Management of Brain Cancer and Neurodegenerative Disorders with Polymer-Based Nanoparticles as a Biocompatible Platform.

The blood-brain barrier (BBB) serves as a protective barrier for the central nervous system (CNS) against drugs that enter the bloodstream. The BBB is a key clinical barrier in the treatment of CNS illnesses because it restricts drug entry into the brain. To bypass this barrier and release relevant drugs into the brain matrix, nanotechnology-based delivery systems have been developed. Given the unstable nature of NPs, an appropriate amount of a biocompatible polymer coating on NPs is thought to have a key role in reducing cellular cytotoxicity while also boosting stability. Human serum albumin (HSA), poly (lactic-co-glycolic acid) (PLGA), Polylactide (PLA), poly (alkyl cyanoacrylate) (PACA), gelatin, and chitosan are only a few of the significant polymers mentioned. In this review article, we categorized polymer-coated nanoparticles from basic to complex drug delivery systems and discussed their application as novel drug carriers to the brain.

Clickable Polysaccharides for Biomedical Applications: A Comprehensive Review.

Recent advances in materials science and engineering highlight the importance of designing sophisticated biomaterials with well-defined architectures and tunable properties for emerging biomedical applications. Click chemistry, a powerful method allowing specific and controllable bioorthogonal reactions, has revolutionized our ability to make complex molecular structures with a high level of specificity, selectivity, and yield under mild conditions. These features combined with minimal byproduct formation have enabled the design of a wide range of macromolecular architectures from quick and versatile click reactions. Furthermore, copper-free click chemistry has resulted in a change of paradigm, allowing researchers to perform highly selective chemical reactions in biological environments to further understand the structure and function of cells. In living systems, introducing clickable groups into biomolecules such as polysaccharides (PSA) has been explored as a general approach to conduct medicinal chemistry and potentially help solve healthcare needs. De novo biosynthetic pathways for chemical synthesis have also been exploited and optimized to perform PSA-based bioconjugation inside living cells without interfering with their native processes or functions. This strategy obviates the need for laborious and costly chemical reactions which normally require extensive and time-consuming purification steps. Using these approaches, various PSA-based macromolecules have been manufactured as building blocks for the design of novel biomaterials. Clickable PSA provides a powerful and versatile toolbox for biomaterials scientists and will increasingly play a crucial role in the biomedical field. Specifically, bioclick reactions with PSA have been leveraged for the design of advanced drug delivery systems and minimally invasive injectable hydrogels. In this review article, we have outlined the key aspects and breadth of PSA-derived bioclick reactions as a powerful and versatile toolbox to design advanced polymeric biomaterials for biomedical applications such as molecular imaging, drug delivery, and tissue engineering. Additionally, we have also discussed the past achievements, present developments, and recent trends of clickable PSA-based biomaterials such as 3D printing, as well as their challenges, clinical translatability, and future perspectives.

Advanced bioengineering of female germ cells to preserve fertility.

Oogenesis and folliculogenesis are considered as complex and species-specific cellular differentiation processes, which depend on the in vivo ovarian follicular environment and endocrine cues. Considerable efforts have been devoted to driving the differentiation of female primordial germ cells toward mature oocytes outside of the body. The recent experimental attempts have laid stress on offering a suitable microenvironment to assist the in vitro folliculogenesis and oogenesis. Despite developing a variety of bioengineering techniques and generating functional mature gametes through in vitro oogenesis in earlier studies, we still lack knowledge of appropriate microenvironment conditions for building biomimetic culture systems for female fertility preservation. Therefore, this review paper can provide a source for a large body of scientists developing cutting-edge in vitro culture systems for female germ cells or setting up the next generation of reproductive medicine as feasible options for female infertility treatment. The focal point of this review outlines advanced bioengineering technologies such as 3D biofabricated hydrogels/scaffolds and microfluidic systems utilized with female germlines for fertility preservation through in vitro folliculogenesis and oogenesis.

Advanced Delivery Systems Based on Lysine or Lysine Polymers.

