Cardiac tissue engineering: effects of bioreactor flow environment on tissue constructs

The limited ability of cardiac muscle to regenerate after injury and the small number of organs available for transplantation motivate studies aimed at curative treatment options. Tissue engineering based on the integrated use of cells on biomaterial scaffolds in bioreactors may offer cardiac grafts suitable for surgical attachment to the myocardium or for basic research. In one of the current approaches, neonatal rat cardiomyocytes are combined with collagen sponges, gels or polyglycolic acid scaffolds (PGA). Cultivations performed in dishes, static or mixed flasks or rotating bioreactors yield constructs with a thin (100–200 µm) peripheral layer of tissue expressing markers of cardiac differentiation and able to propagate electrical signals. The non‐uniform cell distribution is a result of oxygen diffusional limitations within the constructs. Cultivations with perfusion of culture medium through the construct enhance the convective‐diffusive oxygen supply and yield 1–2 mm thick constructs with physiologically high and spatially uniform distribution of viable cells expressing cardiac markers. We review here a series of studies we conducted using cells seeded on three‐dimensional scaffolds and cultured in several different bioreactors, to demonstrate that the bioreactor flow environment can have substantial effects on structural and functional properties of cardiac constructs. Copyright © 2006 Society of Chemical Industry     

Strategies for non‐invasive imaging of polymeric biomaterial in vascular tissue engineering and regenerative medicine using ultrasound and photoacoustic techniques

The ability of new polymeric materials to provide excellent biomechanical properties expanded their potential for biomedical applications enormously. The use of non‐invasive imaging modalities could provide crucial information to monitor the efficacy/effectiveness/efficiency of the new materials employed in ‘regenerative’ approaches, including scaffolds, hydrogels, self‐assembling materials and nanosized structures. The assessment of the morpho‐functional and metabolic changes of treated or implanted tissues, the visualization of sites of drug delivery and the real‐time check of the in vivo efficacy of therapeutics could be achieved by non‐invasive micro‐ and macro‐imaging techniques. The macro‐ and nano‐requirements of these new materials and their behaviour in vivo can be investigated using standard approaches such as computed tomography, MRI and ultrasound techniques and the emerging photoacoustic imaging. This paper presents recent advancements of ultrasonography and the novel photoacoustic technique to monitor the morpho‐functional parameters of synthetic polymeric scaffolds and conduits in experimental models. © 2016 Society of Chemical Industry     

The incorporation and controlled release of platelet‐rich plasma‐derived biomolecules from polymeric tissue engineering scaffolds

Platelet‐rich plasma (PRP) has been gaining popularity in recent years as a cost‐effective material capable of stimulating healing in a number of different clinical applications. As the clinical role of PRP has been growing so too has its prevalence in the fields of tissue engineering and regenerative medicine, particularly in the field of extracellular matrix (ECM) analogue scaffold fabrication. As polymeric scaffold fabrication techniques strive to create structures that ever more closely replicate the native ECM's form and function, the need for increased scaffold bioactivity becomes more pronounced. PRP, which has been shown to contain over 300 bioactive molecules, has the potential to deliver a combination of growth factors and cytokines capable of stimulating cellular activity through enhanced chemotaxis, proliferation and ECM production. The ability to incorporate such a potent bioactive milieu into a polymeric tissue engineering scaffold, which lacks intrinsic cell signaling molecules, may help to promote scaffold integration with native tissues and increase the overall patency of polymeric ECM analogue structures. This mini‐review briefly discusses the physiological basis of PRP and its current clinical use, as well as the potential role that PRP may play in the future of polymeric tissue engineering scaffold design. Copyright © 2012 Society of Chemical Industry     

Polymers for medical and tissue engineering applications

Recent decades have seen great advancements in medical research into materials, both natural and synthetic, that facilitate the repair and regeneration of compromised tissues through the delivery and support of cells and/or biomolecules. Biocompatible polymeric materials have become the most heavily investigated materials used for such purposes. Naturally‐occurring and synthetic polymers, including their various composites and blends, have been successful in a range of medical applications, proving to be particularly suitable for tissue engineering (TE) approaches. The increasing advances in polymeric biomaterial research combined with the developments in manufacturing techniques have expanded capabilities in tissue engineering and other medical applications of these materials. This review will present an overview of the major classes of polymeric biomaterials, highlight their key properties, advantages, limitations and discuss their applications. © 2014 Society of Chemical Industry     

