Regenerative Medicine Group (REMED)

REMED.USERN@gmail.com

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Objective

In this group, we aim to gather the related sciences from all scientific majors. Basic scientists, medical doctors, and engineering experts are invited to develop this field of converging technologies. Molecular scientists, Biologists, Anatomists, Oncologists, Hematologists, and all experts in laboratory sciences, chemical, materials, electrical, and mechanical engineering sciences, are kindly called to join in “REMED” to pursue transcendent human goals. Tissue engineering, stem cells, gene and cell therapy, and their merging are of great importance aim of this group.

Definition

Regenerative medicine holds the promise to restitute the normal function of cells, tissues or organs lost due to disease or damage via replacing or regenerating. An up-ward progressive trend of regenerative medicine acts as a precursor in order to translate promising technologies from the bench top to the clinic.

Group members

Founder

Nima Beheshtizadeh

Managing Director

Nima Beheshtizadeh

Member

Paper

REMED proposed activities:

• Publishing scientific papers (Original, Review) • Publishing Books and Book chapters • Organizing technical & scientific workshops. • Organizing conferences & seminars in regenerative medicine filed • Group participation in international conferences ................................... For getting latest news, please follow us at: ......................................... Telegram channel (https://t.me/Usern_Remed) .............................................................................. WhatsApp Group (https://chat.whatsapp.com/H56YTZeS71c7bjrm4N364m)

Stem Cell Therapy Potency in Personalizing Severe COVID-19 Treatment

A wide range of variations in the clinical symptoms of different patients attributed to genomic differences. Hence, personalized treatments seem to play a critical role in improving these symptoms and even similar conditions. This study focuses on the potential application of personalized medicine in treating severe cases of COVID-19. However, it is theoretical, as any real-world examples of the use of genuinely personalized medicine have not existed yet. Several scientific communities have not accepted the idea of cell-based therapy, but the MSCs and their clinical outcomes have been revealed the safety and potency of this therapeutic approach in several diseases. Promising outcomes have resulted in that clinical studies are going to continue.

A network analysis of angiogenesis/osteogenesis-related growth factors in bone tissue engineering based on in-vitro and in-vivo data: A systems biology approach

The principal purpose of tissue engineering is to stimulate the injured or unhealthy tissues to revive their primary function through the simultaneous use of chemical agents, cells, and biocompatible materials. Still, choosing the appropriate protein as a growth factor (GF) for tissue engineering is vital to fabricate artificial tissues and accelerate the regeneration procedure. In this study, the angiogenesis and osteogenesis-related proteins’ interactions are studied using their related network. Three major biological processes, including osteogenesis, angiogenesis, and angiogenesis regulation, were investigated by creating a protein-protein interaction (PPI) network (45 nodes and 237 edges) of bone regeneration efficient proteins. Furthermore, a gene ontology and a centrality analysis were performed to identify essential proteins within a network. The higher degree in this network leads to higher interactions between proteins and causes a considerable effect. The most highly connected proteins in the PPI network are the most remarkable for their employment. The results of this study showed that three significant proteins including prostaglandin endoperoxide synthase 2 (PTGS2), TEK receptor tyrosine kinase (TEK), and fibroblast growth factor 18 (FGF18) were involved simultaneously in osteogenesis, angiogenesis, and their positive regulatory. Regarding the available literature, the results of this study confirmed that PTGS2 and FGF18 could be used as a GF in bone tissue engineering (BTE) applications to promote angiogenesis and osteogenesis. Nevertheless, TEK was not used in BTE applications until now and should be considered in future works to be examined in-vitro and in-vivo.

Recent advances in regenerative medicine strategies for cancer treatment

Cancer stands as one of the most leading causes of death worldwide, while one of the most significant challenges in treating it is revealing novel alternatives to predict, diagnose, and eradicate tumor cell growth. Although various methods, such as surgery, chemotherapy, and radiation therapy, are used today to treat cancer, its mortality rate is still high due to the numerous shortcomings of each approach. Regenerative medicine field, including tissue engineering, cell therapy, gene therapy, participate in cancer treatment and development of cancer models to improve the understanding of cancer biology. The final intention is to convey fundamental and laboratory research to effective clinical treatments, from the bench to the bedside. Proper interpretation of research attempts helps to lessen the burden of treatment and illness for patients. The purpose of this review is to investigate the role of regenerative medicine in accelerating and improving cancer treatment. This study examines the capabilities of regenerative medicine in providing novel cancer treatments and the effectiveness of these treatments to clarify this path as much as possible and promote advanced future research in this field.

Identification of regeneration-involved growth factors in cartilage engineering procedure promotes its reconstruction

Aim: To fabricate mature cartilage for implantation, developmental biological processes and proteins should be understood and employed. Methods: A systems biology study of all protein-coding genes participating in cartilage regeneration resulted in a network graph with 11 nodes and 28 edges. Gene ontology and centrality analysis were performed based on the degree index. Results: The four most crucial biological processes along with the seven most interactive proteins involved in cartilage regeneration were identified. Some proteins, which are under serious discussion in cartilage developmental and disease processes, are included in regeneration. Conclusions: Findings positively correlate with the literature, supporting the use of the four most impressive proteins as growth factors applicable to cartilage tissue engineering, including COL2A1, SOX9, CTGF, and TGFβ1.

A deep insight into the preparation of ceramic bone scaffolds utilizing robocasting technique

From long ago, orthopedists and physicians are trying to deal with bone diseases and disorders, while today, in the regenerative medicine field, bone scaffolds are being in attendance. Although there were common methods for fabricating bone scaffolds, such as foam casting and gas foaming, additive manufacturing (AM) techniques have been considered for producing bone scaffolds due to some appealing features such as creating a hierarchical structure, regular and controlled porosity, and designing of the complicated structures. AM techniques are divided into three categories, including extrusion-based, powder-based, and vat polymerization (light-based) techniques. Among the AM methods, the robocasting technique as an extrusion-based method is highly regarded for designing high-strength scaffolds for bone tissue regeneration owing to special features, for instance, a low-volume binder and the ability to print all types of ceramic materials as well as metals and polymers. This study discusses the robocasting method, as well as the essential parameters that are involved in 3D printing of the ideal scaffold with this method, such as the material, the structure of the robotic device, the printing parameters, the properties of the ideal paste or ink, the role of binder and its types in robocasting, and the rheological properties required in robocasting method. Also, future prospects and clinical applications of this technique were reviewed.

Improving the self-assembly of bioresponsive nanocarriers by engineering doped nanocarbons: a computational atomistic insight

Here, molecular dynamics (MD) simulations were employed to explore the self-assembly of polymers and docetaxel (DTX) as an anticancer drug in the presence of nitrogen, phosphorous, and boron-nitrogen incorporated graphene and fullerene. The electrostatic potential and the Gibbs free energy of the self-assembled materials were used to optimize the atomic doping percentage of the N- and P-doped formulations at 10% and 50%, respectively. Poly lactic-glycolic acid (PLGA)- polyethylene glycol (PEG)-based polymeric nanoparticles were assembled in the presence of nanocarbons in the common (corresponding to the bulk environment) and interface of organic/aqueous solutions (corresponding to the microfluidic environment). Assessment of the modeling results (e.g., size, hydrophobicity, and energy) indicated that among the nanocarbons, the N-doped graphene nanosheet in the interface method created more stable polymeric nanoparticles (PNPs). Energy analysis demonstrated that doping with nanocarbons increased the electrostatic interaction energy in the self-assembly process. On the other hand, the fullerene-based nanocarbons promoted van der Waals intramolecular interactions in the PNPs. Next, the selected N-doped graphene nanosheet was utilized to prepare nanoparticles and explore the physicochemical properties of the nanosheets in the permeation of the resultant nanoparticles through cell-based lipid bilayer membranes. In agreement with the previous results, the N-graphene assisted PNP in the interface method and was translocated into and through the cell membrane with more stable interactions. In summary, the present MD simulation results demonstrated the success of 2D graphene dopants in the nucleation and growth of PLGA-based nanoparticles for improving anticancer drug delivery to cells, establishing new promising materials and a way to assess their performance that should be further studied.

