the amorphous structure of lignins, reducing film crystallinity. The addition of 1 wt% of extracted lignins resulted in a 87 % reduction in oxygen permeability, a 25 % increase in the thermal stability of the film, and a 78 % enhancement in antioxidant. Furthermore, introducing 3 wt% lignins led to the lowest water vapor transmission rate, measuring 9.3 × 10-7 kg/s·m2. Morphological studies of the films demonstrated a homogeneous and continuous structure on both the surface and cross-sectional areas when the lignins content was below 7 wt%. These findings highlight the potential of using organosolv lignins derived from potato crop residues as a promising additive for developing eco-friendly films designed for sustainable food packaging.

Red Blood Cell Membrane-Camouflaged Polydopamine and Bioactive Glass Composite Nanoformulation for Combined Chemo/Chemodynamic/Photothermal Therapy.

Combinations of different therapeutic strategies, including chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT), are needed to effectively address evolving drug resistance and the adverse effects of traditional cancer treatment. Herein, a camouflage composite nanoformulation (TCBG@PR), an antitumor agent (tubercidin, Tub) loaded into Cu-doped bioactive glasses (CBGs) and subsequently camouflaged by polydopamine (PDA), and red blood cell membranes (RBCm), was successfully constructed for targeted and synergetic antitumor therapies by combining CT of Tub, CDT of doped copper ions, and PTT of PDA. In addition, the TCBG@PRs composite nanoformulation was camouflaged with a red blood cell membrane (RBCm) to improve biocompatibility, longer blood retention times, and excellent cellular uptake properties. It integrated with long circulation and multimodal synergistic treatment (CT, CDT, and PTT) with the benefit of RBCms to avoid immune clearance for efficient targeted delivery to tumor locations, producing an "all-in-one" nanoplatform. In vivo results showed that the TCBG@PRs composite nanoformulation prolonged blood circulation and improved tumor accumulation. The combination of CT, CDT, and PTT therapies enhanced the antitumor therapeutic activity, and light-triggered drug release reduced systematic toxicity and increased synergistic antitumor effects.

Facile preparation of self-healing hydrogels based on chitosan and PVA with the incorporation of curcumin-loaded micelles for wound dressings.

The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing.