The relentless pursuit of precision medicine has catalyzed the development of molecular and cellular tethered drug delivery systems, a burgeoning field that stands to redefine the paradigms of therapeutic delivery. This review encapsulates the cutting-edge advancements within this domain, emphasizing the engineering of molecular tethers and cellular vectors designed to ferry therapeutics directly to their target sites with unparalleled specificity and efficiency. By exploiting the unique biochemical signatures of disease states, these systems promise a substantial reduction in off-target effects and an enhancement in drug bioavailability, thereby mitigating the systemic side effects that are often associated with conventional drug therapies. Through a synthesis of recent research findings, this review highlights the innovative approaches being explored in the design and application of these tethered systems, ranging from nanotechnology-based solutions to genetically engineered cellular carriers. The potential of these systems to provide targeted therapy for a wide array of diseases, including cancer, autoimmune disorders, and neurological conditions, is thoroughly examined. This abstract aims to provide a succinct overview of the current state and future prospects of molecular and cellular tethered drug delivery systems in advancing the frontiers of precision medicine.

In tissue engineering (TE), the support structure (scaffold) plays a key role necessary for cell adhesion and proliferation. The protein constituents of the extracellular matrix (ECM), such as collagen, its derivative gelatine, and elastin, are the most attractive materials as possible scaffolds. To improve the modest mechanical properties of gelatine, a strategy consists of crosslinking it, as naturally occurs for collagen, which is stiffened by the oxidative action of lysyl oxidase (LO). Here, a novel protocol to crosslink gelatine has been developed, not using the commonly employed crosslinkers, but based on the formation of imine bonds or on aldolic condensation reactions occurring between gelatine and properly synthesized copolymers containing amine residues via LO-mediated oxidation. Particularly, we first synthesized and characterized an amino butyl styrene monomer (5), its copolymers with dimethylacrylamide (DMAA), and its terpolymer with DMAA and acrylic acid (AA). Three acryloyl amidoamine monomers (11a-c) and their copolymers with DMAA were then prepared. A methacrolein (MA)/DMAA copolymer already possessing the needed aldehyde groups was finally developed to investigate the relevance of LO in the crosslinking process. Oxidation tests of amine copolymers with LO were performed to identify the best substrates to be used in experiments of gelatine reticulation. Copolymers obtained with 5, 11b, and 11c were excellent substrates for LO and were employed with MA/DMAA copolymers in gelatine crosslinking tests in different conditions. Among the amine-containing copolymers, that obtained with 5 (CP5/DMMA-43.1) afforded a material (M21) with the highest crosslinking percentage (71%). Cytotoxicity experiments carried out on two cell lines (IMR-32 and SH SY5Y) with the analogous (P5) of the synthetic constituent of M21 (CP5/DMAA) had evidenced no significant reduction in cell viability, but proliferation promotion, thus establishing the biocompatibility of M21 and the possibility to develop it as a new scaffold for TE, upon further investigations.

Tuberculosis (TB) remains one of the most infectious pathogens with the highest human mortality and morbidity. Biofilm formation during Mycobacterium tuberculosis (Mtb) infection is responsible for bacterial growth, communication, and, most essentially, increased resistance/tolerance to antibiotics leading to higher bacterial persistence. Thus, biofilm growth is presently considered a key virulence factor in the case of chronic disease. Metal-Organic Frameworks (MOFs) have recently emerged as a highly efficient system to improve existing antibiotics' therapeutic efficacy and reduce adverse effects. In this regard, we have synthesized Cu-MOF (IITI-3) using a solvothermal approach. IITI-3 was well characterized by various spectroscopic techniques. Herein, IITI-3 was first encapsulated with isoniazid (INH) to form INH@IITI-3 with 10 wt% loading within 1 hour. INH@IITI-3 was well characterized by PXRD, TGA, FTIR, and BET surface area analysis. Furthermore, the drug release kinetics studies of INH@IITI-3 have been performed at pH 5.8 and 7.4 to mimic the small intestine and blood pH, respectively. The results show that drug release follows first-order kinetics. Furthermore, the antimycobacterial activity of INH@IITI-3 demonstrated significant bacterial killing and altered the structural morphology of the bacteria. Moreover, INH@IITI-3 was able to inhibit the mycobacterial biofilm formation upon treatment and showed less cytotoxicity toward the murine RAW264.7 macrophages. Thus, this work significantly opens up new possibilities for the applications of INH@IITI-3 in biofilm infections in Mtb and further contributes to TB therapeutics.