Polylysine and materials that integrate lysine form promising drug delivery platforms. As a cationic macromolecule, a polylysine polymer electrostatically interacts with cells and is efficiently internalized, thereby enabling intracellular delivery. Although polylysine is intrinsically pH-responsive, the conjugation with different functional groups imparts smart, stimuli-responsive traits by adding pH-, temperature-, hypoxia-, redox-, and enzyme-responsive features for enhanced delivery of therapeutic agents. Because of such characteristics, polylysine has been used to deliver various cargos such as small-molecule drugs, genes, proteins, and imaging agents. Furthermore, modifying contrast agents with polylysine has been shown to improve performance, including increasing cellular uptake and stability. In this review, the use of lysine residues, peptides, and polymers in various drug delivery systems has been discussed comprehensively to provide insight into the design and robust manufacturing of lysine-based delivery platforms.

Biodegradable zwitterionic poly(carboxybetaine) microgel for sustained delivery of antibodies with extended stability and preserved function.

Many recent innovative treatments are based on monoclonal antibodies (mAbs) and other protein therapies. Nevertheless, sustained subcutaneous, oral or pulmonary delivery of such therapeutics is limited by the poor stability, short half-life, and non-specific interactions between the antibody (Ab) and delivery vehicle. Protein stabilizers (osmolytes) such as carboxybetaine can prevent non-specific interactions within proteins. In this work, a biodegradable zwitterionic poly(carboxybetaine), pCB, based microgel covalently crosslinked with tetra(ethylene glycol) diacrylate (TTEGDA) was synthesized for Ab encapsulation. The resulting microgels were characterized via FTIR, diffusion NMR, small-angle neutron scattering (SANS), and cell culture studies. The microgels were found to contain up to 97.5% water content and showed excellent degradability that can be tuned with crosslinking density. Cell compatibility of the microgel was studied by assessing the toxicity and immunogenicity in vitro. Cells exposed to microgel showed complete viability and no pro-inflammatory secretion of interleukin 6 (IL6) or tumor necrosis factor-alpha (TNFα). Microgel was loaded with Immunoglobulin G (as a model Ab), using a post-fabrication loading technique, and Ab sustained release from microgels of varying crosslinking densities was studied. The released Abs (especially from the high crosslinked microgels) proved to be completely active and able to bind with Ab receptors. This study opens a new horizon for scientists to use such a platform for local delivery of Abs to the desired target with minimized non-specific interactions.

Development of a multifunctional system based on CoFe2O4@polyacrylic acid NPs conjugated to folic acid and loaded with doxorubicin for cancer theranostics.

In this work, a multifunctional theranostic nanocomposite based on CoFe2O4@polyacrylic acid (PAA)-Folic Acid (FA) Doxorubicin (Dox)loadNPs was designed for the multifunctional cancer treatment. Several techniques such as TEM, DLS,ζ-potential, vibrating sample magnetometer, XRD, and UV-Vis spectrophotometer were applied for investigating physicochemical properties of the nanosystem. The percentage of the loaded drug, loading efficiency,in vitrorelease (pH 5.4 and 7.4),invitroMRI measurements, and MTT assay (4T1 and 9A9 cell lines) were evaluated. Results showed that the percentage of loaded drug and loading efficiency was 53.33 ± 3.5 and 80.00 ± 5.3%, respectively, showing the system's high ability for Dox encapsulation. Release study showed that Dox loaded in the CoFe2O4@PAA-FA(Dox)loadNPs released faster at pH 5.4 than pH 7.4.In vitro, MRI measurements confirmed that CoFe2O4@PAA NPs could be used as a contrast agent in MRI measurements withr2 = 18.2 mM-1s-1. MTT assay demonstrated the biocompatibility of NPs, also showed a more efficient therapeutic effect for CoFe2O4@PAA-FA(Dox)loadNPs than free Dox and CoFe2O4@PAA(Dox)loadNPs.

Bilayer Scaffolds for Interface Tissue Engineering and Regenerative Medicine: A Systematic Reviews.

