Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel.

Fabrication of the FGF1-functionalized sericin hydrogels with cell proliferation activity for biomedical application using genetically engineered Bombyx mori (B. mori) silk

Global Challenges in Stem Cell Research and the Many Roads Ahead

Hyaluronic acid as a macromolecular crowding agent for production of cell-derived matrices

Regenerative medicine offers the potential to replace or repair different types of cells within damaged or defective tissues. Tissue engineering and cell therapy are promising approaches in regenerative medicine for the aging population. Particularly, treatments using therapeutic biomaterials are attractive methods for osteoarthritis (OA), which is the most common arthropathy. It is characterized by the gradual loss of articular cartilage that covers the ends of bones. Articular cartilage acts as a cushion against joint impact and enables flexible joint motion, but it has a very limited capacity for self-regeneration. Regenerative medicine technologies show promising results in cartilage regeneration using the transplantation of natural hydrogels containing various types of cells. Despite some clinical success in simple cartilage regeneration, many challenges remain in developing technologies to prevent OA progression and cartilage degradation. Injectable hydrogels have been of interest in minimal invasive treatment for OA as a cell delivery vehicle or as an inflammation modulator. Recently, the use of natural hydrogels has expanded into the areas of pain relief and reducing inflammation in OA patients. These scientific efforts have led to an effective, injectable hydrogel system to control inflammation and immunomodulation related to cartilage degradation. In this chapter, state-of-the-art tissue engineering technologies and the application of injectable natural hydrogels for OA treatment have been reviewed.

Injectable hydrogels have previously demonstrated potential as a temporary scaffold for tissue regeneration or as a delivery vehicle for cells, growth factors, or drugs. However, most injectable hydrogel systems lack a microporous structure, preventing host cell migration into the hydrogel interior and limiting spreading and proliferation of encapsulated cells. Herein, an injectable microporous hydrogel assembled from gelatin/gelatin methacryloyl (GelMA) composite microgels is described. Microgels are produced by a water-in-oil emulsion using a gelatin/GelMA aqueous mixture. These microgels show improved thermal stability compared to GelMA-only microgels and benefit from combined photopolymerization using UV irradiation (365 nm) in the presence of a photoinitiator (PI) and enzymatic reaction by microbial transglutaminase (mTG), which together enable fast curing and tissue adhesion of the hydrogel. The dual-crosslinking approach also allows for the reduction of PI concentration and minimizes cytotoxicity during photopolymerization. When applied for in situ cell encapsulation, encapsulated human dermal fibroblasts and human mesenchymal stem cells (hMSCs) are able to rapidly spread and proliferate in the pore space of the hydrogel. This hydrogel has the potential to enhance hMSC anti-inflammatory behavior through the demonstrated secretion of prostaglandin E2 (PGE2) and interleukin-6 (IL-6) by encapsulated cells. Altogether, this injectable formulation has the potential to be used as a cell delivery vehicle for various applications in regenerative medicine.

Lentivirus Immobilization to Nanoparticles for Enhanced and Localized Delivery From Hydrogels

Low Oxygen Tension and Synthetic Nanogratings Improve the Uniformity and Stemness of Human Mesenchymal Stem Cell Layer

A highly transparent, elastic, injectable sericin hydrogel induced by ultrasound

The application of sericin hydrogels is limited mainly due to their poor mechanical strength, tendency to be brittle and inconvenient sterilization. To address these challenges, a sericin hydrogel exhibiting outstanding physical and chemical properties along with cytocompatibility was prepared through crosslinking genipin with degraded sericin extracted from fibroin deficient silkworm cocoons by the high temperature and pressure method. Our reported sericin hydrogels possess good elasticity, injectability, and robust behaviors. The 8% sericin hydrogel can smoothly pass through a 16 G needle. While the 12% sericin hydrogel remains intact until its compression ratio reaches 70%, accompanied by a compression strength of 674 kPa. 12% sericin hydrogel produce a maximum stretch of 740%, with breaking strength and tensile modulus of 375 kPa and 477 kPa respectively. Besides that, the hydrogel system demonstrated remarkable cell-adhesive capabilities, effectively promoting cell attachment and, proliferation. Moreover, the swelling and degradation behaviors of the hydrogels are pH responsiveness. Sericin hydrogel releases drugs in a sustained manner. Furthermore, this study addresses the challenge of sterilizing sericin hydrogels (sterilization will inevitably lead to the destruction of their structures). In addition, it challenges the prior notion that sericin extracted under high temperature and pressure is difficult to directly cross-linked into a stable hydrogel. This developed hydrogel system in this study holds promise to be a new multifunctional platform expanding the application area scope of sericin.

