Tissue Engineering Technology Research Articles

The horizon of bone organoid: A perspective on construction and application.

Bone defects repair and regeneration by various causes such as tumor resection, trauma, degeneration, etc. have always been a key issue in the clinics. As one of the few organs that can regenerate after adulthood, bone itself has a strong regenerative ability. In recent decades, bone tissue engineering technology provides various types of functional scaffold materials and seed cells for bone regeneration and repair, which significantly accelerates the speed and quality of bone regeneration, and many clinical problems are gradually solved. However, the bone metabolism mechanism is complicated, the research duration is long and difficult, which significantly restricts the progress of bone regeneration and repair research. Organoids as a new concept, which is built in vitro with the help of tissue engineering technology based on biological theory, can simulate the complex biological functions of organs in vivo. Once proposed, it shows broad application prospects in the research of organ development, drug screening, mechanism study, and so on. As a complex and special organ, bone organoid construction itself is quite challenging. This review will introduce the characteristics of bone microenvironment, the concept of organoids, focus on the research progress of bone organoids, and propose the strategies for bone organoid construction, study direction, and application prospects.

Advances in tissue engineering technology for kidney regeneration and construction.

Tissue engineering is a highly interdisciplinary research field aiming at repairing, replacing, and regenerating the defective tissues. Over several decades of research, a variety of methods have been developed. The technical methods can be categorized into scaffold-based and scaffold-free strategies. In this mini review, the discussion will be focused on the technical methods of tissue engineering for kidney regeneration and construction.

Laser Assisted Bioprinting of laminin on biodegradable PLGA substrates: Effect on neural stem cell adhesion and differentiation

Laser Assisted Bioprinting (LAB) is recognized to be an enabling and versatile microfabrication technology for regenerative medicine and artificial tissue engineering. Current bioprinting concentrates on a layer-by-layer approach to print cells in consecutive stacks or nets, to recreate specialized tissue functions with a top-down approach. This synthering of proximal cells however reduces the long range correlation of tissue parenchyma and stroma given by natural development, as result of cells mobility and signaling. In this work, laminin, one of the main components of brain extracellular matrix is deposited by LAB on a biodegradable scaffold made of poly(lactic-co-glycolic acid) (PLGA), providing chemical cues for the adhesion and differentiation of neural stem cells NE-4C induced by retinoic acid. Surface roughness and LAB induced aggregates promote the initial adhesion of neuronal stem cells to the PLGA substrate and influence the formation of clusters and interconnection between them. The amount of laminin delivered inside the spot area may be controlled down to sub-monolayer coverage and a positive correlation between the laminin spots and soma of trafficking cells is demonstrated, also by computational modelling. Anisotropic orientation of neurite outgrowth is induced upon differentiation, up to 70% of processes protruding from stem cell clusters. The comparative analysis shows that the topological cue plays a major role in enhabling cluster formation on the scaffold, but the bioprinted laminin spots appear to be regulating the strength of connection between them, opening the way to control the functional morphology of artificial neural tissue constructs.

Application of biomaterials and tissue engineering in bladder regeneration.

The primary functions of the bladder are storing urine under low and stable pressure and micturition. Various forms of trauma, tumors, and iatrogenic injuries can cause the loss of or reduce bladder function or capacity. If such damage is not treated in time, it will eventually lead to kidney damage and can even be life-threatening in severe cases. The emergence of tissue engineering technology has led to the development of more possibilities for bladder repair and reconstruction, in which the selection of scaffolds is crucial. In recent years, a growing number of tissue-engineered bladder scaffolds have been constructed. Therefore, this paper will discuss the development of tissue-engineered bladder scaffolds and will further analyze the limitations of and challenges encountered in bladder reconstruction.

Applications of 3D Bioprinting Technology in Induced Pluripotent Stem Cells-Based Tissue Engineering.

Induced pluripotent stem cells (iPSCs) are essentially produced by the genetic reprogramming of adult cells. Moreover, iPSC technology prevents the genetic manipulation of embryos. Hence, with the ensured element of safety, they rarely cause ethical concerns when utilized in tissue engineering. Several cumulative outcomes have demonstrated the functional superiority and potency of iPSCs in advanced regenerative medicine. Recently, an emerging trend in 3D bioprinting technology has been a more comprehensive approach to iPSC-based tissue engineering. The principal aim of this review is to provide an understanding of the applications of 3D bioprinting in iPSC-based tissue engineering. This review discusses the generation of iPSCs based on their distinct purpose, divided into two categories: (1) undifferentiated iPSCs applied with 3D bioprinting; (2) differentiated iPSCs applied with 3D bioprinting. Their significant potential is analyzed. Lastly, various applications for engineering tissues and organs have been introduced and discussed in detail.