Non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive procedures and devices have been developed or are currently being investigated to enhance drug delivery across the BBB. This paper presents a review and a prospective analysis of the art and science that address pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Effective drug delivery to target sites is critical for achieving desired therapeutic outcomes. However, the poor permeability of certain drugs poses significant challenges in achieving adequate drug concentrations at the desired locations. Biomimetic hydrogels have emerged as a promising approach to enhance the penetration of poorly permeable drugs. These hydrogels, designed to mimic natural biological systems, offer unique properties and functionalities that enable improved drug permeation. In this review, we provide a comprehensive appraisal of the role of biomimetic hydrogels in enhancing drug penetration. We discuss the design principles, properties, and mechanisms by which these hydrogels facilitate drug permeation. Specifically, we explore the applications and benefits of biomimetic hydrogels in controlled drug release, mimicking extracellular matrix microenvironments, promoting cell-mimetic interactions, and enabling targeted drug delivery. Through an examination of key studies and advancements, we highlight the potential of biomimetic hydrogels in enhancing drug penetration and their implications for therapeutic interventions. This review contributes to a deeper understanding of biomimetic hydrogels as a promising strategy for overcoming drug penetration challenges and advancing drug delivery systems, ultimately leading to improved therapeutic efficacy.

The management and treatment of disease are achieved via the use of pharmacologically active substances or drugs. Drugs do not, however, have an intrinsic ability to be effective; rather, how well they work depends on how they are administered or supplied. Treatment of a variety of biological illnesses, such as autoimmune disorders, cancer, and bacterial infections, requires effective drug delivery. Drug absorption, distribution, metabolism, duration of therapeutic impact, pharmacokinetics, excretion, and toxicity can all be impacted by drug administration. Improved chemistry and materials are required for the delivery of therapeutic concentration of novel treatments to the specified targets within the body, as well as for the necessary duration of time. This requirement is accompanied by the development of new therapeutics. Formulating a medication as a DDS is a promising strategy for directly addressing numerous typical barriers to adherence, such as frequent dosage, such as frequent dosage, side effects, and a delayed beginning of the action. In the current review, we give a compendium of drug delivery and controlled release and subsequently highlight some of the newest developments in the realm, with a particular emphasis on cutting-edge methods for targeted therapy. In each instance, we outline the obstacles to efficient drug administration as well as the chemical and material developments that are allowing the sector to overcome these obstacles and have a positive clinical impact.

Autologous fat grafting is commonly used for soft-tissue repair (approximately 90,000 cases per year in the United States), but outcomes are limited by volume loss (20% to 80%) over time. Human allograft adipose matrix (AAM) stimulates de novo adipogenesis in vivo, but retention requires optimization. The extracellular matrix derived from superficial fascia, interstitial within the adipose layer, is typically removed during AAM processing. Thus, fascia, which contains numerous important proteins, might cooperate with AAM to stimulate de novo adipogenesis, improving long-term retention compared to AAM alone.

Human AAM and fascia matrix proteins (back and upper leg regions) were identified by mass spectrometry and annotated by gene ontology. A three-dimensional in vitro angiogenesis assay was performed. Finally, AAM and/or fascia (1 mL) was implanted into 6- to 8-week-old male Fischer rats. After 8 weeks, the authors assessed graft retention by gas pycnometry and angiogenesis (CD31) and adipocyte counts (hematoxylin and eosin) histologically.

Gene ontology annotation revealed an angiogenic enrichment pattern unique to the fascia, including lactadherin, collagen alpha-3(V) chain, and tenascin-C. In vitro, AAM stimulated 1.0 ± 0.17 angiogenic sprouts per bead. The addition of fascia matrix increased sprouting by 88% (2.0 ± 0.12; P < 0.001). A similar angiogenic response (CD31) was observed in vivo. Graft retention volume was 25% (0.25 ± 0.13) for AAM, significantly increasing to 60% (0.60 ± 0.14) for AAM/fascia ( P < 0.05). De novo adipogenesis was 12% (12.4 ± 7.4) for AAM, significantly increasing to 51% (51.2 ± 8.0) for AAM/fascia ( P < 0.001) by means of adipocyte quantification.

Combining fascia matrix with AAM improves angiogenesis and adipogenesis compared to AAM alone in rats. These preliminary in vitro and pilot animal studies should be further validated before definitive clinical adoption.

When producing an off-the-shelf adipose inducing product by adding a connective tissue fascial component (that is normally discarded) to the mix of adipose matrix, vasculogenesis is increased and, thus, adipogenesis and graft survival is improved. This is a significant advance in this line of product.