Synthesis and degradation of agar‐carbomer based hydrogels for tissue engineering applications

Hydrogels studied in this investigation, synthesized starting from agarose and Carbomer 974P, were chosen for their potential use in tissue engineering. The strong ability of hydrogels to mimic living tissues should be complemented with optimized degradation time profiles: a critical property for biomaterials but essential for the integration with target tissue. In this study, chosen hydrogels were characterized both from a rheological and a structural point of view before studying the chemistry of their degradation, which was performed by several analysis: infrared bond response [Fourier transform infrared (FT‐IR)], calorimetry [differential scanning Calorimetry (DSC)], and % mass loss. Degradation behaviors of Agar‐Carbomer hydrogels with different degrees of crosslinkers were evaluated monitoring peak shifts and thermal property changes. It was found that the amount of crosslinks heavily affect the time and the magnitude related to the process. The results indicate that the degradation rates of Agar‐Carbomer hydrogels can be controlled and tuned to adapt the hydrogel degradation kinetics for different cell housing and drug delivery applications. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and characterization of novel chitosan/nanodiopside/nanohydroxyapatite composite scaffolds for tissue engineering applications

Chitosan/nanodiopside/nanohydroxyapatite (CS/nDP/nHAp) composite scaffolds were prepared from the mixture of chitosan, nDP, and nHAp in different inorganic/organic weight ratios by using the freeze-drying method. The prepared nHAp and composite scaffolds were investigated using BET, TG, FT-IR, SEM, EDS, and XRD techniques. The composite scaffolds had 50–85% porosities with interlinked porous networks. Moreover, investigation of the cell proliferation, adhesion, and viability using MTT test, and mouse preosteoblast cell proved the cytocompatibile nature of the composite scaffolds with improved cell attachment and proliferation. All these results essentially illustrated that this composite could be a potential for bone tissue engineering applications.     

纳米纤维应用于组织工程的研究进展

组织工程支架的关键作用是起到引导细胞繁殖、生长,促进组织修复的一个过程。纳米纤维支架由于具有特殊的纳米效应,而更有利于细胞的黏附、增殖、功能化,因而被广泛应用于组织工程。本文分别介绍了纳米纤维支架在各类组织工程中应用,包括皮肤和创伤敷料组织工程、血管组织工程、神经组织工程、骨组织工程、软骨组织工程中应用的研究进展,同时介绍了纳米纤维支架药物控制释放中的应用。指出目前纳米技术还不成熟,需要从制备工艺的优化、基因工程的引入及纳米材料安全性能的科学评价等几方面解决纳米纤维支架在组织修复工程中面临的问题。     

Cryo-copolymerization preparation of dextran-hyaluronate based supermacroporous cryogel scaffolds for tissue engineering applications

Dextran-hyaluronate (Dex-HA) based supermacroporous cryogel scaffolds for soft tissue engineering were prepared by free radical cryo-copolymerization of aqueous solutions containing the dextran methacrylate (Dex-MA) and hyaluronate methacrylate (HA-MA) at various macromonomer concentrations under the freezing condition. It was observed that the suitable total concentration of macromonomers for the preparation of Dex-HA cryogel scaffold with satisfied properties was 5% (w/w) at the HA-MA concentration of 1% (w/v), which was then used to produce the test scaffold. The obtained cryogel scaffold with 5% (w/w) macromonomer solution had high water permeability (5.1 × 10^-12 m²) and high porosity (92.4%). The pore diameter examined by scanning electron microscopy (SEM) was in a broad range of 50–135 μm with the mean pore diameter of 91 μm. Furthermore, the cryogel scaffold also had good elastic nature with the elastic modulus of 17.47±1.44 kPa. The culture of 3T3-L1 preadipocyte within the scaffold was investigated and observed by SEM. Cells clustered on the pore walls and grew inside the scaffold indicating the Dex-HA cryogel scaffold could be a promising porous biomaterial for applications in tissue engineering.     

Hierarchical bioceramic scaffold for tissue engineering: A review

Bioceramic scaffolds have a promising application in bone-tissue engineering field. However, bioceramic scaffolds exhibit low fracture toughness; hence, to overcome this problem, hierarchical bioceramic scaffold or bioceramic scaffolds coated with polymer are produced. Starting with the fundamental requirements for bioceramic scaffold, this article provides detailed information on recent developments of method to produce porous bioceramics scaffold and hierarchical bioceramic scaffold. Chemical modifications to enhance interfacial adhesion and formation of interpenetrating network structures between the bioceramic scaffold and the natural polymer layer are discussed in this article. Areas of future research are highlighted at the end of this review.     