PURPOSE: This systematic review focus on the application of bilayer scaffolds as an engaging structure for the engineering of multilayered tissues, including vascular and osteochondral tissues, skin, nerve, and urinary bladder. This article provides a concise literature review of different types of bilayer scaffolds to understand their efficacy in targeted tissue engineering. METHODS: To this aim, electronic search in the English language was performed in PMC, NBCI, and PubMed from April 2008 to December 2019 based on the PRISMA guidelines. Animal studies, including the "bilayer scaffold" and at least one of the following items were examined: osteochondral tissue, bone, skin, neural tissue, urinary bladder, vascular system. The articles which didn't include "tissue engineering" and just in vitro studies were excluded. RESULTS: Totally, 600 articles were evaluated; related articles were 145, and 35 full-text English articles met all the criteria. Fifteen articles in soft tissue engineering and twenty items in hard tissue engineering were the results of this exploration. Based on selected papers, it was revealed that the bilayer scaffolds were used in the regeneration of the multilayered tissues. The highest multilayered tissue regeneration has been achieved when bilayer scaffolds were used with mesenchymal stem cells and differentiation medium before implanting. Among the studies being reported in this review, bone marrow mesenchymal stem cells are the most studied mesenchymal stem cells. Among different kinds of multilayer tissue, the bilayer scaffold has been most used in osteochondral tissue engineering in which collagen and PLGA have been the most frequently used biomaterials. After osteochondral tissue engineering, bilayer scaffolds were widely used in skin tissue engineering. CONCLUSION: The current review aimed to manifest the researcher and surgeons to use a more sophisticated bilayer scaffold in combinations of appropriate stem cells, and different can improve multilayer tissue regeneration. This systematic review can pave a way to design a suitable bilayer scaffold for a specific target tissue and conjunction with proper stem cells.

Engineering the niche for hair regeneration - A critical review.

Recent progress in hair follicle regeneration and alopecia treatment necessitates revisiting the concepts and approaches. In this sense, there is a need for shedding light on the clinical and surgical therapies benefitting from nanobiomedicine. From this perspective, this review attempts to recognize requirements upon which new hair therapies are grounded; to underline shortcomings and opportunities associated with recent advanced strategies for hair regeneration; and most critically to look over hair regeneration from nanomaterials and pluripotent stem cell standpoint. It is noteworthy that nanotechnology is able to illuminate a novel path for reprogramming cells and controlled differentiation to achieve the desired performance. Undoubtedly, this strategy needs further advancement and a lot of critical questions have yet to be answered. Herein, we introduce the salient features, the hurdles that must be overcome, the hopes, and practical constraints to engineer stem cell niches for hair follicle regeneration.

Tailor-Made Polysaccharides for Biomedical Applications.

Polysaccharides (PSAs) are carbohydrate-based macromolecules widely used in the biomedical field, either in their pure form or in blends/nanocomposites with other materials. The relationship between structure, properties, and functions has inspired scientists to design multifunctional PSAs for various biomedical applications by incorporating unique molecular structures and targeted bulk properties. Multiple strategies, such as conjugation, grafting, cross-linking, and functionalization, have been explored to control their mechanical properties, electrical conductivity, hydrophilicity, degradability, rheological features, and stimuli-responsiveness. For instance, custom-made PSAs are known for their worldwide biomedical applications in tissue engineering, drug/gene delivery, and regenerative medicine. Furthermore, the remarkable advancements in supramolecular engineering and chemistry have paved the way for mission-oriented biomaterial synthesis and the fabrication of customized biomaterials. These materials can synergistically combine the benefits of biology and chemistry to tackle important biomedical questions. Herein, we categorize and summarize PSAs based on their synthesis methods, and explore the main strategies used to customize their chemical structures. We then highlight various properties of PSAs using practical examples. Lastly, we thoroughly describe the biomedical applications of tailor-made PSAs, along with their current existing challenges and potential future directions.

Electrically conductive carbon-based (bio)-nanomaterials for cardiac tissue engineering.