Bone replacement using porous and solid metallic implants, such as Ti-alloy implants, is regarded as one of the most practical therapeutic approaches in biomedical engineering. The bone is a complex tissue with various mechanical properties based on the site of action. Patient-specific Ti-6Al-4V constructs may address the key needs in bone treatment for having customized implants that mimic the complex structure of the natural tissue and diminish the risk of implant failure. This review focuses on the most promising methods of fabricating such patient-specific Ti-6Al-4V implants using additive manufacturing (AM) with a specific emphasis on the popular subcategory, which is powder bed fusion (PBF). Characteristics of the ideal implant to promote optimized tissue-implant interactions, as well as physical, mechanical/chemical treatments and modifications will be discussed. Accordingly, such investigations will be classified into 3B-based approaches (Biofunctionality, Bioactivity, and Biostability), which mainly govern native body response and ultimately the success in implantation.

Recent breakthroughs in the field of nanoparticle-based therapeutic delivery methods have changed the standpoint of cancer therapy by effectively delaying the process of disease development. Nanoparticles have a unique capacity of good penetrating ability than other therapeutic leads used in traditional therapeutics, and also, they have the highest impact on disease management. In the current study isolongifolene-loaded Chitosan nanoparticles have been formulated, synthesized and then characterized by the use of Fourier Transform Infrared Spectroscopy, X-ray Diffraction, Scanning Electron Microscopy and Transmission Electron Microscopy. Further, the characterized chitosan nano formulation was evaluated for hemocompatibility, plasma stability, and in-vitro release. Isolongifolene-loaded chitosan nanoparticles were found to be compatible with plasma and also, they exhibited a constant release pattern. Hence, chitosan-loaded nanoparticles could be employed as an excellent adjuvant in cancer therapeutic, to combat the multi-drug resistance in solid tumors.

Cancer nano-therapeutics are rapidly evolving and are often used to overcome a number of concerns with traditional drug delivery methods, including non-specific drug targeting and distribution, low oral bioavailability, and poor hydrophilicity. Modern nano-based targeting techniques have been developed as a result of advances in nano vehicle engineering and materials science, which may bring people with cancer a new hope. Clinical trials have been authorized for a number of medicinal nanocarriers. Nanocarriers with the best feasible size and surface attributes have been developed to optimize biodistribution and increase blood circulation duration. Nanotherapeutics can carry preloaded active medicine towards cancerous cells by preferentially leveraging the specific physiopathology of malignancies. In contrast to passive targeting, active targeting strategies involving antigens or ligands, developed against specific tumor sites, boost the selectivity of these curative nanovehicles. Another barrier that nanoparticles may resolve or lessen is drug resistance. Multifunctional and complex nanoparticles are currently being explored and are predicted to usher in a new era of nanoparticles that will allow for more individualized and customized cancer therapy. The potential prospects and opportunities of stimuli-triggered nanosystems in therapeutic trials are also explored in this review.

Long-term presence of M1 macrophages causes serious foreign body reaction (FBR), which is the main reason for the failure of biological scaffold integration. Inducing M2 polarization of macrophages near scaffolds to reduce foreign body response has been widely researched. In this work, inspired by the special capability of tumor exosomes in macrophages M2 polarization, we integrate tumor-derived exosomes into biological scaffolds to minimize the FBR. In brief, breast cancer cell-derived exosomes are loaded into polycaprolactone-b-polyethylene glycol-b-polycaprolactone (PCL-PEG-PCL) fiber scaffold through physical adsorption and entrapment to constructed bioactive engineered scaffold. In cellular experiments, we demonstrate bioactive engineered scaffold based on PCL-PEG-PCL and exosomes can promote the transformation of macrophages from M1 to M2 through the PI3K/Akt signaling pathway. In addition, the exosomes release gradually from scaffolds and act on the macrophages around the scaffolds to reduce FBR in a subcutaneous implant mouse model. Compared with PCL-PEG-PCL scaffolds without exosomes, bioactive engineered scaffolds reduce significantly inflammation and fibrosis of tissues around the scaffolds. Therefore, cancer cell-derived exosomes show the potential for constructing engineered scaffolds in inhibiting the excessive inflammation and facilitating tissue formation.