组织工程支架材料及制备方法研究现状

组织工程支架已经广泛应用于皮肤、软骨、心血管、心脏等各种组织的修复中.组织工程材料分为天然材料和合成材料两大类,均需要具备良好的生物相容性.组织工程支架的制备方法主要有相分离、冷冻干燥、发泡、颗粒浸出、静电纺丝、3D打印等.现对组织工程支架所用到的材料、制备方法以及组织工程支架的应用进行综述.     

Technology of electrostatic spinning for the production of polyurethane tissue engineering scaffolds

Electrostatic spinning was investigated as an alternative to electrospinning to establish the potential of the technique for the production of a range of microfibrous polyurethane scaffolds with a variety of structures and properties related to the fabrication conditions. Tecoflex^® SG‐80A polyurethane was spun, systematically altering the spinning parameters, and the resulting scaffolds were characterised using scanning electron microscopy. Inter‐fibre separation was significantly affected by flow rate, spray distance and grid and mandrel voltages; fibre diameter by flow rate and mandrel voltage; void fraction by flow rate; fibre orientation by traverse speed and mandrel speed; and thickness by flow rate. Thus, scaffold (three‐dimensional) architecture may be controlled through manipulation of the electric fields and the fibre deposition (spinning parameters of flow rate and grid and mandrel voltages); and by spray movement and direction (spinning parameters of relative spray height, spray distance, traverse speed and mandrel speed). There were significant differences between the internal and external scaffold surfaces, due in part to the manner in which the surface of the mandrels was prepared. We conclude that the process may be used to produce a range of polyurethane scaffolds for use in many tissue engineering applications. Copyright © 2007 Society of Chemical Industry     

Biomimetic porous collagen/hydroxyapatite scaffold for bone tissue engineering

Bone defect and osteochondral injury frequently occur due to diseases or traumatism and bring a crucial challenge in orthopedics. The hybrid scaffold has shown promise as a potential strategy for the treatment of such defects. In this study, a novel biomimetic porous collagen (Col)/hydroxyapatite (HA) scaffold was fabricated through assembling layers of Col containing gradual amount of HA under the assistance of “iterative layering” freeze‐drying process. The scaffold presents a double gradient of highly interconnected porosity and HA content from top to bottom, mimicking the inherent physiological structure of bone. Owing to the biomimetic structure and component, significant increase of cell proliferation, alkaline phosphatase activity, and osteogenic differentiation in vitro was observed, illustrating potential application of the excellent Col/HA scaffold as a promising strategy for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45271.     

Biomimetic protein‐based elastomeric hydrogels for biomedical applications

In recent years, protein‐based elastomeric hydrogels have gained increased research interest in biomedical applications for their remarkable self‐assembly behaviour, tunable 3D porous structure, high resilience (elasticity), fatigue lifetime (durability), water uptake, excellent biocompatibility and biological activity. The proteins and polypeptides can be derived naturally (animal or insect sources) or by recombinant (bacterial expression) routes and can be crosslinked via physical or chemical approaches to obtain elastomeric hydrogels. Here we review and present the recent accomplishments in the synthesis, fabrication and biomedical applications of protein‐based elastomeric hydrogels such as elastin, resilin, flagelliform spider silk and their derivatives. © 2013 Society of Chemical Industry     

Evaluation of PCL/chitosan electrospun nanofibers for liver tissue engineering

In this investigation, a nanofibrous scaffold was fabricated through electrospinning of polycaprolactone (PCL) and chitosan (CS) using a novel collector to make better orientation and pore size for cell infiltration. PCL/CS nanofibers with 90-rpm collector speed and 40° angle between collector wires of the new collector have fewer diameters with better pore, size and nanofibers orientation. Mechanical properties, roughness parameters, topology, structure, hydrophilicity, and cell growing were considered for liver tissue engineering. The cell culture was done using epithelial liver mouse cells. The developed electrospun PCL/CS scaffold using novel collector would be an excellent matrix for biomedical applications especially liver tissue engineering.     

Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges

Recently, poly (?-caprolactone) (PCL) has gained a lot of attention, and shown great potential in biomedical applications. Among synthetic polymers, PCL is one of the easiest to process and manipulate into a large range of shapes and sizes due to its low melting temperature and its superior viscoelastic properties. In this review article the authors focus mainly on the properties of PCL-based biomaterials relevant to drug delivery and tissue engineering applications. The authors provide an insight into the recent developments and challenges of PCL-based biomaterials as a critical component of new therapeutic strategies for many diseases.     

Extracellular matrix regenerated: tissue engineering via electrospun biomimetic nanofibers

While electrospinning had seen intermittent use in the textile industry from the early twentieth century, it took the explosion of the field of tissue engineering, and its pursuit of biomimetic extracellular matrix (ECM) structures, to create an electrospinning renaissance. Over the past decade, a growing number of researchers in the tissue engineering community have embraced electrospinning as a polymer processing technique that effectively and routinely produces non‐woven structures of nanoscale fibers (sizes of 80 nm to 1.5 µm). These nanofibers are of physiological significance as they closely resemble the structure and size scale of the native ECM (fiber diameters of 50 to 500 nm). Attempts to replicate the many roles of native ECM have led to the electrospinning of a wide array of polymers, both synthetic (poly(glycolic acid), poly(lactic acid), polydioxanone, polycaprolactone, etc.) and natural (collagen, fibrinogen, elastin, etc.) in origin, for a multitude of different tissue applications. With various compositions, fiber dimensions and fiber orientations, the biological, chemical and mechanical properties of the electrospun materials can be tailored. In this review we highlight the role of electrospinning in the engineering of different tissues and applications (skin/wound healing, cartilage, bone, vascular tissue, urological tissues, nerve, and ligament), and discuss its potential role in future work. Copyright © 2007 Society of Chemical Industry     

Chitin scaffolds in tissue engineering

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.     

A novel strategy for cartilage tissue engineering: Collagenase-loaded cryogel scaffolds in a sheep model

In this study, we developed a novel strategy, through which cartilage tissue pieces were placed in a sheep cartilage defect model and covered with a collagenase incorporated cryogel scaffold (in vivo cartilage tissue engineering, IVCTE group). While applying this strategy, the chondrocytes could be isolated inside the body and the treatment could be accomplished in one session. To compare our strategy, to another group, in which we used cultured cells and Chondro-gide, standard matrix-induced autologous chondrocyte implantation (MACI) was applied. Although the MACI applied group demonstrated better healing than IVCTE, the type II collagen synthesis was better in the IVCTE group compared to MACI applied group. Collagenase did not have detrimental effect on surrounding cartilage in IVCTE group. The preliminary results of the novel strategy applied group (IVCTE) were promising.     

Preparation and characterization of novel chitosan/zeolite scaffolds for bone tissue engineering applications

In this study, chitosan-based novel scaffolds containing zeolite A were fabricated by freeze-drying technique. The nanocomposite scaffolds were prepared from chitosan and zeolite A nanocrystals with different amounts (0.5, 1.0, and 2.0%) in aqueous media. The zeolite A nanocrystals and nanocomposite scaffolds were characterized by using FTIR, X-ray powder diffraction, scanning electron microscope, and thermogravimetric analysis. The scaffolds were seeded with bone marrow-derived human mesenchymal stem cell line (UE7T-13), and cell attachment, viability, and cytotoxicity assays were performed. In vitro cytotoxicity of scaffolds toward human mesenchymal stem cell line was evaluated through the evaluation of cell viability and cell attachment assays.     

Fabrication and evaluation of nanofibrous polyhydroxybutyrate valerate scaffolds containing hydroxyapatite particles for bone tissue engineering

Tissue engineering is a new approach for regeneration of damaged tissues. The current clinical methods such as autograft and allograft transplantation are not effective for repairing bone damages, mainly due to the limited available sources and the donor-site side effects. In this research, the nanocomposite poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/nano hydroxyapatite (nHA) scaffolds with different nHA ratios for bone regeneration were utilized. The diameter and porosity of scaffolds were approximately 200?nm and 74%, respectively. The degradability test of the scaffolds suggests a low degradation rate with total degradation of 30% after 3 months. Cytotoxicity result showed that cultured osteoblast cells (MC3T3) on nanocomposite scaffolds had superiority in terms of higher proliferation and attachment in comparison with PHBV scaffold. The protein expression of alkaline phosphatase illustrated that nanofibrous scaffold containing hydroxyapatite had the highest alkaline phosphatase activities as a result of better proliferation. These results recommend that PHBV/nHA scaffolds are suitable candidates for bone tissue engineering.