Regenerative strategies for the consequences of myocardial infarction: Chronological indication and upcoming visions

Heart muscle injury and an elevated troponin level signify myocardial infarction (MI), which may result in defective and uncoordinated segments, reduced cardiac output, and ultimately, death. Physicians apply thrombolytic therapy, coronary artery bypass graft (CABG) surgery, or percutaneous coronary intervention (PCI) to recanalize and restore blood flow to the coronary arteries, albeit they were not convincingly able to solve the heart problems. Thus, researchers aim to introduce novel substitutional therapies for regenerating and functionalizing damaged cardiac tissue based on engineering concepts. Cell-based engineering approaches, utilizing biomaterials, gene, drug, growth factor delivery systems, and tissue engineering are the most leading studies in the field of heart regeneration. Also, understanding the primary cause of MI and thus selecting the most efficient treatment method can be enhanced by preparing microdevices so-called heart-on-a-chip. In this regard, microfluidic approaches can be used as diagnostic platforms or drug screening in cardiac disease treatment. Additionally, bioprinting technique with whole organ 3D printing of human heart with major vessels, cardiomyocytes and endothelial cells can be an ideal goal for cardiac tissue engineering and remarkable achievement in near future. Consequently, this review discusses the different aspects, advancements, and challenges of the mentioned methods with presenting the advantages and disadvantages, chronological indications, and application prospects of various novel therapeutic approaches.

Applying extrusion-based 3D printing technique accelerates fabricating complex biphasic calcium phosphate-based scaffolds for bone tissue regeneration

Background: Tissue engineering (TE) is the main approach for stimulating the body’s mechanisms to regenerate damaged or diseased organs. Bone and cartilage tissues due to high susceptibility to trauma, tumors, and age-related disease exposures are often need for reconstruction. Investigation on the development and applications of the novel biomaterials and methods in bone tissue engineering (BTE) is of great importance to meet emerging today’s life requirements. Aim of review: Biphasic calcium phosphates (BCPs) offer a chemically similar biomaterial to the natural bone, which can significantly promote cell proliferation and differentiation and accelerate bone formation and reconstruction. Recent advancements in the bone scaffold fabrication have led to employing additive manufacturing (AM) methods. Extrusion-based 3D printing, known also as robocasting method, is one of the extensively used AM techniques in BTE applications. This review discusses materials and methods utilized for BCP robocasting. Key scientific concepts of review: Recent advancements and existing challenges in the use of additives for bioink preparation are critically discussed. Commercialization and marketing approach, post-processing steps, clinical applications, in-vitro and in-vivo evaluations beside the biological responses are also reviewed. Finally, possible strategies and opportunities for the use of BCP toward injured bone regeneration are discussed.

Advanced approaches to regenerate spinal cord injury: The development of cell and tissue engineering therapy and combinational treatments

Spinal cord injury (SCI) is a central nervous system (CNS) devastate event that is commonly caused by traumatic or non-traumatic events. The reinnervation of spinal cord axons is hampered through a myriad of devices counting on the damaged myelin, inflammation, glial scar, and defective inhibitory molecules. Unfortunately, an effective treatment to completely repair SCI and improve functional recovery has not been found. In this regard, strategies such as using cells, biomaterials, biomolecules, and drugs have been reported to be effective for SCI recovery. Furthermore, recent advances in combinatorial treatments, which address various aspects of SCI pathophysiology, provide optimistic outcomes for spinal cord regeneration. According to the global importance of SCI, the goal of this article review is to provide an overview of the pathophysiology of SCI, with an emphasis on the latest modes of intervention and current advanced approaches for the treatment of SCI, in conjunction with an assessment of combinatorial approaches in preclinical and clinical trials. So, this article can give scientists and clinicians' clues to help them better understand how to construct preclinical and clinical studies that could lead to a breakthrough in spinal cord regeneration.

Specific Regulatory Motifs Network in SARS-CoV-2-Infected Caco-2 Cell Line, as a Model of Gastrointestinal Infections

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was primarily noted as a respiratory pathogen, but later clinical reports highlighted its extrapulmonary effects particularly on the gastrointestinal (GI) tract. The aim of the current study was the prediction of crucial genes associated with the regulatory network motifs, probably responsible for the SARS-CoV-2 effects on the GI tract. The data were obtained from a published study on the effect of SARS-CoV-2 on the Caco-2 (colon carcinoma) cell line. We used transcription factors-microRNA-gene interaction databases to find the key regulatory molecules, then analyzed the data using the FANMOD software for detection of the crucial regulatory motifs. Cytoscape software was then used to construct and analyze the regulatory network of these motifs and identify their crucial genes. Finally, GEPIA2 (Gene Expression Profiling Interactive Analysis 2) and UALCAN datasets were used to evaluate the possible relationship between crucial genes and colon cancer development. Using bioinformatics tools, we demonstrated one 3edge feed-forward loop motifs and recognized 10 crucial genes in relationship with Caco-2 cell infected by SARS-CoV-2, including SP1, TSC22D2, POU2F1, REST, NFIC, CHD7, E2F1, CEBPA, TCF7L2, and TSC22D1. The box plot analysis indicated the significant overexpression of CEBPA in colon cancer compared to normal colon tissues, while it was in contrast with the results of stage plot. However, the overall survival analysis indicated that high expression of CEBPA has positive effect on colon cancer patient survivability, verifying the results of CEBPA stage plot. We predict that the SARS-CoV-2 GI infections may cause a serious risk in colon cancer patients. However, further experimental studies are required.

Portable hand-held bioprinters promote in situ tissue regeneration

Three-dimensional bioprinting, as a novel technique of fabricating engineered tissues, is positively correlated with the ultimate goal of regenerative medicine, which is the restoration, reconstruction, and repair of lost and/or damaged tissue function. The progressive trend of this technology resulted in developing the portable hand-held bioprinters, which could be used quite easily by surgeons and physicians. With the advent of portable hand-held bioprinters, the obstacles and challenges of utilizing statistical bioprinters could be resolved. This review attempts to discuss the advantages and challenges of portable hand-held bioprinters via in situ tissue regeneration. All the tissues that have been investigated by this approach were reviewed, including skin, cartilage, bone, dental, and skeletal muscle regeneration, while the tissues that could be regenerated via this approach are targeted in the authors' perspective. The design and applications of hand-held bioprinters were discussed widely, and the marketed printers were introduced. It has been prospected that these facilities could ameliorate translating the regenerative medicine science from the bench to the bedside actively.