Until now, strategies used to treat cancer are imperfect, and this generates the need to search for better and safer solutions. The biggest issue is the lack of selective interaction with neoplastic cells, which is associated with occurrence of side effects and significantly reduces the effectiveness of therapies. The use of nanoparticles in cancer can counteract these problems. One of the most promising nanoparticles is magnetite. Implementation of this nanoparticle can improve various treatment methods such as hyperthermia, targeted drug delivery, cancer genotherapy, and protein therapy. In the first case, its feature makes magnetite useful in magnetic hyperthermia. Interaction of magnetite with the altered magnetic field generates heat. This process results in raised temperature only in a desired part of a patient body. In other therapies, magnetite-based nanoparticles could serve as a carrier for various types of therapeutic load. The magnetic field would direct the drug-related magnetite nanoparticles to the pathological site. Therefore, this material can be used in protein and gene therapy or drug delivery. Since the magnetite nanoparticle can be used in various types of cancer treatment, they are extensively studied. Herein, we summarize the latest finding on the applicability of the magnetite nanoparticles, also addressing the most critical problems faced by smart nanomedicine in oncological therapies.

Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells. Among others, methacrylated gelatin (GelMA) has become a representative hydrogel formulation, finding various biomedical applications. Recent efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials, aiming to provide enhanced physicochemical and biological properties to GelMA. The benefits of this approach are multiple: i) reinforcing mechanical properties, ii) modulating viscoelastic property to allow 3D printability of bio-inks, iii) rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues (e.g., muscle, nerve), iv) providing stimuli-responsiveness to actively deliver therapeutic molecules, and v) endowing therapeutic capacity in tissue repair process (e.g., antioxidant effects). The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues (bone, skin, cardiac, and nerve) that are rarely observable with GelMA. Here we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue therapeutics. The approaches used in GelMA can also apply to other existing polymeric hydrogel systems.

As a low cost, biocompatible, and bioresorbable synthetic polymer, poly (ɛ-caprolactone) (PCL) is widely used for different biomedical applications including drug delivery, wound dressing, and tissue engineering. An extensive range of in vitro and in vivo tests has proven the favourable applicability of PCL in biomedicine, bringing about the FDA approval for a plethora of PCL made medical or drug delivery systems. This popular polymer, widely researched since the 1970s, can be readily processed through various techniques such as 3D printing and electrospinning to create biomimetic and customized medical products. However, low mechanical strength, insufficient number of cellular recognition sites, poor bioactivity, and hydrophobicity are main shortcomings of PCL limiting its broader use for biomedical applications. To maintain and benefit from the high potential of PCL, yet addressing its physicochemical and biological challenges, blending with nature-derived (bio)polymers and incorporation of nanofillers have been extensively investigated. Here, we discuss novel additives that have been meant for enhancement of PCL nanofiber properties and thus for further extension of the PCL nanofiber application domain. The most recent researches (since 2017) have been covered and an updated overview about hybrid PCL nanofibers is presented with focus on those including nature-derived additives, e.g., polysaccharides and proteins, and synthetic additives, e.g., inorganic and carbon nanomaterials.

Motor neuron diseases are neurodegenerative diseases that predominantly affect the neuromuscular system. To date, there are no valid therapeutic treatments for such diseases, and the classical experimental models fail in faithfully reproducing the pathological mechanisms behind them. In this regard, the use of three-dimensional (3D) culture systems, which more closely reproduce the native in vivo environment, can be a promising approach. Hydrogel-based systems are among the most used materials to reproduce the extracellular matrix, featuring an intrinsic similarity with its physiological characteristics. In this study, we developed a thermosensitive chitosan-based hydrogel combined with β-glycerophosphate (βGP) and sodium hydrogen carbonate (SHC), which give the system optimal mechanical properties and injectability, inducing the hydrogel sol-gel transition at 37 °C. An ad hoc protocol for the preparation of the hydrogel was established in order to obtain a highly homogeneous system, leading to reproducible physicochemical characteristics and easy cell encapsulation. All formulations supported the viability of a neuroblastoma/spinal cord hybrid cell line (NSC-34) beyond two weeks of culture and enabled cell differentiation towards a motor neuron-like morphology, characterized by the presence of extended neurites. Based on our results, these hydrogels represent excellent candidates for establishing 3D in vitro models of motor neuron diseases.

The title compound, (NH4)4[W2(C10H12N2O8)O6]·4H2O, was obtained from a mixture of tungstic acid, ammonia and ethyl-enedi-amine-tetra-acetic acid (H4edta) in a 2:4:1 ratio. The anion of the complex contains two WO3 units and one bridging edta4- ligand. Each central metal atom is tridentately coordinated by nitro-gen and two carboxyl-ate groups of the edta4- ligand, together with the three oxido ligands, producing a distorted octa-hedral coordination environment around each tungsten atom. The center of the carbon-carbon bond of the ethyl-ene bridge represents a crystallographic inversion center. The crystal structure consists of a three-dimensional supra-molecular framework built up by the dinuclear cations, the ammonium counter-ions and the solvent water mol-ecules via hydrogen bonds of the N-H⋯O and O-H⋯O type.