Cardiac tissue engineering is an emerging field that may hold great promise for advancing the treatment of heart diseases. Cardiac tissue engineering is in its infancy, and the overall field of tissue engineering, which was formalized in the late 1980s at conferences and workshops sponsored by the National Science Foundation, is still new enough to warrant some description. By broad definition, tissue engineering involves the construction of tissue equivalents through the manipulation and combination of living cells and biomaterials. It is a multidisciplinary field combining diverse aspects of the life sciences, engineering, and clinical medicine. The overall goal of tissue engineering is to develop tissue equivalents for use in the repair, replacement, maintenance, or augmentation of tissues or organs. Although some aspects of cardiac tissue engineering research have been ongoing for generations, albeit without being known as such, directed efforts in the field are only beginning. The main justification for cardiac tissue engineering initiatives is straightforward: congenital and acquired heart diseases are substantial health problems, and there is a limited amount of donor tissue for use in surgical repairs. Heart defects are the most common congenital defect and are the leading cause of death in the first year of life.1,2⇓ Congenital heart defects may occur in as many as 14 of every 1000 live births,3 and approximately 25 000 surgical procedures are performed each year to correct them. Acquired heart diseases also have a profound effect on the population, and despite tremendous advances in medical and surgical treatments, it is estimated that each year 20 000 to 40 000 Americans could benefit from a heart transplant.4 Unfortunately, fewer than 2500 heart transplants are performed each year.4,5⇓ One of the principal reasons for the disparity between patient need and procedures performed is the lack of …

Regenerative medicine has received potential attention around the globe, with improving cell performances, one of the necessary ideas for the advancements of regenerative medicine. It is crucial to enhance cell performances in the physiological system for drug release studies because the variation in cell environments between in vitro and in vivo develops a loop in drug estimation. On the other hand, tissue engineering is a potential path to integrate cells with scaffold biomaterials and produce growth factors to regenerate organs. Scaffold biomaterials are a prototype for tissue production and perform vital functions in tissue engineering. Silk fibroin is a natural fibrous polymer with significant usage in regenerative medicine because of the growing interest in leftovers for silk biomaterials in tissue engineering. Among various natural biopolymer-based biomaterials, silk fibroin-based biomaterials have attracted significant attention due to their outstanding mechanical properties, biocompatibility, hemocompatibility, and biodegradability for regenerative medicine and scaffold applications. This review article focused on highlighting the recent advancements of 3D printing in silk fibroin scaffold technologies for regenerative medicine and tissue engineering.

Embryonic stem cells (ESCs) have received tremendous attention because of their potential applications in regenerative medicine. Over the past two decades, intensive research has not only led to the generation of various types of cells from ESCs that can be potentially used for the treatment of human diseases but also led to the formation of new concepts and breakthroughs that have significantly impacted our understanding of basic cell biology and developmental biology. Recent studies have revealed that ESCs and other types of pluripotent cells do not have a functional interferon (IFN)-based anti-viral mechanism, challenging the idea that the IFN system is developed as the central component of anti-viral innate immunity in all types of cells in vertebrates. This finding also provided important insight into a question that has been uncertain for a long time: whether or not the RNA interference (RNAi) anti-viral mechanism operates in mammalian cells. An emerging paradigm is that mammals may have adapted distinct anti-viral mechanisms at different stages of organismal development; the IFN-based system is mainly used by differentiated somatic cells, while the RNAi anti-viral mechanism may be used in ESCs. This paper discusses the molecular basis and biological implications for mammals to have different anti-viral mechanisms during development.

پژوهش‌های کنونی نشان می‎دهد، نانولوله‎های کربنی (CNTs) به‌عنوان زیست‌مواد، پتانسیل بسیار زیادی برای کاربردهای پزشکی ترمیمی دارند. تمرکز پزشکی ترمیمی بر روش‎های توسعه‌یافته‎ای است که برای ایجاد بافت‎های کارکردی، ترمیم یا جایگزینی بافت‎ها و اندام‎های از دست رفته به علت زخم یا بیماری، اعمال می‌شوند. در این راستا، خواص ساختاری و مکانیکی CNTها آن‎ها را برای استفاده به‌عنوان کامپوزیت در مهندسی بافت کاربردی ساخته است. CNTها می‎توانند به‌عنوان حامل در دارورسانی و ژن‌درمانی به‌کار روند، بنابراین برای کارهای درمانی در پزشکی ترمیمی مناسب‌اند. سطح بیرونی نانولوله‎های کربنی را می‎توان برای دارورسانی هدفمند و عوامل تصویربرداری عامل‎دار کرد. سایر خواص فیزیکی ذاتی این نانولوله‎ها را می‎توان برای کاربردهای درمانی و تصویربرداری نیز استفاده کرد. کاربرد نانولوله‌های کربنی به‌عنوان عوامل تمایز جلوه در تصویربرداری به اثبات رسیده است. در دهه گذشته، نانولوله‎های کربنی با توجه به خواص منحصر به فرد و متنوع آن‌ها برای مجموعه‌ای از کاربردها بررسی و مطالعه شده‌اند. این نانولوله‌ها در زمینه پزشکی ترمیمی نویدبخش بهبود خواص داربست‌های مهندسی بافت، دارورسانی و تصویربرداری از بافت‌های مهندسی هستند. در این مقاله، آخرین پیشرفت‎ها و تحولات کاربردهای نانولوله‎های کربنی در پزشکی ترمیمی مرور شده است.