Artificial Intelligence Deep Exploration of Influential Parameters on Physicochemical Properties of Curcumin-Loaded Electrospun Nanofibers

Artificial intelligence (AI) methods are explosively considered in the design and optimization of drug discovery and delivery systems. Herein, machine learning methods are used for optimizing the production of curcumin (CUR)-loaded nanofibers. The required data are mined through the literature survey and two categories, including material- and machine-based parameters, are detected and studied as effective parameters on the final outcomes. AI results show that high-density polymers have a lower CUR release rate; however, with the increase in polymer density, CUR encapsulation efficiency (EE) increases in many types of polymers. The smallest diameter, highest EE, and highest drug release percentage are obtained at a molecular weight between 100 and 150 kDa and a CUR concentration of 10–15 wt%, with the polymer density in the range of 1.2–1.5 g mL−1. Also, the optimal distance of ≈23 cm, the flow rate of 3.5–4.5 mL h−1, and the voltage at the range of 12.5–15 kV result in the highest release rate, highest EE, and the lowest average diameter for fibers. These findings open up new roads for future design and production of drug-loaded polymeric nanofibers with desirable properties and performances by AI methods.

A study on the anticancer and antimicrobial activity of Curcumin nanodispersion and synthesized ZnO nanoparticles

Curcumin is an essential natural bioactive component with a wide range of biological applications, possessing advantages and disadvantages. The main drawback of Curcumin is its poor bioavailability due to its poor aqueous solubility. In this paper, Curcumin nanodispersion and synthesized ZnO nanoparticles with Curcumin nanodispersion (ZnO NPs) at pH = 7 and 10 were compared to increase bioavailability. This work aimed to investigate the bioavailability measurement, antimicrobial activities, and anticancer features of Curcumin nanodispersion and synthesized ZnO NPs. The SEM images showed that the size of ZnO NPs was nanoscales with 10–100 nm particles. Furthermore, DLS analysis revealed that the average particle size of the prepared Curcumin nanodispersion and synthesized ZnO NPs were 32 and 85 nm, respectively. The results of this investigation exhibit that prepared samples have high antibacterial and antifungal characteristics. Analyzing the cytotoxicity of prepared samples via MTT assay in HT-29 cancer cells and L929 mouse fibroblast cells revealed higher cellular inhibition and better bioavailability of Curcumin nanodispersion, along with ZnO NPs at a pH of 7, compared to pure Curcumin. The viability percentage of HT-29 cancer cells against pure Curcumin, Curcumin nanodispersion, and synthesized ZnO at pH equal to 7 and 10 for 72 h of incubation were 94%, 18%, 14%, and 35%, respectively. However, synthesized ZnO NPs at a pH of approximately 10 exhibited high toxicity on the L929 mouse fibroblast cells. It was concluded that Curcumin nanodispersion possesses antimicrobial and anticancer activities, which could be used in food industry applications.

An In-Silico Study on the Most Effective Growth Factors in Retinal Regeneration Utilizing Tissue Engineering Concepts

Purpose Considering the significance of retinal disorders and the growing need to employ tissue engineering in this field, in-silico studies can be used to establish a cost-effective method. This in-silico study was performed to find the most effective growth factors contributing to retinal tissue engineering. Methods In this study, a regeneration gene database was used. All 21 protein-coding genes participating in retinal regeneration were considered as a protein–protein interaction (PPI) network via the “STRING App” in “Cytoscape 3.7.2” software. The resultant graph possessed 21 nodes as well as 37 edges. Gene ontology (GO) analysis, as well as the centrality analysis, revealed the most effective proteins in retinal regeneration. Results According to the biological processes and the role of each protein in different pathways, selecting the correct one is possible through the information that the network provides. Eye development, detection of the visible light, visual perception, photoreceptor cell differentiation, camera-type eye development, eye morphogenesis, and angiogenesis are the major biological processes in retinal regeneration. Based on the GO analysis, SHH, STAT3, FGFR1, OPN4, ITGAV, RAX, and RPE65 are effective in retinal regeneration via the biological processes. In addition, based on the centrality analysis, four proteins have the greatest influence on retinal regeneration: SHH, IGF1, STAT3, and ASCL1. Conclusion With the intention of applying the most impressive growth factors in retinal engineering, it seems logical to pay attention to SHH, STAT3, and RPE65. Utilizing these proteins can lead to fabricate high efficiency engineered retina via all aforementioned biological processes.

3D printing of complicated GelMA-coated Alginate/Tri-calcium silicate scaffold for accelerated bone regeneration

Polymer-based composite scaffolds are an attractive class of biomaterials due to their suitable physical and mechanical performance as well as appropriate biological properties. When such composites contain osteoinductive ceramic nanopowders, it is possible, in principle, to stimulate the seeded cells to differentiate into osteoblasts. However, reproducibly fabricating and developing an appropriate niche for cells' activities in three-dimensional (3D) scaffolds remains a challenge using conventional fabrication techniques. Additive manufacturing provides a new strategy for the fabrication of complex 3D structures. Here, an extrusion-based 3D printing method was used to fabricate the Alginate (Alg)/Tri-calcium silicate (C3S) bone scaffolds. To improve physical and biological attributes, scaffolds were coated with gelatin methacryloyl (GelMA), a biocompatible viscose hydrogel. Conducting a combination of experimental techniques and molecular dynamics simulations, it is found that the composition ratio of Alg/C3S governs intermolecular interactions among the polymer and ceramic, affecting the product performance. Investigating the effects of various C3S amounts in the bioinks, the 90/10 composition ratio of Alg/C3S is known as the optimum content in developed bioinks. Accordingly, the printability of high-viscosity inks is boosted by improved hierarchical interactions among assemblies, which in turn leads to better nanoscale alignment in extruded macroscopic filaments. Conducting multiple tests on specimens, the GelMA-coated Alg/C3S scaffolds (with a composition ratio of 90/10) were shown to have improved mechanical qualities and cell adhesion, spreading, proliferation, and osteogenic differentiation, compared to the bare scaffolds, making them better candidates for further future research. Overall, the in-silico and in vitro studies of GelMA-coated 3D-printed Alg/C3S scaffolds open new aspects for biomaterials aimed at the regeneration of large- and complicated-bone defects through modifying the extrusion-based 3D-printed constructs.

Recent advances in electrospun protein fibers/nanofibers for the food and biomedical applications

Electrospinning (ES) is one of the most investigated processes for the convenient, adaptive, and scalable manufacturing of nano/micro/macro-fibers. With this technique, virgin and composite fibers may be made in different designs using a wide range of polymers (both natural and synthetic). Electrospun protein fibers (EPF) shave desirable capabilities such as biocompatibility, low toxicity, degradability, and solvolysis. However, issues with the proteins' processibility have limited their widespread utilization. This paper gives an overview of the features of protein-based biomaterials, which are already being employed and has the potential to be exploited for ES. State-of-the-art examples showcasing the usefulness of EPFs in the food and biomedical industries, including tissue engineering, wound dressings, and drug delivery, provided in the applications. The EPFs' future perspective and the challenge they pose are presented at the end. It is believed that protein and biopolymeric nanofibers will soon be manufactured on an industrial scale owing to the limitations of employing synthetic materials, as well as enormous potential of nanofibers in other fields, such as active food packaging, regenerative medicine, drug delivery, cosmetic, and filtration.

Could we use metallic wood for bone tissue engineering applications?

The principal purpose of tissue engineering is to stimulate the injured or unhealthy tissues to revive their primary function through the simultaneous use of chemical agents, cells, and biocompatible materials. One of the most recently used cellular materials is metallic wood, which possesses the strength of titanium as well as the density of natural materials, such as wood and water. Aside from its density, its cellular structure is also efficient, in which some parts are thick and dense, which hold the structure, and others are porous, which supports biological functions. This material has been predicted to be effective in bone tissue engineering in addition to several industrial applications as a result of its essential features, including its cellular structure, outstanding biocompatibility, mechanical performance, nanostructure lattice, high strength, corrosion resistance, and shape memory behavior. Thus, it is predicted that bone grafts made from metallic wood would have an acceptable rate of cell attachment, cell survival, vascularization, and new bone formation. The current review discusses the potential of utilizing metallic wood in bone tissue engineering applications, illustrating its coating and manufacturing capabilities.