Introduction: The use of herbal compounds in cancer therapy has great potential to promote the efficacy of current cancer therapeutic strategies. Herbal compounds were successfully reported to enhance tumor cells sensitization to the action of chemo-, hormonal- and gene-therapeutic agents via different mechanisms. Herbal ingredients can affect different signaling pathways, reduce the toxic side effects or inhibit the efflux of anticancer drugs.Areas covered: This review will discuss the delivery of herbal compounds with other cancer treatments such as hormonal, small molecule inhibitors and inorganic hybrids to tumor cells. An overview of physicochemical properties of herbal components that require intelligent design of combo-nanomedicines for efficient co-delivery of those herbal-derived and other anticancer agents was discussed. Nanocarriers provide various benefits to overcome the shortcomings of the encapsulated herbal compounds including improved solubility, increased stability and enhanced tumor targeting. Different nanocarrier systems were the focus of this review.Expert opinion: Multifunctional nanocarrier systems encapsulating herbal and different anticancer drugs showed to be a wonderful approach in the treatment of cancer enabling the co-delivery of anticancer drugs with versatile modes of action in an accurate manner in an attempt to enhance the efficacy, benefit from the synergism between the drugs as well as to minimize the development of multi-drug resistance. The main challenge point is the early detection and management of any developed adverse effect.

Cubosomes are bicontinuous cubic phase nanoparticles with a size range from 10-500 nm. They offer various advantages with some limitations at the production level, e.g., cubosomes have the feature to encapsulate a large amount of the drug due to its large internal area owing to cuboidal shape thus has a larger area but limited in large scale production due to its high viscosity which is associated with the problem in homogenization. This nanoparticulate formulation is compatible for administration by various routes like oral, transdermal, topical, buccal, etc. The drug release mechanism from cubosomes was reported to be dependent on the partition coefficient and diffusion process. Compared with liposomes, cubosomes show many differences in various aspects like shape, size, ingredients, and mode of action. The main ingredients for the preparation of cubosomes include lipids, stabilizer, aqueous phases, and therapeutic agents. Several methods have been reported for cubosomes, including the top-down method, the bottom-up method, and the adopted coarse method. For the optimization of cubosomes, the key factors to be considered, which will affect the cubosomes characteristics include; the concentration of lipid, temperature, and pH. At present, many research groups are exploring the potential of cubosomes as biosensors and nanocarriers. Based on the latest reports and research, this review illuminates the structure of the Cubosomes, mechanism of the drug release, different methods of preparation with factors affecting the cubosomes, application of cubosomes in different sectors, differences from the liposomes, and advantages.

There remains a critical need to develop new technologies and materials that can meet the demands of treating large bone defects. The advancement of 3-dimensional (3D) printing technologies has allowed the creation of personalized and customized bone grafts, with specific control in both macro- and micro-architecture, and desired mechanical properties. Nevertheless, the biomaterials used for the production of these bone grafts often possess poor biological properties. The incorporation of growth factors (GFs), which are the natural orchestrators of the physiological healing process, into 3D printed bone grafts, represents a promising strategy to achieve the bioactivity required to enhance bone regeneration. In this review, the possible strategies used to incorporate GFs to 3D printed constructs are presented with a specific focus on bone regeneration. In particular, the strengths and limitations of different methods, such as physical and chemical cross-linking, which are currently used to incorporate GFs to the engineered constructs are critically reviewed. Different strategies used to present one or more GFs to achieve simultaneous angiogenesis and vasculogenesis for enhanced bone regeneration are also covered in this review. In addition, the possibility of combining several manufacturing approaches to fabricate hybrid constructs, which better mimic the complexity of biological niches, is presented. Finally, the clinical relevance of these approaches and the future steps that should be taken are discussed.

Breast cancer (BC) is considered as one the most prevalent cancers worldwide. Due to its high resistance to chemotherapy and high probability of metastasis, BC is one of the leading causes of cancer-related deaths. The controlled release of chemotherapy drugs to the precise site of the tumor tissue will increase the therapeutic efficacy and decrease side effects of systemic administration. Among various drug delivery systems, natural polymers-based drug carriers have gained significant attention for cancer therapy. Chitosan, a natural polymer obtained by de-acetylation of chitin, holds huge potential for drug delivery applications because chitosan is non-toxic, non-immunogenic, biocompatible, chemically modifiable, and can be processed to form various formulations. In the current review, we will discuss the prospects and challenges of chitosan-based drug delivery systems in treating BC.