THE key focus of regenerative medicine lies in the reconstitution of damaged or dysfunctional cells, tissues, or organs. Stimulation of the body's own regenerative potential, the connection to artificial materials and surface structures and extracorporeal tissue engineering of cells and tissues are particular challenges (1, 2). Success in the derivation of stem cell lines has opened up a new area of research in biomedicine. Human stem cells not only raise hope for cell replacement therapies but also provide a potential novel system to better understand early human normal development, model human abnormal development and disease, and perform drug screening and toxicity studies. The realization of these potentials, however, depends on expanding our knowledge about the cellular and molecular mechanisms that regulate self renewal and lineage specification. Cytomics has received great attention during the last several years as it allows us to quantitatively analyze a great number of individual cells, their constituents, and their intracellular and functional interactions in cellular systems (cytomes) (3-12). Exhaustive knowledge extraction from multiparametric assays and multiple tests are the prerequisite for cytomics. This novel approach for unsupervised data analysis opens the chance to find the most important parameters which describe best the cell systems. Individual cells of an organ may be specifically equipped to perform specific tasks. Deciphering cell systems on the individual cell level may yield key information to understand function or dysfunction. A combination of state-of-the-art approaches, including cytomics, proteomics, and genomics, will be instrumental in moving the field forward, ultimately lending invaluable knowledge to research areas in regenerative medicine. Analyzing the data about cellular structures, cytomics—the systems biological discipline for cell population analysis—provides a plethora of information and is the ideal partner of regenerative medicine. Realizing the idea “from the molecule to the patient” gives an opportunity to speed up the introduction of this knowledge and offers chemical compounds, proteins, and other biomolecules, cells and tissues as instruments and products for a wide variety of biotechnological and biomedical applications. Cytomics combines different disciplines and will promote the development of innovative therapies and diagnostic methods. Regenerative medicine can be improved by the precision of the measurements with focus on single cell analysis. Analyzing from cell constituents to whole body imaging techniques, cytometry covers the field from molecules through subcellular components, cells, tissues, and organs to live analysis of small animals (13, 14). It harbors the promise to substantially impact on various fields of biomedicine, like regenerative and predictive medicine (3, 5). As the number of scientific data is rising exponentially, new data analysis tools and strategies for cytomics take the lead and get closer to application. Cytomics may strongly support the quantitative data selection, thus strengthening the rationale for biomedicine. This year's 14th Leipziger Workshop highlighted applications in regenerative medicine and focused on how cytometry has contributed to the characterization of primary cells, cell cultures, and their development. The Leipziger Workshop series began in 1995. From 2003 on, it embraced cytomics as its major topic (15). After the first cytomics workshop, we started to combine cytomics with various biomedical disciplines: regenerative and predictive medicine of cardiovascular disease (2004) (5), systems biology and clinical cytomics (2005) (16), cytomics and the human cytome project (2006) (17), cytomics and translational medicine (2007) (18, 19), and cytomics and nanobioengineering (2008) (20). Consequently, the key aspects of the 14th Leipziger Workshop from April 2–4, 2009 in Leipzig (www.leipziger-workshop.de) were cytomics and regenerative medicine. The high relevance of this combination of two biomedical disciplines with a strong standing in technology was highly appreciated. Over 90 scientists attended this year's meeting from more than 10 countries. It included keynote lectures and tutorials; there were overall 33 oral and 17 poster presentations (see abstracts). So far, this has been one of the most successful meetings in the history of the Leipziger Workshop. The number of participants has constantly increased over the last several years and will further prosper in future. The high attendance and anticipation of the workshop shows the increased demand and interest in cytomics. This year's workshop received substantial support from the Biological and Biomedical Center of the University of Leipzig (BBZ, www.bbz.uni-leipzig.de), the newly founded Translational Center for Regenerative Medicine (TRM, www.trm.uni-leipzig.de) Leipzig and several exhibitors who were also directly involved in the teaching program (www.leipziger-workshop.de).

It is documented that human mesenchymal stem cells (hMSCs) can be differentiated into various types of cells to present a tool for tissue engineering and regenerative medicine. Thus, the preservation of stem cells is a crucial factor for their effective long-term storage that further facilitates their continuous supply and transportation for application in regenerative medicine. Cryopreservation is the most important, practicable, and the only established mechanism for long-term preservation of cells, tissues, and organs, and engineered tissues; thus, it is the key step for the improvement of tissue engineering. A significant portion of MSCs loses cellular viability while freeze-thawing, which represents an important technical limitation to achieving sufficient viable cell numbers for maximum efficacy. Several natural and synthetic materials are extensively used as substrates for tissue engineering constructs and cryopreservation because they promote cell attachment and proliferation. Rho-associated kinase (ROCK) inhibitors can improve the physiological function and postthaw viability of cryopreserved MSCs. This review proposes a crosstalk between substrate topology and interaction of cells with ROCK inhibitors. It is shown that incorporation of ionic nanoparticles in the presence of an external electrical field improves the generation of ROCK inhibitors to safeguard cellular viability for the enhanced cryopreservation of engineered tissues.