Application of nano-radiosensitizers in combination cancer therapy

Radiosensitizers are compounds or nanostructures, which can improve the efficiency of ionizing radiation to kill cells. Radiosensitization increases the susceptibility of cancer cells to radiation-induced killing, while simultaneously reducing the potentially damaging effect on the cellular structure and function of the surrounding healthy tissues. Therefore, radiosensitizers are therapeutic agents used to boost the effectiveness of radiation treatment. The complexity and heterogeneity of cancer, and the multifactorial nature of its pathophysiology has led to many approaches to treatment. The effectiveness of each approach has been proven to some extent, but no definitive treatment to eradicate cancer has been discovered. The current review discusses a broad range of nano-radiosensitizers, summarizing possible combinations of radiosensitizing NPs with several other types of cancer therapy options, focusing on the benefits and drawbacks, challenges, and future prospects.

Enhanced bone tissue regeneration using a 3D‑printed poly(lactic acid)/Ti6Al4V composite scaffold with plasma treatment modification

The mechanical and biological properties of polylactic acid (PLA) need to be further improved in order to be used for bone tissue engineering (BTE). Utilizing a material extrusion technique, three-dimensional (3D) PLA-Ti6Al4V (Ti64) scaffolds with open pores and interconnected channels were successfully fabricated. In spite of the fact that the glass transition temperature of PLA increased with the addition of Ti64, the melting and crystallization temperatures as well as the thermal stability of filaments decreased slightly. However, the addition of 3–6 wt% Ti64 enhanced the mechanical properties of PLA, increasing the ultimate compressive strength and compressive modulus of PLA-3Ti64 to 49.9 MPa and 1.9 GPa, respectively. Additionally, the flowability evaluations revealed that all composite filaments met the print requirements. During the plasma treatment of scaffolds, not only was the root-mean-square (Rq) of PLA (1.8 nm) increased to 60 nm, but also its contact angle (90.4°) significantly decreased to (46.9°). FTIR analysis confirmed the higher hydrophilicity as oxygen-containing groups became more intense. By virtue of the outstanding role of plasma treatment as well as Ti64 addition, a marked improvement was observed in Wharton's jelly mesenchymal stem cell attachment, proliferation (4′,6-diamidino-2-phenylindole staining), and differentiation (Alkaline phosphatase and Alizarin Red S staining). Based on these results, it appears that the fabricated scaffolds have potential applications in BTE.

Engineering of a core-shell polyvinyl alcohol/gelatin fibrous scaffold for dual delivery of Thymus daenensis essential oil and Glycyrrhiza glabra L. extract as an antibacterial and functional wound dressing

Wound healing is an intricate process that can be delayed by the bacterial infection. Extracts or essential oils from medicinal plants have recently shown increased interest given the emergence of antimicrobial resistance to antibiotics. In this study, we evaluated the synergistic effect of thymus essential oil and Licorice extract on wound healing applications. Core-shell nanofibrous scaffolds were fabricated using polyvinyl alcohol (PVA)/Gelatin (Gel)/thymus essential oil as the core (antibacterial agent) and PVA/Gel/licorice extract as the shell. SEM images of the he developed nanocomposite fibers show a monotonic, smooth, and bead-free morphology. The average diameter of PVA/Gel nanofibers was 119 nm and it was observed to increase as the essential oil and extract were added. FTIR technique was used to evaluate the chemical structure of developed nanofiber scaffolds. The core-shell nanocomposite fibers demonstrated promising antibacterial activity against both gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae. Furthermore, the nanocomposite scaffolds promoted proliferation of fibroblasts (L929) and was hemo-compatible in hemolysis and blood clotting assays. Developed nanofibers exhibited effective migration of fibroblasts in in vitro wound healing assays. Therefore, these results substantiated the synergistic effects of licorice extract and thymus essential oil and pose promising potential as materials of choice for wound healing applications.

In-silico engineering of RNA nanoplatforms to promote the diabetic wound healing

One of the most notable required features of wound healing is the enhancement of angiogenesis, which aids in the acceleration of regeneration. Poor angiogenesis during diabetic wound healing is linked to a shortage of pro-angiogenic or an increase in anti-angiogenic factors. As a result, a potential treatment method is to increase angiogenesis promoters and decrease suppressors. Incorporating microRNAs (miRNAs) and small interfering RNAs (siRNAs), two forms of quite small RNA molecules, is one way to make use of RNA interference. Several different types of antagomirs and siRNAs are now in the works to counteract the negative effects of miRNAs. The purpose of this research is to locate novel antagonists for miRNAs and siRNAs that target multiple genes to promote angiogenesis and wound healing in diabetic ulcers. In this context, we used gene ontology analysis by exploring across several datasets. Following data analysis, it was processed using a systems biology approach. The feasibility of incorporating the proposed siRNAs and miRNA antagomirs into polymeric bioresponsive nanocarriers for wound delivery was further investigated by means of a molecular dynamics (MD) simulation study. Among the three nanocarriers tested (Poly (lactic-co-glycolic acid) (PLGA), Polyethylenimine (PEI), and Chitosan (CTS), MD simulations show that the integration of PLGA/hsa-mir- 422a is the most stable (total energy = -1202.62 KJ/mol, Gyration radius = 2.154 nm, and solvent-accessible surface area = 408.416 nm2). With values of -25.437 KJ/mol, 0.047 nm for the Gyration radius, and 204.563 nm2 for the SASA, the integration of the second siRNA/ Chitosan took the last place. The results of the systems biology and MD simulations show that the suggested RNA may be delivered through bioresponsive nanocarriers to speed up wound healing by boosting angiogenesis.

Mesenchymal stromal cells and CAR-T cells in regenerative medicine: The homing procedure and their effective parameters

Mesenchymal stromal cells (MSCs) and chimeric antigen receptor (CAR)-T cells are two core elements in cell therapy procedures. MSCs have significant immunomodulatory effects that alleviate inflammation in the tissue regeneration process, while administration of specific chemokines and adhesive molecules would primarily facilitate CAR-T cell trafficking into solid tumors. Multiple parameters affect cell homing, including the recipient's age, the number of cell passages, proper cell culture, and the delivery method. In addition, several chemokines are involved in the tumor microenvironment, affecting the homing procedure. This review discusses parameters that improve the efficiency of cell homing and significant cell therapy challenges. Emerging comprehensive mechanistic strategies such as non-systemic and systemic homing that revealed a significant role in cell therapy remodeling were also reviewed. Finally, the primary implications for the development of combination therapies that incorporate both MSCs and CAR-T cells for cancer treatment were discussed.