A proper self-regenerating capability is lacking in human cardiac tissue which along with the alarming rate of deaths associated with cardiovascular disorders makes tissue engineering critical. Novel approaches are now being investigated in order to speedily overcome the challenges in this path. Tissue engineering has been revolutionized by the advent of nanomaterials, and later by the application of carbon-based nanomaterials because of their exceptional variable functionality, conductivity, and mechanical properties. Electrically conductive biomaterials used as cell bearers provide the tissue with an appropriate microenvironment for the specific seeded cells as substrates for the sake of protecting cells in biological media against attacking mechanisms. Nevertheless, their advantages and shortcoming in view of cellular behavior, toxicity, and targeted delivery depend on the tissue in which they are implanted or being used as a scaffold. This review seeks to address, summarize, classify, conceptualize, and discuss the use of carbon-based nanoparticles in cardiac tissue engineering emphasizing their conductivity. We considered electrical conductivity as a key affecting the regeneration of cells. Correspondingly, we reviewed conductive polymers used in tissue engineering and specifically in cardiac repair as key biomaterials with high efficiency. We comprehensively classified and discussed the advantages of using conductive biomaterials in cardiac tissue engineering. An overall review of the open literature on electroactive substrates including carbon-based biomaterials over the last decade was provided, tabulated, and thoroughly discussed. The most commonly used conductive substrates comprising graphene, graphene oxide, carbon nanotubes, and carbon nanofibers in cardiac repair were studied.

Preparation and characterization of TiO2-coated polymerization of methyl methacrylate (PMMA) for biomedical applications: In vitro study.

Low surface energy and hydrophobicity of polymethyl methactylate (PMMA) are the main disadvantages of this biomaterial. The aim of this study was to investigate the effects of a new coating process on the surface characteristics and properties of PMMA. A combination of temperature and pressure was used for deposition of titanium dioxide (TiO2) on the surface of PMMA. The PMMA coated with TiO2 thin films and prepared by sputtering and non-coated PMMA were considered as control groups. The surface wettability, functional group, and roughness were determined by contact angle measurement, Fourier transform Infrared spectroscopy (FTIR), and 3D laser scanning digital microscopy, respectively. The flexural strength of coated and non-coated samples was measured using three-point bending test. The cell proliferation, attachment, and viability were determined using 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide, live and dead assay, scanning electron microscope (SEM), and DAPI (4',6-diamidino-2-phenylindole) staining. The antifungal activity of TiO2 was also determined by examining the biofilm attachment of Candida albicans. The obtained results showed that TiO2 was successfully coated on PMMA. The contact angle measurement shows a significant increase of hydrophilicity in TiO2-coated PMMA. FTIR and roughness analysis revealed no loss of TiO2 from coated specimens following sonication. The cell viability after 7 days culturing on TiO2-coated specimens was more than the cell viability on the control groups. SEM images and DAPI staining showed that the total number of the cells increased after 7 days of seeding on TiO2-coated group, whereas it decreased gradually in both control groups. C. albicans attachment also decreased by 63% to 77% on the coated PMMA surface. Overall, this research suggested a new way for developing surface energy of PMMAs for biomedical applications.

Polydopamine Biomaterials for Skin Regeneration.

Designing biomaterials capable of biomimicking wound healing and skin regeneration has been receiving increasing attention recently. Some biopolymers behave similarly to the extracellular matrix (ECM), supporting biointerfacial adhesion and intrinsic cellular interactions. Polydopamine (PDA) is a natural bioadhesive and bioactive polymer that endows high chemical versatility, making it an exciting candidate for a wide range of biomedical applications. Moreover, biomaterials based on PDA and its derivatives have near-infrared (NIR) absorption, excellent biocompatibility, intrinsic antioxidative activity, antibacterial activity, and cell affinity. PDA can regulate cell behavior by controlling signal transduction pathways. It governs the focal adhesion behavior of cells at the biomaterials interface. These features make melanin-like PDA a fascinating biomaterial for wound healing and skin regeneration. This paper overviews PDA-based biomaterials' synthesis, properties, and interactions with biological entities. Furthermore, the utilization of PDA nano- and microstructures as a constituent of wound-dressing formulations is highlighted.

Polyacrylic Acid Nanoplatforms: Antimicrobial, Tissue Engineering, and Cancer Theranostic Applications.