Introduction: Today, the development of multifunctional nanoplatforms is more seriously considered in the field of cancer theranostics.Areas covered: In this respect, nanoparticles provide several advantages over the routine, conventional diagnostic methods, and treatments. Due to the expedient properties of iron oxide nanoparticles, such as being readily modified, great payload potential, intrinsic magnetic qualification, considerable biocompatibility, and overwhelming response to targeting strategies, these nanoparticles can be considered good candidates for application as diagnostic contrast agents and drug/gene delivery vehicles, while also being incorporated into hyperthermia-based approaches. Interestingly, these agents are detectable with routine imaging modalities such as magnetic resonance imaging.Expert opinion: Therefore, combining the traditional diagnostics and therapies with nanotechnological approaches may leave a positive impact on the survival rate of patients with cancer. This review summarizes the application of magnetic iron oxide nanoparticles in both in vitro and in vivo models of brain tumors.

Diabetes mellitus (DM) is a chronic metabolic disease associated with long-term multisystem complications, among which nonhealing diabetic foot ulcers (DFUs) are recognized as major cause of morbidity and mortality. Treating DFUs with surgical procedures such as synthetic or biological skin grafts or skin substitutes has several limitations, where none of the currently available skin substitutes is ideal.

OVID/Medline and PubMed databases were searched using the Medical Subject Heading (MeSH) or Title/Abstract words ("diabetic foot ulcers", "skin substitutes", and "nanofibers"), to identify published research studies on DFUs and nanofibers.

Electrospinning nanotechnology is being used in the biomedical field to produce polymeric nanofibers impregnated with drugs for wound healing, burns and diabetic ulcers. Those nanofibers also enable seeding of cells into them and culturing them in vitro to synthesize tissue-like structures. Knowing the advantages of generating patient-specific induced pluripotent stem cells (iPSCs) and organoids in three-dimension (3D), including skin organoids, it is worth mingling these technologies to develop tissue-engineered biological skin substitutes.

Nanofiber-skin substitutes hold promise for treatment of patients suffering from DFUs and inspire novel strategies that could be applied to other organ systems as well, introducing a new era of "regenerative and personalized medicine".

Selenium nanoparticles (SeNPs) have advantages over other nanomaterials because of the promising role of selenium in the stabilization of the immune system and activation of the defense response. The use of SeNPs and their supplements not only have pharmacological significance but also boost and prepare the body's immune system to fight the pathogens. This review summarizes the recent progress in the biogenesis of plant-based SeNPs by using various plant species and the role of secondary metabolites on their biocompatible functioning. Phyto-synthesis of SeNPs results in the synthesis of nanomaterials of various, size, shape and biochemical nature and has advantages over other routine physical and chemical methods because of their biocompatibility, eco-friendly nature and in vivo actions. Unfortunately, the plant-based SeNPs failed to attain considerable attention in the pharmaceutical industry. However, a few studies were performed to explore the therapeutic potential of the SeNPs against various cancer cells, microbial pathogens, viral infections, hepatoprotective actions, diabetic management, and antioxidant approaches. Further, some of the selenium-based drug delivery systems are developed by engineering the SeNPs with the functional ligands to deliver drugs to the targeted sites. This review also provides up-to-date information on the mechanistic actions that the SeNPs adopt to achieve their designated tasks as it may help to develop precision medicine with customized treatment and healthcare for the ailing population.

The musculoskeletal system works at a very advanced level of synchrony, where all the physiological movements of the body are systematically performed through well-organized actions of bone in conjunction with all the other musculoskeletal soft tissues, such as ligaments, tendons, muscles, and cartilage through tissue-tissue interfaces. Interfaces are structurally and compositionally complex, consisting of gradients of extracellular matrix components, cell phenotypes as well as biochemical compositions and are important in mediating load transfer between the distinct orthopedic tissues during body movement. When an injury occurs at interface, it must be re-established to restore its function and stability. Due to the structural and compositional complexity found in interfaces, it is anticipated that they presuppose a concomitant increase in the complexity of the associated regenerative engineering approaches and scaffold designs to achieve successful interface regeneration and seamless integration of the engineered orthopedic tissues. Herein, we discuss the various bioinspired scaffold designs utilized to regenerate orthopedic tissue interfaces. First, we start with discussing the structure-function relationship at the interface. We then discuss the current understanding of the mechanism underlying interface regeneration, followed by discussing the current treatment available in the clinic to treat interface injuries. Lastly, we comprehensively discuss the state-of-the-art scaffold designs utilized to regenerate orthopedic tissue interfaces.

