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Calcification of bioprosthetics is a primary challenge in the field of artificial heart valves and a main reason for biological heart valve prostheses failure. Recent advances in nanomaterial science have promoted the development of polymers with advantageous properties that are likely suitable for artificial heart valves. In this work, we developed a nanocomposite polymeric biomaterial POSS-PEG (polyhedral oligomeric silsesquioxane-polyethylene glycol) hybrid hydrogel, which not only has improved mechanical and surface properties but also excellent biocompatibility. The results of atomic force microscopy and in vivo animal experiments indicated that the content of POSS in the PEG matrix plays an important role on the surface and contributes to its biological properties, compared to the decellularized porcine aortic valve scaffold. Additionally, this modification leads to enhanced protection of the hydrogel from thrombosis. Furthermore, the introduction of POSS nanoparticles also gives the hydrogel a better calcification resistance efficacy, which was confirmed through in vitro tests and animal experiments. These findings indicate that POSS-PEG hybrid hydrogel is a potential material for functional heart valve prosthetics, and the use of POSS nanocomposites in artificial valves may offer potential long-term performance and durability advantages.

Previous studies have proved that fibrin is an excellent scaffold material for tissue engineered blood vessel. However, the mechanical properties of fibrin are not enough. One way to solve the problem is to combine polymer materials with fibrin to enhance its biomechanical properties. In this study, a novel polycaprolactone (PCL)/fibrin composite scaffold was prepared by electrospinning technology. The morphological, physicochemical analysis, blood compatibility, biomechanical properties, biocompatibility and biodegradability of this vascular scaffold were evaluated. The results showed that electrospun PCL/fibrin scaffold possessed smaller aperture and larger fiber diameter than that of fibrin scaffold. The swelling ratio of the vascular PCL/fibrin scaffold at (0:100), (10:90), (20:80) and (30:70) was 112 ± 5.3, 103 ± 6.9, 94 ± 5.9 and 89 ± 3.4%, respectively. Mechanical properties of fibrin scaffolds were enhanced significantly by the addition of PCL. Furthermore, the time of plasma re-calcification, activated partial thromboplastin time and thromboplastin time in four different proportions of PCL/fibrin scaffolds were similar to that of the control group. Degradation experiments

Three-dimensional biodegradable porous scaffolds play an important role in tissue engineering. The degradable scaffold material, based on 1,4-butanediamine-modified poly(lactide-co-glycolide) (BMPL...

Decellularized extracellular matrix (dECM) is widely used in regenerative medicine as a scaffold material due to its unique biological activity and good biocompatibility. Hydrogel is a three-dimensional network structure polymer with high water content and high swelling that can simulate the water environment of human tissues, has good biocompatibility, and can exchange nutrients, oxygen, and waste with cells. At present, hydrogel is the ideal biological material for tissue engineering. In recent years, rapid development of the hydrogel theory and technology and progress in the use of dECM to form hydrogels have attracted considerable attention to dECM hydrogels as an innovative method for tissue engineering and regenerative medicine. This article introduces the classification of hydrogels, and focuses on the history and formation of dECM hydrogels, the source of dECM, the application of dECM hydrogels in tissue engineering and the commercial application of dECM materials.

Tissue engineering advancements have seen a multitude of findings in several disciplines, including cell biology, imaging, characterization of cell–material and cell–cell interactions, and also novel biomaterial research. The main aim of tissue engineering, however, remains as a tool to restore, maintain, or improve defective tissue functions. The paradigm of this concept is threefold: (1) Isolation of cells, (2) Seeding of cells into the appropriate 3D scaffolds, and (3) Providing the appropriate growth factors and physical and mechanical conditions in-vitro thereby mimicking the native conditions conducive for cell and tissue growth. The development of the 3D scaffold or matrix is by far the most challenging aspect wherein the choice of the scaffold material, its biocompatibility, cell–material interactions, its biodegradation and bioresorption properties, all play a major role. Polymers have been a mainstay as scaffold material for such applications. Both synthetic and natural polymers have been used as matrices for cell and tissue growth. The main aim in development of polymeric scaffold for tissue engineering is that it should resemble the properties of the tissues native extracellular matrix. A lot of advancements have been made in the last 10 years in the area of polymers used for tissue engineering applications and this chapter aims to provide a comprehensive coverage of the field.

This review focuses on the potential of polyvinylidene fluoride (PVDF) as tissue scaffolding materials. PVDF is defined in terms of the synthesis mechanisms and the method of the β phase formation process. General properties are fundamentally discussed in terms of their wettability and electroactive characteristics, which play an essential role in modifying other potential materials for tissue-based applications. The latest technologies for the replacement of artificial tissue scaffolds are evaluated, and the applications of PVDF-based scaffolds are discussed.