Polyacrylic acid (PAA) is a non-toxic, biocompatible, and biodegradable polymer that gained lots of interest in recent years. PAA nano-derivatives can be obtained by chemical modification of carboxyl groups with superior chemical properties in comparison to unmodified PAA. For example, nano-particles produced from PAA derivatives can be used to deliver drugs due to their stability and biocompatibility. PAA and its nanoconjugates could also be regarded as stimuli-responsive platforms that make them ideal for drug delivery and antimicrobial applications. These properties make PAA a good candidate for conventional and novel drug carrier systems. Here, we started with synthesis approaches, structure characteristics, and other architectures of PAA nanoplatforms. Then, different conjugations of PAA/nanostructures and their potential in various fields of nanomedicine such as antimicrobial, anticancer, imaging, biosensor, and tissue engineering were discussed. Finally, biocompatibility and challenges of PAA nanoplatforms were highlighted. This review will provide fundamental knowledge and current information connected to the PAA nanoplatforms and their applications in biological fields for a broad audience of researchers, engineers, and newcomers. In this light, PAA nanoplatforms could have great potential for the research and development of new nano vaccines and nano drugs in the future.

Green products from herbal medicine wastes by subcritical water treatment.

Herbal medicine wastes (HMWs) are byproducts of medicine factories, which are mainly landfilled for their environmental problems. Only bearing in mind the contamination and concerns caused by the COVID-19 pandemic and environmental emissions, the worth of herbal medicine wastes management and conversion to green products can be understood. In this work, subcritical water treatment was carried out batch-wise in a stainless tube reactor in the pressure range of 0.792-30.0 MPa, varying the temperature (127-327 °C) and time (1-60 min) of extraction. This resulted in new and green material sources, including organic acids, amino acids, and sugars. Amazingly, at very low extraction times (below 5 min) and high temperatures (above 277 °C), about 99% of HMWs were efficaciously converted to clean products by subcritical hydrothermal treatment. The results of hydrothermal extraction after 5 min indicated that at low temperatures (127-227 °C), the total organic carbon in the aqueous phase increased as the residual solid phase decreased, reaching a peak around 220 °C. Acetone soluble extracts or fat phase appeared above 227 °C and reached a maximum yield of 21% at 357 °C. Aspartic acid, threonine, and glycine were the primary amino acids; glycolic acid, formic acid, lactic acid, and acetic acid were obtained as the main organic acids, glucose, fructose, and cellobiose were substantial sugars produced from the aqueous phase after 5 min of hydrothermal subcritical hydrolysis extraction.

Crystalline polysaccharides: A review.

The biodegradability and mechanical properties of polysaccharides are dependent on their architecture (linear or branched) as well as their crystallinity (size of crystals and crystallinity percent). The amount of crystalline zones in the polysaccharide significantly governs their ultimate properties and applications (from packaging to biomedicine). Although synthesis, characterization, and properties of polysaccharides have been the subject of several review papers, the effects of crystallization kinetics and crystalline domains on the properties and application have not been comprehensively addressed. This review places focus on different aspects of crystallization of polysaccharides as well as applications of crystalline polysaccharides. Crystallization of cellulose, chitin, chitosan, and starch, as the main members of this family, were discussed. Then, application of the aforementioned crystalline polysaccharides and nano-polysaccharides as well as their physical and chemical interactions were overviewed. This review attempts to provide a complete picture of crystallization-property relationship in polysaccharides.

Human Organs-on-Chips: A Review of the State-of-the-Art, Current Prospects, and Future Challenges.

New emerging technologies, remarkably miniaturized 3D organ models and microfluidics, enable simulation of the real in vitro microenvironment ex vivo more closely. There are many fascinating features of innovative organ-on-a-chip (OOC) technology, including the possibility of integrating semipermeable and/or stretchable membranes, creating continuous perfusion of fluids into microchannels and chambers (while maintaining laminar flow regime), embedding microdevices like microsensors, microstimulators, micro heaters, or different cell lines, along with other 3D cell culture technologies. OOC systems are designed to imitate the structure and function of human organs, ranging from breathing lungs to beating hearts. This technology is expected to be able to revolutionize cell biology studies, personalized precision medicine, drug development process, and cancer diagnosis/treatment. OOC systems can significantly reduce the cost associated with tedious drug development processes and the risk of adverse drug reactions in the body, which makes drug screening more effective. The review mainly focus on presenting an overview of the several previously developed OOC systems accompanied by subjects relevant to pharmacy-, cancer-, and placenta-on-a-chip. The challenging issues and opportunities related to these systems are discussed, along with a future perspective for this technology.