Recent advances on 3D-printed PCL-based composite scaffolds for bone tissue engineering

Population ageing and various diseases have increased the demand for bone grafts in recent decades. Bone tissue engineering (BTE) using a three-dimensional (3D) scaffold helps to create a suitable microenvironment for cell proliferation and regeneration of damaged tissues or organs. The 3D printing technique is a beneficial tool in BTE scaffold fabrication with appropriate features such as spatial control of microarchitecture and scaffold composition, high efficiency, and high precision. Various biomaterials could be used in BTE applications. PCL, as a thermoplastic and linear aliphatic polyester, is one of the most widely used polymers in bone scaffold fabrication. High biocompatibility, low cost, easy processing, non-carcinogenicity, low immunogenicity, and a slow degradation rate make this semi-crystalline polymer suitable for use in load-bearing bones. Combining PCL with other biomaterials, drugs, growth factors, and cells has improved its properties and helped heal bone lesions. The integration of PCL composites with the new 3D printing method has made it a promising approach for the effective treatment of bone injuries. The purpose of this review is give a comprehensive overview of the role of printed PCL composite scaffolds in bone repair and the path ahead to enter the clinic. This study will investigate the types of 3D printing methods for making PCL composites and the optimal compounds for making PCL composites to accelerate bone healing.

Biomaterial-based delivery platforms for transdermal immunotherapy

Nowadays, immunotherapy is one of the most essential treatments for various diseases and a broad spectrum of disorders are assumed to be treated by altering the function of the immune system. For this reason, immunotherapy has attracted a great deal of attention and numerous studies on different approaches for immunotherapies have been investigated, using multiple biomaterials and carriers, from nanoparticles (NPs) to microneedles (MNs). In this review, the immunotherapy strategies, biomaterials, devices, and diseases supposed to be treated by immunotherapeutic strategies are reviewed. Several transdermal therapeutic methods, including semisolids, skin patches, chemical, and physical skin penetration enhancers, are discussed. MNs are the most frequent devices implemented in transdermal immunotherapy of cancers (e.g., melanoma, squamous cell carcinoma, cervical, and breast cancer), infectious (e.g., COVID-19), allergic and autoimmune disorders (e.g., Duchenne’s muscular dystrophy and Pollinosis). The biomaterials used in transdermal immunotherapy vary in shape, size, and sensitivity to external stimuli (e.g., magnetic field, photo, redox, pH, thermal, and even multi-stimuli-responsive) were reported. Correspondingly, vesicle-based NPs, including niosomes, transferosomes, ethosomes, microemulsions, transfersomes, and exosomes, are also discussed. In addition, transdermal immunotherapy using vaccines has been reviewed for Ebola, Neisseria gonorrhoeae, Hepatitis B virus, Influenza virus, respiratory syncytial virus, Hand-foot-and-mouth disease, and Tetanus.

Adult hippocampal neurogenesis (AHN) controls central nervous system and promotes peripheral nervous system regeneration via physical exercise

Physical exercise has beneficial effects on adult hippocampal neurogenesis (AHN) and cognitive processes, including learning. Although it is not known if anaerobic resistance training and high-intensity interval training, which involve alternating brief bouts of highly intense anaerobic activity with rest periods, have comparable effects on AHN. Also, while less thoroughly investigated, individual genetic diversity in the overall response to physical activity is likely to play a key role in the effects of exercise on AHN. Physical exercise has been shown to improve health on average, although the benefits may vary from person to person, perhaps due to genetic differences. Maximal aerobic capacity and metabolic health may improve significantly with aerobic exercise for some people, while the same amount of training may have little effect on others. This review discusses the AHN's capability for peripheral nervous system (PNS) regeneration and central nervous system (CNS) control via physical exercise. Exercise neurogenicity, effective genes, growth factors, and the neurotrophic factors involved in PNS regeneration and CNS control were discussed. Also, some disorders that could be affected by AHN and physical exercise are summarized.

Cell-free therapy based on extracellular vesicles: a promising therapeutic strategy for peripheral nerve injury

Peripheral nerve injury (PNI) is one of the public health concerns that can result in a loss of sensory or motor function in the areas in which injured and non-injured nerves come together. Up until now, there has been no optimized therapy for complete nerve regeneration after PNI. Exosome-based therapies are an emerging and effective therapeutic strategy for promoting nerve regeneration and functional recovery. Exosomes, as natural extracellular vesicles, contain bioactive molecules for intracellular communications and nervous tissue function, which could overcome the challenges of cell-based therapies. Furthermore, the bioactivity and ability of exosomes to deliver various types of agents, such as proteins and microRNA, have made exosomes a potential approach for neurotherapeutics. However, the type of cell origin, dosage, and targeted delivery of exosomes still pose challenges for the clinical translation of exosome therapeutics. In this review, we have focused on Schwann cell and mesenchymal stem cell (MSC)-derived exosomes in nerve tissue regeneration. Also, we expressed the current understanding of MSC-derived exosomes related to nerve regeneration and provided insights for developing a cell-free MSC therapeutic strategy for nerve injury.

Vascular endothelial growth factor (VEGF) delivery approaches in regenerative medicine

The utilization of growth factors in the process of tissue regeneration has garnered significant interest and has been the subject of extensive research. However, despite the fervent efforts invested in recent clinical trials, a considerable number of these studies have produced outcomes that are deemed unsatisfactory. It is noteworthy that the trials that have yielded the most satisfactory outcomes have exhibited a shared characteristic, namely, the existence of a mechanism for the regulated administration of growth factors. Despite the extensive exploration of drug delivery vehicles and their efficacy in delivering certain growth factors, the development of a reliable predictive approach for the delivery of delicate growth factors like Vascular Endothelial Growth Factor (VEGF) remains elusive. VEGF plays a crucial role in promoting angiogenesis; however, the administration of VEGF demands a meticulous approach as it necessitates precise localization and transportation to a specific target tissue. This process requires prolonged and sustained exposure to a low concentration of VEGF. Inaccurate administration of drugs, either through off-target effects or inadequate delivery, may heighten the risk of adverse reactions and potentially result in tumorigenesis. At present, there is a scarcity of technologies available for the accurate encapsulation of VEGF and its subsequent sustained and controlled release. The objective of this review is to present and assess diverse categories of VEGF administration mechanisms. This paper examines various systems, including polymeric, liposomal, hydrogel, inorganic, polyplexes, and microfluidic, and evaluates the appropriate dosage of VEGF for multiple applications.

The food and biomedical applications of curcumin-loaded electrospun nanofibers: A comprehensive review

Encapsulating curcumin (CUR) in nanocarriers such as liposomes, polymeric micelles, silica nanoparticles, protein-based nanocarriers, solid lipid nanoparticles, and nanocrystals could be efficient for a variety of industrial and biomedical applications. Nanofibers containing CUR represent a stable polymer-drug carrier with excellent surface-to-volume ratios for loading and cell interactions, tailored porosity for controlled CUR release, and diverse properties that fit the requirements for numerous applications. Despite the mentioned benefits, electrospinning is not capable of producing fibers from multiple polymers and biopolymers, and the product’s effectiveness might be affected by various machine- and material-dependent parameters like the voltage and the flow rate of the electrospinning process. This review delves into the current and innovative recent research on nanofibers containing CUR and their various applications.

The stability and self-assembly of tri-calcium silicate and hydroxyapatite scaffolds in bone tissue engineering applications

The fabrication of scaffolds for bone tissue engineering (BTE) applications often involves the utilization of two distinct categories of biomaterials, namely calcium phosphates and calcium silicates. The selection of these materials is based on their biocompatibility, bioactivity, and mechanical characteristics that closely resemble those of natural bone. The present research examined the utilization of hydroxyapatite (HAP) and tri-calcium silicate (TCS), which are among the most commonly utilized materials in calcium phosphates and calcium silicates, in the context of bone scaffolding applications.

