Bioreactor-Based Tumor Tissue Engineering.

This review focuses on modeling of cancer tumors using tissue engineering technology. Tumor tissue engineering (TTE) is a new method of three-dimensional (3D) simulation of malignant neoplasms. Design and development of complex tissue engineering constructs (TECs) that include cancer cells, cell-bearing scaffolds acting as the extracellular matrix, and other components of the tumor microenvironment is at the core of this approach. Although TECs can be transplanted into laboratory animals, the specific aim of TTE is the most realistic reproduction and long-term maintenance of the simulated tumor properties in vitro for cancer biology research and for the development of new methods of diagnosis and treatment of malignant neoplasms. Successful implementation of this challenging idea depends on bioreactor technology, which will enable optimization of culture conditions and control of tumor TECs development. In this review, we analyze the most popular bioreactor types in TTE and the emerging applications.

[The morphological and morphometric study of amianthoid transformation of the costal cartilage in health and in keeled chest deformity in children]. / Morfologicheskoe i morfometricheskoe issledovanie amiantoidnoi transformatsii rebernykh khryashchei v norme i pri kilevidnoi deformatsii grudnoi kletki u detei.

Amianthoid transformation (AT) is the accumulations of abnormal collagen structures (amianthoid fibers) in the hyaline cartilages, tumors, and tendons. Neither functional value of costal cartilage matrix AT, nor its role in the pathogenesis of congenital chest deformities is known now. AIM: to examine the morphological features of AT in the costal cartilage of children with the normal and keeled chest. SUBJECTS AND METHODS: Costal cartilages were studied in 6 children with the normal chest (autopsy material) and in 5 ones with keeled chest (surgical material). Tissue fragments were fixed in 10% neutral formalin and embedded in compacted paraffin. The sections were stained with hematoxylin and eosin, picrofuchsin by van Gieson, with picrosirius, toluidine blue and by the Malaurie method modified by Gallego. The specimens were examined by light, phase-contrast, dark-field, fluorescence, and polarization microscopy. The frequency of AT sites and their area were morphometrically studied and the findings were then statistically processed. RESULTS: Various types of AT in the costal cartilages were described as both the normal and keeled chest. According to their morphological features, classic, fine-fiber, twisted, and intralacunar types were identified. There were statistically significant increases in the incidence of all types (except the intralacunar one) and in the area of the fine-fiber AT type in keeled chest deformity as compared to health. There were positive correlations between the area of classic, intralacunar, and twisted types in both groups and between the area of a classic type and age in the controls. CONCLUSION: A classification of AT areas varying in structures in health and disease has been given for the first time; their relation to each other and to the presence of keeled deformity shown, which, in our opinion, suggests that AT is implicated in the pathogenesis of the disease.

[TISSUE-ENGINEERED SUBSTITUTION URETHROPLASTY BASED ON DECELLULARIZED VASCULAR MATRIX AND AUTOLOGOUS CELLS OF THE BUCCAL MUCOSA: THE FIRST EXPERIENCE].

Urethral strictures and anomalies remain a challenging urological problem. Reconstructive plastic surgery has been shown to be the most effective way to treat them. There are two main types of urethroplasty: anastomosis (anastomotic urethroplasty) and expansion of the urethral lumen using of flaps and grafts (substitution urethroplasty). Currently the ideal material for substitution urethroplasty does not exist. Tissue engineering of the urethra seems to be one of the most promising approaches to address this problem. Various tissues-engineering techniques were proposed for substitution urethroplasty. In this study, tissue-engineering design was based on the decellularized cadaveric arterial wall. The study results demonstrated the feasibility of creating stable tissue-engineered structures with autologous cultured epithelial cells of the buccal mucosa and decellularized matrix from human cadaveric arterial wall (DMCAW). There was a complete engraftment of tissue-engineering design based on DMCAW and buccal mucosa cells, used for substitution urethroplasty in a patient with the bulbar urethral stricture. Postoperatively (within 4 months after surgery) no complications and/or adverse events were observed. However, in the late postoperative period (12 months) there was recurrence of urethral stricture in the middle of the tissue-engineering design and the native urethra that warranted another surgery. Tissue-engineering design based on DMCAW and autologous buccal mucosa is safe as a material for substitution urethroplasty. Further research is required to ascertain the effectiveness of the method.

[PLGA mesh-collagen hybrid scaffold and tissue-engineered product in substitution urethroplasty: experimental validation].

Urethral strictures are a pressing issue in modern medicine. Substitution urethroplasty is considered one of the most effective treatment methods. However, despite the surgery showing good results, many problems remain unresolved, one being substitute material deficiency in extensive or recurrent strictures, as well as in cases requiring multistage surgeries, including those used to treat hypospadias. Graft removal also leaves the donor area prone to diseases and increases the length of surgery leading to a higher risk of intra- and postoperative complications. Tissue engineering (namely tissue-engineered products comprised of scaffolds and cells) may be a useful tool in dealing with these issues. The authors assessed the characteristics of a novel hybrid scaffold created from "reconstructed" collagen and a poly(lactic-co-glycolic acid) mesh. The resulting composite product showed good mechanical properties and functional performance. The hybrid scaffold was non-cytotoxic and provided an adequate base for cell adhesion and proliferation. Biodegradation resulted in the scaffold being replaced by urothelium and urethral mucosa. The newly formed tissues possessed adequate structural and functional properties. Only one rabbit out of 12 developed urethral stricture at the site of scaffold implantation. The above-mentioned facts suggest that the novel hybrid scaffold is a promising tissue-engineered product with potential implication in substitution urethroplasty.