Pre-Clinical Study: Immunohistochemical evaluation of matrix metalloproteinase-13 on rabbit ( Oryctolagus cuniculus) socket healing after application of platelet-rich fibrin with and without hydroxyapatite.

Background: Tissue engineering technology has been used globally and proven to accelerate wound healing. This study aimed to analyse the effect of adding hydroxyapatite (HA) as a scaffold to platelet-rich fibrin (PRF) as a growth factor in accelerating the wound healing process as seen from the expression of matrix metalloproteinase-13 (MMP-13). Methods: This research is an animal experiment conducted on 18 rabbits ( Oryctolagus cuniculus). Rabbits were randomly divided into the following three groups of treatment: (G1) the application of PRF group, (G2) the application of PRF+HA group and (C) the control group without any application. Furthermore, each treatment group was split randomly into three groups of observation time. Periodontal tissue biopsy was performed to analyse the histopathological features that were examined on the basis of the level of MMP-13 immunoexpression. Results: MMP-13 immunoexpression in the PRF+HA group showed better histoscore results, indicating a substantial reduction in MMP-13 values compared with other groups. The healing process was shown to increase with increasing observation time (p<0.05), and the PRF+HA group outperformed the PRF and control groups. On day 3, MMP-13 exhibited a dark brown colour of Immunohistochemistry (IHC), which indicated an increase in the expression value of MMP-13 in the early stages of healing, namely, inflammation. On day 14, light brown IHC was seen, especially in group 2, as a reference that the remodeling process had begun. Conclusions: This study indicates that the application of HA can accelerate the socket healing process by decreasing the level of immunoexpression of MMP-13. HA is an alloplastic material that has inherent bioactive properties that support osteoconduction, which functions as a scaffold in the form of a fibrin matrix that can bind MMPs so that it can accelerate the wound healing process.

Tissue engineering and cell technologies: how these can help in correction of urinary system pathologies. Literature review and own experience

SummaryIntroduction. Modern possibilities of cellular and tissue engineering technologies are presented in this pub-lication, that are developed to be applied to urologic patholo gies in experimental and clinical practice. Оwn experience is described in rabbit bladder reconstruction with tissue engineering construction. Тissue engineering is one of the leading trends in modern science and envis-ages the development of restoration or replacement tech-niques for damaged structures with the use of scaffolds and cells. However, in spite of a huge number of publica-tions, urologic structures reconstructions are in minority. Nowadays, to treat damaged human tissues and organs, bioresorbable synthetic polimers are becoming more and more popular, those are used as the basis for cell culture (Ho M.H. et al., 2006; Shao J. et al., 2012). Foreign scien-tists have been successfully attempting to create tissue wall analogues for a long time. Маterials and methods.15 male Chinchilla rabbits underwent partial bladder resection with scaffold grafting containing smooth mio-cytes with urothelium, fibroblasts and mesenchymal stem cells, as well as acellular matrix. Results. In the group of animals that received scaffoled with labelled mesenchy-mal stem cells, in 5 out of 6 cases, matrix lysis occurred with no signs of graft rejection. After 2.5 months post-op, the capacity of the bladders was comparable with that pre-op. In the implantation site, one could visually see the area of a newly formed bladder wall, with vasculariza-tion signs. Histologically, initial stages of reparation and angiogenesis have been identified. Confocal microscopy of cryoslices from the implantation site showed labelled cells taking part in the urothelium-like structure forma-tion. In all cases when acellular matrix or scaffolds with smooth miocytes with urothelium and fibro blasts were implanted, graft rejection took place, with various de-grees of inflammation and decrease of bladder capacity. Conclusion. The use of tissue engineering construction made of composite matrix and rabbit mesenchymal stem cells was effective for small bladder defects reconstruc-tion. Further development of techniques to create mul-ticomponent graft with allogenic cells may improve the results of treating such pathologies in patients when au-togenic material cannot be harvested. A study is under way in St Petersburg Research Institute of Phthisiopulm-onology as of now, to study tissue engineered bladder augmentation, up to its total replacement (Russian Scien-tific Foundation grant no. 22-25-20167, https://rscf.ru/project/22-25-20167/ and St Petersburg Scientific Foun-dation grant in accordance with agreement dd. 14th April 2022 no. 20/2022)

Advanced Robotics to Address the Translational Gap in Tendon Engineering.