A supervised machine-learning analysis of doxorubicin-loaded electrospun nanofibers and their anticancer activity capabilities

Thanks to the diverse advantages of electrospun nanofibers, multiple drugs have been loaded in these nanoplatforms to be delivered healthily and effectively. Doxorubicin is a drug used in chemotherapy, and its various delivery and efficacy parameters encounter challenges, leading to the seeking of novel delivery methods. Researchers have conducted numerous laboratory investigations on the encapsulation of doxorubicin within nanofiber materials. This method encompasses various parameters for the production of fibers and drug loading, categorized into device-related, material-related, and study design parameters. This study employed a supervised machine-learning analysis to extract the influencing parameters of the input from quantitative data for doxorubicin-loaded electrospun nanofibers. The study also determined the significance coefficient of each parameter that influences the output results and identified the optimum points and intervals for each parameter. Our Support Vector Machine (SVM) analysis findings showed that doxorubicin-loaded electrospun nanofibers could be optimized through employing a machine learning-based investigation on the polymer solution parameters (such as density, solvent, electrical conductivity, and concentration of polymer), electrospinning parameters (such as voltage, flow rate, and distance between the needle tip and collector), and our study parameters, i.e., drug release and anticancer activity, which affect the properties of the drug-loaded nanofibers, such as the average diameter of fiber, anticancer activity, drug release percentage, and encapsulation efficiency. Our findings indicated the importance of factors like distance, polymer density, and polymer concentration, respectively, in optimizing the fabrication of drug-loaded electrospun nanofibers. These findings open up new roads for future design and production of drug-loaded polymeric nanofibers with desirable properties and performances by machine learning methods.

Injectable hyaluronic acid-based microcapsules loaded with human endometrial stem cells improves cardiac function after myocardial infarction

Therapeutic efficacy of human endometrial stem cells (hEnSCs) encapsulated in hyaluronic acid (HA)-based microcapsules for cardiac regeneration in a rat model of MI is investigated. Cell-enclosed microcapsules were made by loading hEnSCs within hydrogel membrane produced from modified HA possessing phenolic hydroxyl moieties (HA-Ph). The hEnSC-loaded HA-Ph microcapsules (≈150 μm) injected intramyocardially into the periinfarct area post-MI. The encapsulated cells showed mechanical stability and >87 % cell viability with cellular aggregation in size of about 100 μm until 7 days of culture. Transthoracic echocardiography evaluation indicated a significant increase in ejection fraction in encapsulated cells, compared to the other groups. Histological investigation of fibrosis and scar area by Masson trichrome and hematoxylin and eosin (H&E) staining illustrated less fibrosis and scarring area in the encapsulated cell group compared with the other groups. Furthermore, the cell-laden microcapsules significantly enhance expression intensities of actin and troponin as well as vascular endothelial-specific marker, all of which promote cardiac functions and contribute to a better therapeutic effect than the free-cell injection group in a rat model of MI. Our findings demonstrated that both hEnSCs and specifically hEnSC-loaded HA-based hydrogel vehicle can provide a promising novel therapy for functional restoration in MI instances.

Human endometrial stem cell‑derived small extracellular vesicles enhance neurite outgrowth and peripheral nerve regeneration through activating the PI3K/AKT signaling pathway

Nowadays, extracellular vesicles (EVs) such as exosomes participate in cell-cell communication and gain attention as a new approach for cell-free therapies. Recently, various studies have demonstrated the therapeutic ability of exosomes, while the biological effect of human endometrial stem cell (hEnSC)-derived small EVs such as exosomes is still unclear. Herein, we obtained small EVs from hEnSC and indicated that these small EVs activate the vital cell signaling pathway and progress neurite outgrowth in PC-12 cell lines. For this purpose, hEnSC-derived small EVs were extracted by ultracentrifuge and characterized by DLS, SEM, TEM, and western blot. Also, dil-staining of hEnSC-derived small EVs was done to determine the penetration of hEnSC-derived small EVs into PC12 cells. The MTT assay, scratch assay, and western blot assay were applied to PC12 cells that were exposed to different concentrations of small EVs (0, 50, 100, and 150 μg/ml). Our results demonstrated that small EVs significantly increased neurite outgrowth, proliferation, and migration in PC12 cells in a dose-dependent manner. Moreover, the analysis of western blots showed increased expression of the PI3k/AKT signaling pathway in PC12 cells exposed to hEnSC-derived small EVs in a dose-dependent manner. Also, the results of this study indicated that hEnSC-derived small EVs can enhance cell proliferation and migration and promote neural outgrowth by activating the PI3k/AKT signaling pathway. Accordingly, hEnSC-derived small EVs became an effective strategy for cell-free therapies. Altogether, these positive effects make hEnSC-derived small EVs a new efficient approach in regenerative medicine, especially for the cure of neural injury.

Investigation of pH‑dependent Paclitaxel delivery mechanism employing Chitosan‑Eudragit bioresponsive nanocarriers: a molecular dynamics simulation

Before embarking on any experimental research endeavor, it is advisable to do a mathematical computation and thoroughly examine the methodology. Despite the use of polymeric nanocarriers, the regulation of bioavailability and drug release at the disease site remains insufficient. Several effective methods have been devised to address this issue, including the creation of polymeric nanocarriers that can react to stimuli such as redox potential, temperature, pH, and light. The present study has been utilized all-atom molecular dynamics (AA-MD) and coarse-grained molecular dynamics (CG-MD) methods and illustrated the drug release mechanism, which is influenced by pH, for Chitosan- Eudragit bioresponsive nanocarriers. The aim of current work is to study the molecular mechanism and atomistic interactions of PAX delivery using a Chitosan-Eudragit carrier. The ability of Eudragit polymers to dissolve in various organic solvents employed in the process of solvent evaporation is a crucial benefit in enhancing the solubility of pharmaceuticals. This study investigated the use of Chitosan-Eudragit nanocarriers for delivering an anti-tumor drug, namely Paclitaxel (PAX). Upon analyzing several significant factors affecting the stability of the drug and nanocarrier, it has been shown that the level of stability is more significant in the neutral state than the acidic state. Furthermore, the system exhibits higher stability in the neutral state. The used Chitosan-Eudragit nanocarriers exhibit a stable structure under alkaline conditions, but undergo deformation and release their payloads under acidic conditions. It was demonstrated that the in silico analysis of anti-tumor drugs and carriers’ integration could be quantified and validated by experimental results (from previous works) at an acceptable level.

Resveratrol-loaded nanocarriers: Characteristics, sources, health effects, recent delivery systems, and their food and biomedical applications

Resveratrol (3,5,4′-trihydroxystilbene, RES) is a polyphenolic phytoalexin widely studied in the recent years due to its known several biological activities. In spite of the potential benefits of RES, its use is restricted because of its photosensitivity, low solubility, and fast metabolism, which intensely challenge its bioactivity and bioavailability. As RES is unstable against environmental conditions and due to its low bioavailability, multiple methods have been provided for the encapsulation of RES to facilitate its practical application in various fields. Encapsulation is introduced as an appropriate strategy in order to maintain stability, high absorption, and sustained release rate of RES. This review attempts to discuss the recent techniques used in loading RES in micro/nanocarriers and explain their wide applications in food and biomedical industries

Cartilage tissue engineering using decellularized biomatrix hydrogel containing TGF‑β‑loaded alginate microspheres in mechanically loaded bioreactor