[Morphology of collagen matrices for tissue engineering (biocompatibility, biodegradation, tissue response)].

OBJECTIVE: to perform a comparative morphological study of biocompatibility, biodegradation, and tissue response to implantation of collagen matrices (scaffolds) for tissue engineering in urology and other areas of medicine. MATERIAL AND METHODS: Nine matrix types, such as porous materials reconstructed from collagen solution; a collagen sponge-vicryl mesh composite; decellularized and freeze-dried bovine, equine, and fish dermis; small intestinal submucosa, decellularized bovine dura mater; and decellularized human femoral artery, were implanted subcutaneously in 225 rats. The tissues at the implantation site were investigated for a period of 5 to 90 days. Classical histology and nonlinear optical microscopy (NLOM) were applied. RESULTS: The investigations showed no rejection of all the collagen materials. The period of matrix bioresorption varied from 10 days for collagen sponges to 2 months for decellularized and freeze-dried vessels and vicryl meshes. Collagen was prone to macrophage resorption and enzymatic lysis, being replaced by granulation tissue and then fibrous tissue, followed by its involution. NLOM allowed the investigators to study the number, density, interposition, and spatial organization of collagen structures in the matrices and adjacent tissues, and their change over time during implantation. CONCLUSION: The performed investigation could recommend three matrices: hybrid collagen/vicryl composite; decellularized bovine dermis; and decellularized porcine small intestinal submucosa, which are most adequate for tissue engineering in urology. These and other collagen matrices may be used in different areas of regenerative medicine.

Submicron polyacrolein particles in situ embedded with upconversion nanoparticles for bioassay.

We report a new surface modification approach of upconversion nanoparticles (UCNPs) structured as inorganic hosts NaYF4 codoped with Yb(3+) and Er(3+) based on their encapsulation in a two-stage process of precipitation polymerization of acrolein under alkaline conditions in the presence of UCNPs. The use of tetramethylammonium hydroxide both as an initiator of acrolein polymerization and as an agent for UCNP hydrophilization made it possible to increase the polyacrolein yield up to 90%. This approach enabled the facile, lossless embedment of UCNPs into the polymer particles suitable for bioassay. These particles are readily dispersible in aqueous and physiological buffers, exhibiting excellent photoluminescence properties, chemical stability, and also allow the control of particle diameters. The feasibility of the as-produced photoluminescent polymer particles mean-sized 260 nm for in vivo optical whole-animal imaging was also demonstrated using a home-built epi-luminescence imaging system.

[Experimental validation of the developing a matrix based on decellularized vascular wall for subsequent substitution urethroplasty].

Urethral strictures are urgent urological problem. Anastomotic and substitution urethroplasty are the most effective treatments. For substitution urethroplasty, buccal mucosa is most often used. There are the following difficulties associated with the substitution urethroplasty: complications in the donor area, the lack of tissue for substitution, an additional incision, and increased timing of surgery due to the need to obtain a flap or graft. Tissue engineering can be useful in solving the above problems. Tissue engineering involves the use a matrix without cells and matrix with one or more types of cells (tissue-engineering designs). In our study we have evaluated the ability to create a matrix for the substitution urethroplasty in animal experiments. The decellularized cadaveric arterial wall was used as a matrix. Decellularization was performed using enzymatic method. At the first stage, we transplanted matrix fragments in interscapular region in rats. An extremely weak bioactivity dof decellularized matrix of cadaveric arterial wall (DMCAW) due to the low immunogenicity of the material was revealed. Thus resorption of DMCAW was quite slow (60-90 days). At the second stage, in an experiment on rabbits, substitution urethroplasty using tubular DMCAW was successfully performed. Intraoperative urethral defect up to 1.8 cm was created, which was replaced by a tubular DMCAW. The use of this type of matrix has showed good structural and functional results: urethral strictures did not arise, the rejection of the matrix was not observed. A slow degradation of the matrix and progressive epithelialization of onnective tissue capsule were revealed. Decellularized matrix based on cadaveric arterial wall can be considered as a material for substitution urethroplasty.

[The morphologic characteristics of scar tissues and the new clinicomorphologic classification of human skin scars].

The morphological study of 200 intraoperative biopsy specimens of skin scars of various etiology identified criteria for the differential diagnosis and mechanisms responsible for formation of 4 major types of scar tissues and their structural and functional varieties. In addition to the earlier known normotrophic, hypertrophic, and keloid scar tissues; the special type of scar tissue - the fibrously altered derma) was defined. Most skin scars were found to comprise a combination of a few of scar tissues and a relationship was established between the clinical type of a scar and its histological structure. The principles and mechanisms responsible for changes occurring in the structural composition of scars as the latter mature are described. The new scar clinicomorphological classification provides the basis for the pathogenetically substantiated choice of methods for the prevention and treatment of scars and for the prediction of recurrent scarring.