Tendon disease is a significant and growing burden to healthcare systems. One strategy to address this challenge is tissue engineering. A widely held view in this field is that mechanical stimulation provided to constructs should replicate the mechanical environment of native tissue as closely as possible. We review recent tendon tissue engineering studies in this article and highlight limitations of conventional uniaxial tensile bioreactors used in current literature. Advanced robotic platforms such as musculoskeletal humanoid robots and soft robotic actuators are promising technologies which may help address translational gaps in tendon tissue engineering. We suggest the proposed benefits of these technologies and identify recent studies which have worked to implement these technologies in tissue engineering. Lastly, key challenges to address in adapting these robotic technologies and proposed future research directions for tendon tissue engineering are discussed.

Use of ozone on regeneration of 3D critical size bone defects

Extensive bone loss is often experienced in the treatment of trauma, tumors, infections, congenital diseases, and disuse. Autologous bone grafting is considered the gold standard for solving these demands due to its osteogenic, osteoinductive, and osteoconductive characteristics. Thus, the need more surgical sites, volumetric limitations, risk of infections, and in some situations, the cost of hospitalization should be considered. 3D printing biomanufatured calcium phosphate-based scaffolds raises as osteoconductive materials for bone reconstructions. Volumetric disposability, biocompatible performance and easy handling are some benefits of these new options. Advances in biology and tissue engineering technologies are making it possible to use materials and techniques together to achieve better results. Osteogenic properties of ozone are being mapped which make this material a possible biofunctionalizer 3D scaffolds and other materials for tissue engineering. Thus, deficiencies such as the osteogenic potential and remodeling ability of the scaffolds still remains as limitations. Ozone therapy has been used as adjuvant in regeneration and repair processes by releasing free oxygen and increasing the responsiveness of cellular metabolism and generation of vital energy. Therefore, the release responses of inflammatory mediators, growth factors, and cytokines become more effective, especially in situations in which they are deficient, such as at advanced ages. The objective of this literature review is to evaluate the role of ozone therapy to optimize cellular response for the local response of bone formation at critical size defect sites reconstructed with 3D biomanufacturing scaffolds.

Cellular Interaction of Human Skin Cells towards Natural Bioink via 3D-Bioprinting Technologies for Chronic Wound: A Comprehensive Review.

Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to contraction and scarring formation. Besides, donor sites for full-thickness skin grafts are very limited if the wound area is big, and it has been proven to have the lowest survival rate compared to thick- and thin-split thickness. Tissue engineering technology has introduced new advanced strategies since the last decades to fabricate the composite scaffold via the 3D-bioprinting approach as a tissue replacement strategy. Considering the current global donor shortage for autologous split-thickness skin graft (ASSG), skin 3D-bioprinting has emerged as a potential alternative to replace the ASSG treatment. The three-dimensional (3D)-bioprinting technique yields scaffold fabrication with the combination of biomaterials and cells to form bioinks. Thus, the essential key factor for success in 3D-bioprinting is selecting and developing suitable bioinks to maintain the mechanisms of cellular activity. This crucial stage is vital to mimic the native extracellular matrix (ECM) for the sustainability of cell viability before tissue regeneration. This comprehensive review outlined the application of the 3D-bioprinting technique to develop skin tissue regeneration. The cell viability of human skin cells, dermal fibroblasts (DFs), and keratinocytes (KCs) during in vitro testing has been further discussed prior to in vivo application. It is essential to ensure the printed tissue/organ constantly allows cellular activities, including cell proliferation rate and migration capacity. Therefore, 3D-bioprinting plays a vital role in developing a complex skin tissue structure for tissue replacement approach in future precision medicine.

Cutting-edge tissue engineering strategies for cultured meat

As an emerging cellular agriculture technology, cell cultured meat aims to produce meat from in vitro cell culture instead of conventional livestock slaughtering. Various tissue engineering technologies have been applied for cell cultured meat. In this perspective, we will overview the cutting-edge tissue engineering strategies for cell cultured meat from the classifications of textured scaffolds, 3D bioprinting, molding, patterning, and cell sheet engineering, and introduce the applied materials as well. The future prospects and challenges will be discussed in the end.