Physiochemical tissue inducers and mechanical stimulation are both efficient variables in cartilage tissue fabrication and regeneration. In the presence of biomolecules, decellularized extracellular matrix (ECM) may trigger and enhance stem cell proliferation and differentiation. Here, we investigated the controlled release of transforming growth factor beta (TGF-β1) as an active mediator of mesenchymal stromal cells (MSCs) in a biocompatible scaffold and mechanical stimulation for cartilage tissue engineering. ECM-derived hydrogel with TGF-β1-loaded alginate-based microspheres (MSs) was created to promote human MSC chondrogenic development. Ex vivo explants and a complicated multiaxial loading bioreactor replicated the physiological conditions. Hydrogels with/ without MSs and TGF-β1 were highly cytocompatible. MSCs in ECM-derived hydrogel containing TGF-β1/MSs showed comparable chondrogenic gene expression levels as those hydrogels with TGF-β1 added in culture media or those without TGF-β1. However, constructs with TGF-β1 directly added within the hydrogel had inferior properties under unloaded conditions. The ECM-derived hydrogel group including TGF-β1/MSs under loading circumstances formed better cartilage matrix in an ex vivo osteochondral defect than control settings. This study demonstrates that controlled local delivery of TGF-β1 using MSs and mechanical loading is essential for neocartilage formation by MSCs and that further optimization is needed to prevent MSC differentiation towards hypertrophy.

Improving hemocompatibility in tissue-engineered products employing heparin-loaded nanoplatforms

The enhancement of hemocompatibility through the use of nanoplatforms loaded with heparin represents a highly desirable characteristic in the context of emerging tissue engineering applications. The significance of employing heparin in biological processes is unquestionable, owing to its ability to interact with a diverse range of proteins. It plays a crucial role in numerous biological processes by engaging in interactions with diverse proteins and hydrogels. This review provides a summary of recent endeavors focused on augmenting the hemocompatibility of tissue engineering methods through the utilization of nanoplatforms loaded with heparin. This study also provides a comprehensive review of the various applications of heparin-loaded nanofibers and nanoparticles, as well as the echniques employed for encapsulating heparin within these nanoplatforms. The biological and physical effects resulting from the encapsulation of heparin in nanoplatforms are examined. The potential applications of heparin-based materials in tissue engineering are also discussed, along with future perspectives in this field.

Boosting antitumor efficacy using docetaxel‑loaded nanoplatforms: from cancer therapy to regenerative medicine approaches

The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor solubility and significant side effects, docetaxel’s therapeutic potential has been significantly enhanced through its incorporation into nanoplatforms, such as nanofibers and nanoparticles. This advancement offers targeted delivery, controlled release, and improved bioavailability, dramatically reducing systemic toxicity and enhancing patient outcomes. Nanofibers provide a versatile scaffold for the controlled release of docetaxel, utilizing techniques like electrospinning to tailor drug release profiles. Nanoparticles, on the other hand, enable precise drug delivery to tumor cells, minimizing damage to healthy tissues through sophisticated encapsulation methods such as nanoprecipitation and emulsion. These nanotechnologies not only improve the pharmacokinetic properties of docetaxel but also open new avenues in regenerative medicine by facilitating targeted therapy and cellular regeneration. This narrative review highlights the transformative impact of docetaxel-loaded nanoplatforms in oncology and beyond, showcasing the potential of nanotechnology to overcome the limitations of traditional chemotherapy and pave the way for future innovations in drug delivery and regenerative therapies. Through these advancements, nanotechnology promises a new era of precision medicine, enhancing the efficacy of cancer treatments while minimizing adverse effects.

The progressive trend of modeling and drug screening systems of breast cancer bone metastasis

Bone metastasis is considered as a considerable challenge for breast cancer patients. Various in vitro and in vivo models have been developed to examine this occurrence. In vitro models are employed to simulate the intricate tumor microenvironment, investigate the interplay between cells and their adjacent microenvironment, and evaluate the effectiveness of therapeutic interventions for tumors. The endeavor to replicate the latency period of bone metastasis in animal models has presented a challenge, primarily due to the necessity of primary tumor removal and the presence of multiple potential metastatic sites. The utilization of novel bone metastasis models, including three-dimensional (3D) models, has been proposed as a promising approach to overcome the constraints associated with conventional 2D and animal models. However, existing 3D models are limited by various factors, such as irregular cellular proliferation, autofluorescence, and changes in genetic and epigenetic expression. The imperative for the advancement of future applications of 3D models lies in their standardization and automation. The utilization of artificial intelligence exhibits the capability to predict cellular behavior through the examination of substrate materials’ chemical composition, geometry, and mechanical performance. The implementation of these algorithms possesses the capability to predict the progression and proliferation of cancer. This paper reviewed the mechanisms of bone metastasis following primary breast cancer. Current models of breast cancer bone metastasis, along with their challenges, as well as the future perspectives of using these models for translational drug development, were discussed.

Integration of polysaccharide electrospun nanofibers with microneedle arrays promotes wound regeneration: A review

cellular growth and tissue rejuvenation, while microneedle arrays show potential for enhancing tissue regeneration and enhancing the efficacy of wound healing. The integration of electrospun nanofibers with microneedle arrays may be customized to effectively tackle particular obstacles in the fields of wound healing and drug delivery. However, some issues must be addressed before this paradigm may be fully integrated into clinical settings, including but not limited to ensuring the safety and sterilization of these products for transdermal use, optimizing manufacturing methods and characterization of developed products, larger-scale production, optimizing storage conditions, and evaluating the inclusion of multiple therapeutic and antimicrobial agents to increase the synergistic effects in the wound healing process. This research examines the combination of microneedle arrays with electrospun nanofibers to enhance the delivery of drugs and promote wound healing. It explores various kinds of microneedle arrays, the materials and processes used, and current developments in their integration with electrospun nanofibers.

Material extrusion additive manufacturing of poly(lactic acid)/ Ti6Al4V@calcium phosphate core-shell nanocomposite scaffolds for bone tissue applications

In this work, after preparing Ti6Al4V/Calcium phosphate (Ti64@CaP) core-shell nanocomposite via a solution-based process, by taking advantage of fused deposition modeling (FDM), porous poly(lactic acid) (PLA)- Ti64@CaP nanocomposite scaffolds were fabricated. Scanning electron microscope (SEM) showed that nanostructured calcium phosphate was distributed uniformly on the surface of Ti64 particles. Also, X-ray diffraction (XRD) indicated that calcium phosphate forms an octacalcium phosphate (OCP) phase. As a result of incorporating 6 wt% Ti64@CaP into the PLA, the compressive modulus and ultimate compressive strength values increased from 1.4 GPa and 29.5 MPa to 2.0 GPa and 53.5 MPa, respectively. Furthermore, the differential scanning calorimetry results revealed an increase in the glass transition temperature of PLA, rising from 57.0 to 62.4 ◦C, due to the addition of 6 wt% Ti64@CaP. However, it is worth noting that there was a moderate decrease in the crystallization and melting temperatures of the nanocomposite filament, which dropped from 97.0 to 89.5 ◦C and 167 to 162.9 ◦C, respectively. The scaffolds were seeded with human adipose tissue-derived mesenchymal stem cells (hADSCs) to investigate their biocompatibility and cell proliferation. Calcium deposition, ALP activity, and bone-related proteins and genes were also used to evaluate the bone differentiation potential of hADSCs. The obtained results showed that introducing Ti64@CaP considerably improved in vitro biocompatibility, facilitating the attachment, differentiation, and proliferation of hADSCs. Considering the findings of this study, the 3D-printed nanocomposite scaffold could be considered a promising candidate for bone tissue engineering applications.