Spinal cord injury (SCI) is a devastating health condition that may lead to permanent disabilities and death. Understanding the pathophysiological perspectives of traumatic SCI is essential to define mechanisms that can help in designing recovery strategies. Since central nervous system tissues are notorious for their deficient ability to heal, efforts have been made to identify solutions to aid in restoration of the spinal cord tissues and thus its function. The two main approaches proposed to address this issue are neuroprotection and neuro-regeneration. Neuroprotection involves administering drugs to restore the injured microenvironment to normal after SCI. As for the neuro-regeneration approach, it focuses on axonal sprouting for functional recovery of the injured neural tissues and damaged axons. Despite the progress made in the field, neural regeneration treatment after SCI is still unsatisfactory owing to the disorganized way of axonal growth and extension. Nanomedicine and tissue engineering are considered promising therapeutic approaches that enhance axonal growth and directionality through implanting or injecting of the biomaterial scaffolds. One of these recent approaches is nanofibrous scaffolds that are used to provide physical support to maintain directional axonal growth in the lesion site. Furthermore, these preferable tissue-engineered substrates can afford axonal regeneration by mimicking the extracellular matrix of the neural tissues in terms of biological, chemical, and architectural characteristics. In this review, we discuss the regenerative approach using nanofibrous scaffolds with a focus on their fabrication methods and their properties that define their functionality performed to heal the neural tissue efficiently.

Three-dimensional (3D) printing application is a promising method for bone tissue engineering. For enhanced bone tissue regeneration, it is essential to have printable composite materials with appealing properties such as construct porous, mechanical strength, thermal properties, controlled degradation rates, and the presence of bioactive materials. In this study, polycaprolactone (PCL), gelatin (GEL), bacterial cellulose (BC), and different hydroxyapatite (HA) concentrations were used to fabricate a novel PCL/GEL/BC/HA composite scaffold using 3D printing method for bone tissue engineering applications. Pore structure, mechanical, thermal, and chemical analyses were evaluated. 3D scaffolds with an ideal pore size (~300 µm) for use in bone tissue engineering were generated. The addition of both bacterial cellulose (BC) and hydroxyapatite (HA) into PCL/GEL scaffold increased cell proliferation and attachment. PCL/GEL/BC/HA composite scaffolds provide a potential for bone tissue engineering applications.

Human meniscus is a fibrocartilaginous structure that is crucial for an adequate performance of the human knee joint. Degeneration of the meniscus is often followed by partial or total meniscectomy, which enhances the risk of developing knee osteoarthritis. The lack of a satisfactory treatment for this condition has triggered a major interest in drug delivery (DD) and tissue engineering (TE) strategies intended to restore a bioactive and fully functional meniscal tissue. The aim of this review is to critically discuss the most relevant studies on spatiotemporal DD and TE, aiming for a multizonal meniscal reconstruction. Indeed, the development of meniscal tissue implants should involve a provision for adequate active molecules and scaffold features that take into account the anisotropic ultrastructure of human meniscus. This zonal differentiation is reflected in the meniscus biochemical composition, collagen fiber arrangement, and cell distribution. In this sense, it is expected that a proper combination of advanced DD and zonal TE strategies will play a key role in the future trends in meniscus regeneration. Impact statement Meniscus degeneration is one of the main causes of knee pain, inflammation, and reduced mobility. Currently used suturing procedures and meniscectomy are far from being ideal solutions to the loss of meniscal function. Therefore, drug delivery (DD) and tissue engineering (TE) strategies are currently under investigation. DD systems aim at an in situ controlled release of growth factors, whereas TE strategies aim at mimicking the anisotropy of native meniscus. The goal of this review is to discuss these two main approaches, as well as synergies between them that are expected to lead to a real breakthrough in the field.