Waste-derived biomaterials as building blocks in the biomedical field.

Recent developments in the biomedical arena have led to the fabrication of innovative biomaterials by utilizing bioactive molecules obtained from biological wastes released from fruit and beverage processing industries, and fish, meat, and poultry industries. These biological wastes that end up in water bodies as well as in landfills are an affluent source of animal- and plant-derived proteins, bio ceramics and polysaccharides such as collagens, gelatins, chitins, chitosans, eggshell membrane proteins, hydroxyapatites, celluloses, and pectins. These bioactive molecules have been intricately designed into scaffolds and dressing materials by utilizing advanced technologies for drug delivery, tissue engineering, and wound healing relevance. These biomaterials are environment-friendly, biodegradable, and biocompatible, and show excellent tissue regeneration attributes. Additionally, being cost-effective they can reduce the burden on the healthcare system as well as provide a sustainable solution to waste management. In this review, the current trends in the utilization of plant and animal waste-derived biomaterials in various biomedical fields are considered along with a separate section on their applications as xenografts.

Fabrication of Micropatterned Fish Scale Collagen Scaffold Using Microelectromechanical Systems Technologies for Oral Mucosa Tissue Engineering

Fabrication of Micropatterned Fish Scale Collagen Scaffold Using Microelectromechanical Systems Technologies for Oral Mucosa Tissue Engineering

Application and development of 3D bioprinting in cartilage tissue engineering.

Articular cartilage defects are one of the most common clinical diseases of bone articulation. Early repair of damaged joint cartilage can effectively stop the progression of arthritis and restore health to the patient. In recent years, various therapeutic strategies have been developed to repair cartilage defects and make them available for clinical transplantation. However, cartilage defect repair remains a clinically unsolved challenge to date. Although there have been numerous breakthroughs in cartilage defect repair, the limited spatial complexity of tissue-engineered implants in terms of cells, materials, and active factors has limited the success of engineered cartilage so far. Bioprinting technology allows for the construction of three-dimensional tissues drop by drop and layer by layer, where cells, matrices, and active materials can be deposited on demand while maintaining high precision. Therefore, adopting the bioprinting technology in cartilage tissue engineering promises to develop the next generation of engineered cartilage and address the cartilage defect/regeneration problem. In this paper, we reviewed the bioinks and bioprinting technologies used in cartilage tissue engineering, outlined the recent advances of 3D bioprinting technologies in cartilage tissue engineering, and prospected the development direction of next-generation engineered cartilage.

Photo-crosslinkable methacrylated konjac glucomannan (KGMMA) hydrogels as a promising bioink for 3D bioprinting.

Three-dimensional (3D) bioink with favorable printability, strength, and biocompatibility challenged the 3D bioprinting technology in cartilage tissue engineering. Herein, we innovatively fabricated photo-crosslinkable methacrylated konjac glucomannan (KGMMA) as a novel biomaterial ink for 3D extrusion bioprinting in an attempt to construct precisely patterned tissues. Specifically, konjac glucomannan (KGM) was modified by methacrylic anhydride, which is a kind of photoreactive group, to form KGMMA. After UV crosslinking, the printed KGMMA hydrogel formed a covalent crosslinking network with high strength, desired shearing, and swelling and degradation characteristics. The properties of the KGMMA hydrogel could be modulated by changing the contents of MA. The shear-thinning property of the KGMMA biomaterial ink enables excellent printability, which can print different shapes including lattices, hexagons, and flowers. Furthermore, the bioinks support cell growth after being printed with chondrocytes for a culture. Therefore, the biodegradable, injectable, and photo-crosslinkable KGMMA biomaterial ink holds a great promise for cartilage tissue engineering.

Carbon Footprint of 3D-Printed Bone Tissue Engineering Scaffolds: An Life Cycle Assessment Study

