Background: Liver, as a vital organ, is responsible for a wide range of biological functions to maintain homeostasis and any type of damages to hepatic tissue contributes to disease progression and death. Viral infection, trauma, carcinoma, alcohol misuse and inborn errors of metabolism are common causes of liver diseases are a severe known reason for leading to end-stage liver disease or liver failure. In either way, liver transplantation is the only treatment option which is, however, hampered by the increasing scarcity of organ donor. Over the past years, considerable efforts have been directed toward liver regeneration aiming at developing new approaches and methodologies to enhance the transplantation process. These approaches include producing decellularized scaffolds from the liver organ, 3D bio-printing system, and nano-based 3D scaffolds to simulate the native liver microenvironment. The application of small molecules and micro-RNAs and genetic manipulation in favor of hepatic differentiation of distinct stem cells could also be exploited. All of these strategies will help to facilitate the application of stem cells in human medicine. This article reviews the most recent strategies to generate a high amount of mature hepatocyte-like cells and updates current knowledge on liver regenerative medicine.

Cancer is a main public health problem that is known as a malignant tumor and out-of-control cell growth, with the potential to assault or spread to other parts of the body. Recently, remarkable efforts have been devoted to develop nanotechnology to improve the delivery of anticancer drug to tumor tissue as minimizing its distribution and toxicity in healthy tissue. Nanotechnology has been extensively used in the advance of new strategies for drug delivery and cancer therapy. Compared to customary drug delivery systems, nano-based drug delivery method has greater potential in different areas, like multiple targeting functionalization, in vivo imaging, extended circulation time, systemic control release, and combined drug delivery. Nanofibers are used for different medical applications such as drug delivery systems.

Certain polymeric materials such as polyurethanes (PUs) are the most prevalent class of used biomaterials in regenerative medicine and have been widely explored as vascular substitutes in several animal models. It is thought that PU-based biomaterials possess suitable hemo-compatibility with comparable performance related to the normal blood vessels. Despite these advantages, the possibility of thrombus formation and restenosis limits their application as artificial functional vessels. In this regard, various surface modification approaches have been developed to enhance both hemo-compatibility and prolong patency. While critically reviewing the recent advances in vascular tissue engineering, mainly PU grafts, this paper summarizes the application of preferred cell sources to vascular regeneration, physicochemical properties, and some possible degradation mechanisms of PU to provide a more extensive perspective for future research.

Biocompatible, biodegradable, and injectable hydrogels are a novel and promising approach for bone regeneration. In this study, poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) (PCL-PEG-PCL), PCL-PEG-PCL-gelatin (Gel), PCL-PEG-PCL-Gel/nano-hydroxyapatite (nHA) injectable hydrogels were synthesized and evaluated in a mouse model of subcutaneous transplantation after 14 days. PCL-PEG-PCL-Gel and PCL-PEG-PCL-Gel/nHA hydrogels were fabricated with in situ precipitation method. Structure, intermolecular interaction, and the reaction between the PCL-PEG-PCL, Gel, and nHA were evaluated using a scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (H-NMR), and carbon nuclear magnetic resonance (C-NMR). Fourteen days after subcutaneous injection, the existence of an immune system reaction was investigated using Hematoxylin and Eosin (H&E) staining. Using immunofluorescence imaging, the number of CD68+ cells was determined in the periphery of the hydrogel. The CD8/CD4 lymphocyte ratio was also calculated in blood samples. We monitored the expression of CCL-2, BCL-2, IL-10, and CD31 using real-time PCR assay. The chemical evaluation revealed the successful integration of Gel and nHA to the PCL-PEG-PCL backbone. Histological examination showed the lack of inflammation at the site of injection. No toxicological effects were determined in hepatic and renal tissues. The addition of nHA to the PCL-PEG-PCL-Gel decreased biodegradation time. None of the hydrogels caused statistically significant differences in the number of CD68 cells (p > 0.05). The CD8/CD4 lymphocyte ratio remained unchanged in all groups (p > 0.05). Compared to the PCL-PEG-PCL group, the addition of nHA and Gel increased the expression of CCL-2, BCL-2, IL-10, and CD31 (p < 0.05). In conclusion, the current study showed that PCL-PEG-PCL-Gel/nHA hydrogels could be used in in vivo conditions without prominent toxic effects and inflammatory responses.

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In the past decade, microneedle-based drug delivery systems showed promising approaches to become suitable and alternative for hypodermic injections and can control agent delivery without side effects compared to conventional approaches. Despite these advantages, the procedure of microfabrication is facing some difficulties. For instance, drug loading method, stability of drugs, and retention time are subjects of debate. Besides, the application of novel refining fabrication methods, types of materials, and instruments are other issues that need further attention. Herein, we tried to summarize recent achievements in controllable drug delivery systems (microneedle patches) in vitro and in vivo settings. In addition, we discussed the influence of delivered drugs on the cellular mechanism and immunization molecular signaling pathways through the intradermal delivery route. Understanding the putative efficiency of microneedle patches in human medicine can help us develop and design sophisticated therapeutic modalities.

Horseradish peroxidase (HRP)-catalyzed hydrogels are considered to be an important platform for tissue engineering applications. In this study, we investigated the chondrogenic capacity of phenolated (1.2%) alginate-(0.5%) collagen hydrogel on human amniotic mesenchymal stem cells after 21 days. Using NMR, FTIR analyses, and SEM imaging, we studied the phenolation and structure of alginate-collagen hydrogel. For physicochemical evaluations, gelation time, mechanical properties, swelling, and degradation rate were assessed. The survival rate was monitored using the MTT assay and DAPI staining. Western blotting was performed to measure the chondrogenic differentiation of cells. NMR showed successful phenolation of the alginate-collagen hydrogel. FTIR exhibited the interaction between the functional groups of collagen with phenolated alginate. SEM showed the existence of collagen microfibrils in the alginate-collagen hydrogel. Compared to phenolated alginate, the addition of collagen increased hydrogel elasticity by 10%. Both swelling rate and biodegradability were reduced in the presence of collagen. We noted an increased survival rate in phenolated alginate-collagen compared to the control cells (p < 0.05). Western blotting revealed the increase of chondrocyte-associated proteins such as SOX9 and COL2A1 in phenolated-alginate-collagen hydrogels after 21 days. These data showed that phenolated alginate-collagen hydrogel is an appropriate 3 D substrate to induce chondrogenic capacity of human mesenchymal stem cells.