Autoimmune diseases affect 10% of the world's population, and 1 in 200 people worldwide suffer from either multiple sclerosis (MS) or type 1 diabetes (T1D). While the targeted organ systems are different, MS and T1D share similarities in terms of autoreactive immune cells playing a critical role in pathogenesis. Both diseases can be managed only symptomatically without curative remission, and treatment options are limited and non-specific. Most current therapies cause some degree of systemic immune suppression, leaving the patients susceptible to opportunistic infections and other complications. Thus, there is considerable interest in the development of immunotherapies not associated with generalized immune suppression for these diseases. This review presents current and preclinical strategies for MS and T1D treatment, emphasizing those aimed to modulate the immune response, including the most recent strategies for tolerance induction. A central focus is on the emerging approaches using nano- and microparticle platforms, their evolution as immunotherapeutic carriers, including those incorporating specific antigens to induce tolerance and reduce unwanted generalized immune suppression.

Physicochemical parameters such as temperature, pH, the concentration of the AgNO₃ and ratio of reactants act synergistically to influence the reaction kinetics, molecular mechanics, enzymatic catalysis and protein conformations that aid to affect the size, shape and biochemical corona of nanoparticles. The present study was performed to investigate the influence of reaction parameters on the bio-fabrication of silver nanoparticles (AgNPs) by using Mentha arvensis and to determine their potential to control the proliferation of colon cancer cells'.

Plant-mediated method was used for the bio-fabrication and stabilization of AgNPs. Reaction parameters were arranged, and surface plasmon resonance (SPR) bands of AgNPs were collected by using a UV-Visible spectrophotometer. NPs were characterized structurally and optically by using SEM, AFM, EDX and DLS techniques. AgNPs and plant aqueous extract were tested against HCT116 colon cancer cells by using SRB assay, Annexin V assay and cell cycle analysis.

Spectrophotometric comparison of various reaction conditions manifested that 5 mM of AgNO₃, 60 °C in an acidic pH and a mixing ratio of 1:9 of plant extract and AgNO₃, respectively, are the optimized conditions for AgNP synthesis. Structural evaluation by SEM, AFM and particle size analysis confirmed that the NPs are <100 nm and are anisotropic, spherical, triangular and moderately dispersed in the colloidal mixture. SRB assay expressed biomass-stabilized AgNPs as effective cytotoxic particles against HCT116 colon cancer cells, and the IC₅₀ was measured at 1.7 µg/mL. Annexin V apoptosis assay further confirmed that the AgNPs induce apoptosis in a dose-dependent manner. Experimental evidence manifested that the AgNPs arrest cell cycle and expressed entrapment of a greater number of cells in the Sub-G1 phase, further verifying the anticancer abilities of AgNPs.

These findings explain the synergistic effects of physicochemical parameters to optimize the phytosynthesis of biocompatible AgNPs to overcome the limitations of conventional chemotherapeutic treatments of colon cancer cells.

The use of bone scaffolds to replace injured or diseased bone has many advantages over the currently used autologous and allogeneic options in clinical practice. This systematic review evaluates the current evidence for non-cellular scaffolds containing bioactive glass on osteogenesis and angiogenesis in animal bone defect models. Studies that reported results of osteogenesis via micro-CT and results of angiogenesis via Microfil perfusion or immunohistochemistry were included in the review. A literature search of PubMed, EMBASE and Scopus was carried out in November 2019 from which nine studies met the inclusion and exclusion criteria. Despite the significant heterogeneity in the composition of the scaffolds used in each study, it could be concluded that scaffolds containing bioactive glass improve bone regeneration in these models, both by osteogenic and angiogenic measures. Incorporation of additional elements into the glass network, using additives, and using biochemical factors generally had a beneficial effect. Comparing the different compositions of non-cellular bioactive glass containing scaffolds is however difficult due to the heterogeneity in bioactive glass compositions, fabrication methods and biochemical additives used.

The correlation between erosion and drug (lidocaine and 6-mercaptopurine, 6-MP) release from amorphous poly(thioether anhydrides), which are synthesized using radical-mediated thiol-ene polymerization, is reported. Cytotoxicity studies of the polymer toward human fibroblast human dermal fibroblasts adult, melanoma A-375, and breast cancer MCF-7 cells are conducted, and drug efficacy of a cancer and autoimmune disease drug (6-MP) when released from the poly(thioether anhydrides) is examined against two cancerous cell types (A-375 and MCF-7). Erosion and drug release studies reveal that lidocaine release is governed by network erosion whereas 6-MP is released by a combination of erosion and diffusion. The cytotoxicity studies show that all three cell types demonstrate high viability, thus cytocompatibility, to poly(thioether anhydrides). Toxicity to the material is dose dependent and comparable to other polyanhydride systems. The 6-MP cancer drug is shown to remain bioactive after encapsulation in the poly(thioether anhydride) matrix and the polymer does not appear to modify the efficacy of the drug.