The bone tissue engineering scaffolds is one of the methods for repairing bone defects caused by various factors. According to modern tissue engineering technology, three-dimensional (3D) printing technology for bone tissue engineering provides a temporary basis for the creation of biological replacements. Through the generated 3D bone tissue engineering scaffolds from previous studies, the assessment to evaluate the environmental impact has shown less attention in research. Therefore, this paper is aimed to propose the Model of life cycle assessment (LCA) for 3D bone tissue engineering scaffolds of 3D gel-printing technology and presented the analysis technique of LCA from cradle-to-gate for assessing the environmental impacts of carbon footprint. Acrylamide (C3H5NO), citric acid (C6H8O7), N,N-Dimethylaminopropyl acrylamide (C8H16N2O), deionized water (H2O), and 2-Hydroxyethyl acrylate (C5H8O3) was selected as the material resources. Meanwhile, the 3D gel-printing technology was used as the manufacturing processes in the system boundary. The analysis is based on the LCA Model through the application of GaBi software. The environmental impact was assessed in the 3D gel-printing technology and it was obtained that the system shows the environmental impact of global warming potential (GWP). All of the emissions contributed to GWP have been identified such as emissions to air, freshwater, seawater, and industrial soil. The aggregation of GWP result in the stage of manufacturing process for input and output data contributed 47.6% and 32.5% respectively. Hence, the data analysis of the results is expected to use for improving the performance at the material and manufacturing process of the product life cycle.

Introduction of Innovative Tissue Engineering Technologies into Medical Practice to Restore Damaged Joints

We analyzed the results of surgical treatment of 10 patients with II and III degree osteoarthritis of the knee joint, men = 3, women = 7. The average age was 49.3 years (±28). An arthroscopic revision of the knee joint was performed to determine the location, size and depth of cartilage defects. The synovial membrane was taken (30-50 mg), autologous mesenchymal stem cells were isolated and cultured. Next, arthroscopy of the knee joint was performed, where a heparin-conjugated fibrin hydrogel was implanted into the defect area, containing mesenchymal stem cells of the synovial membrane and growth factors transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein 4 (BMP-4).None of the patients, heparin-conjugated fibrin hydrogel with mesenchymal stem cells and growth factors caused serious undesirable complications after implantation into articular cartilage defects, which may indicate the safety of the hydrogel.Key words: mesenchymal stem cells, synovia, osteoarthrosis, cell therapy, heparin-conjuged fibrin hydrogel.

A narrative review of current therapies in unilateral recurrent laryngeal nerve injury caused by thyroid surgery.

To summarize and compare current common treatments in recurrent laryngeal nerve injury (RLNI). In addition, we introduced nerve tissue engineering technology in RLNI animal models. This review is a comprehensive summary of current therapies for unilateral RLNI. RLNI is a common complication in thyroid surgery. Although preoperative imaging and intraoperative nerve monitoring are widely applied, some damage to nerves is still inevitable. Currently, advances in nerve repair and regeneration have been made, but relatively few studies have focused on RLNI. In this review, we summarized and compared current common treatments in RLNI. We searched the literature on PubMed and Web of Science, and chose studies about RLNI in thyroid surgery. Keywords included the following terms: "recurrent laryngeal nerve regeneration", "injection laryngoplasty", "type I thyroplasty", "arytenoid adduction", and "nerve tissue engineering technology". Only English language studies were included. In the section on nerve tissue engineering technology, we described the application in detail in the table below. Currently, the majority of treatments could obtain different effects to some extent, but there are still shortcomings that need to be overcome further overcome. Therefore, potential exploration such as nerve tissue engineering technology is worthy of attention.

Development of theoretical model expressing self-beating deformation behaviour of human iPS cardiomyocytes tube

In recent years, a regenerative therapy method using human iPS cell-derived myocardial cells (hiPS-CM) has attracted attention. In the future, large-scale myocardial three-dimensional structures that apply tissue engineering technology are expected. In this study, we developed a three-dimensional structure with a pump function by the self-beating power of hiPS-CM. Then, the deformation behavior of the 3D hiPS-CM structure associated with self-pulsation was examined. The pulsatile behavior of hiPS-CM was quantitatively evaluated by using a high-speed optical measurement system with the digital image correlation method. Then, the experimental strain data was used to construct the stress-strain response with use of a theoretical active stress model originally developed by Guccione et al. A theoretical constitutive model was also developed by combining the Guccione's active stress model and the viscoelastic Maxwell model. As a result, this theoretical model stress-strain behavior showed a good agreement with the combination model of experimental strain and theoretical stress.

Autologous blood derived cell therapy in maxillofacial bone graft surgery.

Tissue regeneration is one of the ultimate goals of maxillofacial surgery and various types of tissue engineering technologies have been utilized in clinics. Healthy resources of host cells and growth factors are essential for the tissue engineering, therefore autologous blood-derived cell therapy was introduced. In this article, clinical applications of the autologous platelet concentrates and stem cell separation therapy will be summarized and evaluated for their efficacy and feasibility in the current maxillofacial clinics.