In silico engineering and simulation of RNA interferences nanoplatforms for osteoporosis treating and bone healing promoting

Osteoporosis is a bone condition characterized by reduced bone mineral density (BMD), poor bone microarchitecture/mineralization, and/or diminished bone strength. This asymptomatic disorder typically goes untreated until it presents as a low-trauma fracture of the hip, spine, proximal humerus, pelvis, and/or wrist, requiring surgery. Utilizing RNA interference (RNAi) may be accomplished in a number of ways, one of which is by the use of very tiny RNA molecules called microRNAs (miRNAs) and small interfering RNAs (siRNAs). Several kinds of antagomirs and siRNAs are now being developed to prevent the detrimental effects of miRNAs. The goal of this study is to find new antagonists for miRNAs and siRNAs that target multiple genes in order to reduce osteoporosis and promote bone repair. Also, choosing the optimum nanocarriers to deliver these RNAis appropriately to the body could lighten up the research road. In this context, we employed gene ontology analysis to search across multiple datasets. Following data analysis, a systems biology approach was used to process it. A molecular dynamics (MD) simulation was used to explore the possibility of incorporating the suggested siRNAs and miRNA antagonists into polymeric bioresponsive nanocarriers for delivery purposes. Among the three nanocarriers tested [polyethylene glycol (PEG), polyethylenimine (PEI), and PEG-PEI copolymer], MD simulations show that the integration of PEG-PEI with has-mIR-146a-5p is the most stable (total energy = -372.84 kJ/mol, Gyration radius = 2.1084 nm), whereas PEI is an appropriate delivery carrier for has-mIR-7155. The findings of the systems biology and MD simulations indicate that the proposed RNAis might be given through bioresponsive nanocarriers to accelerate bone repair and osteoporosis treatment.

Bi-layered photocrosslinkable chitosan-curcumin hydrogel/soy protein nanofibrous mat skin substitute

This study examines the efficacy of a two-layer skin replacement composed of a visible-light photocrosslinkable chitosan hydrogel, either unmodified or incorporating curcumin, and overlaid with soy protein isolate (SPI) nanofibers. In order to achieve this objective, the synthesis of methacrylated chitosan was conducted, followed by the electrospinning of a nanofibrous mat using SPI. The resulting structures were then subjected to characterization using established engineering analyses. Following the utilization of the Taguchi method in experimental design, the optimal quantities of curcumin and riboflavin as a photo-initiator, as well as the curing time, were determined. Subsequently, an optimal hydrogel based on methacrylated chitosan was prepared, and the release rates of curcumin and riboflavin were measured over a specified duration. In order to evaluate the in vivo efficacy of the formulated constructs, four distinct experimental groups were included in the study. These groups consisted of an untreated control group, a group treated with hydrogel alone, a group treated with curcumin-loaded hydrogels, and a group treated with hydrogels coated with SPI electrospun mat. The wound healing potential was assessed through the examination of different histomorphometric parameters at two time points: 10 and 20 days following the surgical procedure. The concurrent application of curcumin loading and SPI nanofibrous mat is anticipated to yield notable beneficial alterations in the wound healing process.

Book

CHAPTER 4: Encapsulation: Shell and core / Principles of Biomaterials Encapsulation: Volume 2

Nanomaterials differ from their bulk forms in terms of characteristics, providing an excellent platform for developing novel modalities with unique properties. This is why nanoparticle (NP) production, characterization, and applications are among the most essential aspects of the broad field of nanotechnology. Researchers in the discipline have been focusing on NPs in recent years, since the shift from microparticles to NPs was shown to result in significant changes in a material’s physical and chemical characteristics.

CHAPTER 5: Encapsulation: Controlled drug delivery / Principles of Biomaterials Encapsulation: Volume 2

Pharmaceutical researchers have been utilizing biomaterials over the last 40 years to develop controlled drug delivery systems (DDSs). The reason for the extensive investigations on DDSs is that, without proper delivery, the majority of drugs are not adequately efficient and cause severe side effects. Proper encapsulation of drugs is one way to achieve controlled DDSs, while an encapsulation system provides protection for the drug from the surrounding environment in the body that might lead to its degradation or out-of-place activation. Therefore, encapsulation strategies can be tailored according to the specific characteristics of the drug molecules and their clinical applications to control the time of drug release, the site of drug release, and the trigger of drug release. Furthermore, encapsulation of drugs by biomaterials can increase drug solubility, enhance its penetration through membranes, and protect the drug against degradation. Therefore, DDSs have the potential to reduce the frequency of drug administration, improve patient compliance, and decrease the variability of bioavailability between patients.

CHAPTER 20: Encapsulation of cartilage cells / Principles of Biomaterials Encapsulation: Volume 2

Cartilage is an elastic structure located at both ends of the bones, facilitating joint movement. Unlike many other tissues in the body, the chondrocytes are relatively far apart and filled with intercellular substances consisting of a protein substance and a type of sugar. Chondrocytes are located in cavities called lacunae, and inside this intercellular tissue are thin filaments called fibrils. Cartilage tissue is quite similar to bone tissue in bearing loadings, but unlike bone, calcium does not deposit in the interosseous matter, which is, therefore, very elastic. Another difference between cartilage and bone is how the cells are nourished; cartilage has no arteries or nerves, and a fragile covering called the perichondrium covers the cartilage’s surface. Inside the joints, with the cartilage, there is a synovial fluid, in which oxygen and nutrients are released into the intercellular substance through the diffusion phenomenon and made available to the cells.

Chapter 29 - Development of 3D-printed biocompatible materials for meniscus substitution

This chapter highlights the recent progress in developing 3D-printed materials suitable for meniscus reconstruction. Similar to other organs and tissue, the meniscus is vulnerable and, in some cases, it is difficult to be healed. 3D printing gives a promising future to overcome challenges for patients with a meniscus injury. The role of biomaterials in the fabrication of 3D-printed scaffolds for meniscus substitution is undeniable. In other words, the mechanical, physicochemical, and biological properties of a meniscus-like scaffold can be optimized by changing the employed biomaterials. To achieve optimal properties, the combination of synthetic and natural biomaterials has always been recommended. Apart from these, scaffold geometry, optimal cell line selection, cell source, and growth factors can all stimulate cell differentiation into fibrocartilage, to create a suitable substitute for meniscus. By the way, creating a unique substitute for meniscus has a long way ahead and there are still challenges that are remained unsolved. As a result, the meniscus, despite its simple appearance, still needs further studies to establish a suitable substitute with suitable biological properties, which could be due to the location of this tissue and the constant pressure.

Chapter 17 - 3D inverse finite element modeling

In multiple medical applications, the geometry of tissues or organs is often generated from in vivo imaging, making physically accurate patient-specific biomechanical models of utmost relevance. When the outcomes of interest are connected to tissue stresses or the distribution of contact pressure, the FEM analysis technique is frequently the chosen method in purely mechanical models. Rapid and accurate FEM model calibration in a 3D complex environment requires developing inverse analysis techniques. Commercial and open-source FEM programs often only allow calibration of a single model to a single set of experimental data, limiting the variety of comparisons that may be made. However, due to the inherent inconsistency of experimental results, it is sometimes helpful to do simultaneous calibration across several specimens or experimental measurements, going beyond the capabilities of existing instruments. However, biological structures often assume a distorted shape when subjected to external loadings. This calls for an inverse analysis strategy to ascertain the stress distribution of the previously known deformed condition. This chapter discusses 3D inverse finite element modeling, reviewing the research in this area and the challenges against this branch of science.