Current Tissue Engineering (Discontinued) - Volume 2, Issue 1, 2013

Because of the rising demand for replacing failure organs in transplantation therapy, tremendous efforts have been made to reconstruct entire organs using tissue engineering. However, most successes have been restricted in avascular or thin tissues. For thicker tissues, oxygen and nutrients are harder to diffuse into implants and sustain cellular viability. Therefore, numerous attempts have been made to induce vascularization in engineered tissues, which focus on cellcell and cell-scaffold interactions, respectively. This review focuses on current researches in the field of biomimetic scaffold promoting the cell-scaffold interactions. Bioactive molecules, such as angiogenic growth factors, extracellular matrix proteins or adhesive peptides derived from them, either released from or attached to various scaffolds to stimulate endothelial cells to form lumen and vascular sprouting in vitro. With or without pro-seeding, the scaffolds could induce neovascularization and microvascular network anastomosis with the host circulation in vivo in varying degrees. This strategy is a big step forward towards the promotion of angiogenesis in vascular-insufficient tissues. Based on the achieved developments, more effective strategies have been developed for attaining the functional vascularized constructs.

Current stem cell research greatly depends on suitable in vitro-cultivation approaches, enabling expansion, differentiation, cryopreservation or genetic modification of stem cells outside the organism. Particularly regarding neurodegenerative diseases, regeneration of complex injuries or cancer, this already great field of applications is even broadened by in vitro-culture approaches for stem cell-based therapy. Here, 2D-concepts of cultivation focus on cell differentiation or short-time expansion for further transplantation as well as the elucidation of molecular mechanisms of a certain disease for drug targeting. However, latest studies suggest potential beneficial effects of 3D cultivation strategies. In contrast to 2D-culture, the conditions of the endogenous stem cell niche are mirrored more closely, leading to improved cellular viability and differentiation behavior. The use of 3D-cultivated stem cell-products may provide the advantages of direct transplantation, enhanced graft adherence and higher cellular loading densities within the transplant. Thus, together with the increased differentiation potential of stem cells under such conditions, 3D-culture may provide a powerful tool for regenerative medicine. Here, we summarize current 3D-cultivation approaches for adult, embryonic and cancer stem cells, highlighting their potential scientific and clinical impacts.

In recent years, considerable attention has been given to functional biomaterials (BMs) for their potential applications in the biomedical field. Among them, the biopolymer chitosan (CTS) has been receiving increasing attention. Owing to its unique and appealing biological properties, such as biocompatibility, tunable biodegradability, antimicrobial, and wound healing activity, it is considered suitable for biomedical applications. CTS and its derivatives are promising candidates as a supporting material for tissue engineering applications due to their porous structure, gel forming properties, ease of chemical modification and high affinity to in vivo macromolecules. These BMs showed great potential due to their polyelectrolyte properties, the presence of reactive functional groups, high adsorption capacity, and anti-tumor effect. Remarkably, the application of CTS has been gaining attention in the regenerative medicine due to its structural similarity to glycosaminoglycans, which are components of a tissue’s extracellular matrix. In this context, this review provides the recent development in potential applications of CTS and its derivatives in different domains of biomedicine, pharmaceuticals and personal care products (PPCPs). The applications of CTS and their derivatives are discussed with particular emphasis on tissue engineering, drug and gene delivery, wound healing, antimicrobial, anti-tumor activities and in personal care products. This review also discusses the various attributes of CTS required in biomedical and pharmaceutical applications.

Cartilages have a very little capability for self-repair after injury. Tissue engineered bio-scaffolds seeded with the mesenchymal stem cell (MSC)-derived chondrocytes are viewed as a promising therapeutic modality for regeneration enhancement of the damaged cartilages. Under appropriate culture conditions, MSCs can differentiate into chondrocytes and secrete collagen (Col2a1 (IIb)), proteoglycans (aggrecan (Agc)), non-collagenous proteins, and tissue fluid to lead to the development of zones of organization in cartilages. Bioreactor can provide the mechanical and chemical stimuli along with the required cytokines (Cytl1, TNF-α, ROS), mitogen (IL-18, FGF-2, Protein Kinase C-Erk-1/2 and p38), and growth factors (IGF-1, TGF-β, parathyroid hormone-related peptide, BMP-2) to modulate chondrogenesis and grow threedimensional (3-D) tissue. It also allows changes in the culture environment to affect the kinetics and properties of tissue growth, in a well-defined fluid regime to elucidate mechanotransduction pathways involving shear, perfusion, and compression force and tissue growth kinetics. This review discusses various signalling factors in the regulation of chondrogenesis from MSCs and elaborates various types of bioreactors that may provide optimal culture milieu and mechanical stress which are used to develop the tissue-engineered cartilages for their clinical application.

Majority current bone tissue biomimetics are based on collagen containing composites since the collagen is a major organic component of the natural extra cellular matrix (ECM). Two main types of biomimetic composites, based on: i) fibriliar or ii) electrospun collagen are in the focus of this review. It includes a brief presentation of the composition, hierarchical structure and formation of natural bone, as a base of the bone biomimetic design strategy. Requirements to substituting biomaterials (synthetic bone scaffolds and grafts) analogous to natural bone in terms of composition, structure (at micro-, nano- or molecular level) and function are also included in this review.

Various hepatic models are currently used as in vitro models alternative to in vivo animal studies for toxicity assessment. Most of these models including the in vivo animal models are limited in the accurate prediction of toxicity. Major reasons are inadequate in vitro culture techniques and in case of in vivo animal models, the species specific differences in the metabolism of xenobiotics. Conventional 2D hepatocyte cultures rapidly lose liver-like functionality leading to high discrepancies between experimental in vitro data and actual in vivo situation. In contrast, 3D liver cell cultures mimic the in vivo tissue and show improved organotypic functionality allowing realistic assessment of drug metabolism, and adverse/toxic effects. Such 3D engineered models, by ensuring prolonged viability and functionality, can also be applied for repeated dose testing in chronic toxicity studies. In this review, we focus on recent advances in the development and characterization of three-dimensional in vitro liver models. We discuss different 3D systems from small-scale bioreactors and spheroids to micro-structured devices and highlight their application in toxicological studies.