Polysaccharide-based electroconductive hydrogels: Structure, properties and biomedical applications.

Architecting an appropriate platform for biomedical applications requires setting a balance between simplicity and complexity. Polysaccharides (PSAs) play essential roles in our life in food resources, structural materials, and energy storage capacitors. Moreover, the diversity and abundance of PSAs have made them an indispensable part of food ingredients and cosmetics. PSA-based hydrogels have been extensively reviewed in biomedical applications. These hydrogels can be designed in different forms to show optimum performance. For instance, electroactive PSA-based hydrogels respond under an electric stimulus. Such performance can be served in stimulus drug release and determining cell fate. This review classifies and discusses the structure, properties, and applications of the most important polysaccharide-based electroactive hydrogels (agarose, alginate, chitosan, cellulose, and dextran) in medicine, focusing on their usage in tissue engineering, flexible electronics, and drug delivery applications.

Green Polymer Nanocomposites for Skin Tissue Engineering.

Fabrication of an appropriate skin scaffold needs to meet several standards related to the mechanical and biological properties. Fully natural/green scaffolds with acceptable biodegradability, biocompatibility, and physiological properties quite often suffer from poor mechanical properties. Therefore, for appropriate skin tissue engineering and to mimic the real functions, we need to use synthetic polymers and/or additives as complements to green polymers. Green nanocomposites (either nanoscale natural macromolecules or biopolymers containing nanoparticles) are a class of scaffolds with acceptable biomedical properties window (drug delivery and cardiac, nerve, bone, cartilage as well as skin tissue engineering), enabling one to achieve the required level of skin regeneration and wound healing. In this review, we have collected, summarized, screened, analyzed, and interpreted the properties of green nanocomposites used in skin tissue engineering and wound dressing. We particularly emphasize the mechanical and biological properties that skin cells need to meet when seeded on the scaffold. In this regard, the latest state of the art studies directed at fabrication of skin tissue and bionanocomposites as well as their mechanistic features are discussed, whereas some unspoken complexities and challenges for future developments are highlighted.

Comparative review of piezoelectric biomaterials approach for bone tissue engineering.

Bone as a minerals' reservoir and rigid tissue of the body generating red and white blood cells supports various organs. Although the self-regeneration property of bone, it cannot regenerate spontaneously in severe damages and still remains as a challenging issue. Tissue engineering offers several techniques for regenerating damaged bones, where various biomaterials are examined to fabricate scaffolds for bone repair. Piezoelectric characteristic plays a crucial role in repairing and regenerating damaged bone by mimicking the bone niche behavior. Piezoelectric biomaterials show significant potential for bone tissue engineering. Herein we try to have a comparative review on piezoelectric and non-piezoelectric biomaterials used in bone tissue engineering, classified them, and discussed their effects on implanted cells and manufacturing techniques. Especially, Polyvinylidene fluoride (PVDF) and its composites are the most practically used piezoelectric biomaterials for bone regeneration. PVDF and its composites have been summarized and discussed to repair damaged bone tissues.

Mussel-inspired biomaterials: From chemistry to clinic.

After several billions of years, nature still makes decisions on its own to identify, develop, and direct the most effective material for phenomena/challenges faced. Likewise, and inspired by the nature, we learned how to take steps in developing new technologies and materials innovations. Wet and strong adhesion by Mytilidae mussels (among which Mytilus edulis-blue mussel and Mytilus californianus-California mussel are the most well-known species) has been an inspiration in developing advanced adhesives for the moist condition. The wet adhesion phenomenon is significant in designing tissue adhesives and surgical sealants. However, a deep understanding of engaged chemical moieties, microenvironmental conditions of secreted proteins, and other contributing mechanisms for outstanding wet adhesion mussels are essential for the optimal design of wet glues. In this review, all aspects of wet adhesion of Mytilidae mussels, as well as different strategies needed for designing and fabricating wet adhesives are discussed from a chemistry point of view. Developed muscle-inspired chemistry is a versatile technique when designing not only wet adhesive, but also, in several more applications, especially in the bioengineering area. The applications of muscle-inspired biomaterials in various medical applications are summarized for future developments in the field.