Pressure sensitive adhesives based on silicone materials are used particularly for skin adhesion, e.g., the fixation of electrocardiogram (ECG) electrodes or wound dressings. However, adhesion to sensitive tissue structures is not sufficiently addressed due to the risk of damage or rupture. We propose an approach in which a poly-(dimethylsiloxane) (PDMS)-based soft skin adhesive (SSA) acts as cellular scaffold for wound healing. Due to the intrinsically low surface free energy of silicone elastomers, functionalization strategies are needed to promote the attachment and spreading of eukaryotic cells. In the present work, the effect of physical adsorption of three different proteins on the adhesive properties of the soft skin adhesive was investigated. Fibronectin adsorption slightly affects adhesion but significantly improves the cellular interaction of L929 murine fibroblasts with the polymeric surface. Composite films were successfully attached to explanted tympanic membranes. This demonstrates the potential of protein functionalized SSA to act as an adhesive scaffold in delicate biomedical applications.

This paper aims to evaluate the mechanical behaviour of a bioresorbable polymeric coronary scaffold using finite element method, focusing on scaffold-artery interaction during degradation and vessel remodelling. A series of nonlinear stress-strain responses was constructed to match the experimental measurement of radial stiffness and strength for polymeric scaffolds over 2-year in-vitro degradation times. Degradation process was modelled by incorporating the change of material property as a function of time. Vessel remodelling was realised by changing the size of artery-plaque system manually, according to the clinical data in literature. Over degradation times, stress on the scaffold tended to increase firstly and then decreased gradually, corresponding to the changing yield stress of the scaffold material; whereas the stress on the plaque and arterial layers showed a continuous decrease. In addition, stress reduction was also observed for scaffold, plaque and artery in the simulations with the consideration of vessel remodelling. For the first time, the work offered insights into mechanical interaction between a bioresorbable scaffold and blood vessel during two-year in-vitro degradation, which has significance in assisting with further development of bioresorbable implants for treating cardiovascular diseases.

Bioglass® 45S5 (BG) has an outstanding ability to bond with bones and soft tissues, but its application as a load-bearing scaffold material is restricted due to its inherent brittleness. BG-based composites combine the amazing biological and bioactive characteristics of BG with structural and functional features of other materials. This article reviews the composites of Bioglass® in combination with metals, ceramics and polymers for a wide range of potential applications from bone scaffolds to nerve regeneration. Bioglass® also possesses angiogenic and antibacterial properties in addition to its very high bioactivity; hence, composite materials developed for these applications are also discussed. BG-based composites with polymer matrices have been developed for a wide variety of soft tissue engineering. This review focuses on the research that suggests the suitability of BG-based composites as a scaffold material for hard and soft tissues engineering. Composite production techniques have a direct influence on the bioactivity and mechanical behavior of scaffolds. A detailed discussion of the bioactivity, in vitro and in vivo biocompatibility and biodegradation is presented as a function of materials and its processing techniques. Finally, an outlook for future research is also proposed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3197-3223, 2017.

Carboxymethyl Chitosan (CMCh) is a semi-synthetic derivative of chitosan (a natural biopolymer) with increasing biomedical applications as a matrix or scaffold material for tissue engineering appli...

Three dimensional (3D) bioprinting technology enables the freeform fabrication of complex constructs from various hydrogels and is receiving increasing attention in tissue engineering. The objective of this study is to develop a novel self-supporting direct hydrogel printing approach to extrude complex 3D hydrogel composite structures in air without the help of a support bath. Laponite, a member of the smectite mineral family, is investigated to serve as an internal scaffold material for the direct printing of hydrogel composite structures in air. In the proposed printing approach, due to its yield-stress property, Laponite nanoclay can be easily extruded through a nozzle as a liquid and self-supported after extrusion as a solid. Its unique crystal structure with positive and negative charges enables it to be mixed with many chemically and physically cross-linked hydrogels, which makes it an ideal internal scaffold material for the fabrication of various hydrogel structures. By mixing Laponite nanoclay with various hydrogel precursors, the hydrogel composites retain their self-supporting capacity and can be printed into 3D structures directly in air and retain their shapes before cross-linking. Then, the whole structures are solidified in situ by applying suitable cross-linking stimuli. The addition of Laponite nanoclay can effectively improve the mechanical and biological properties of hydrogel composites. Specifically, the addition of Laponite nanoclay results in a significant increase in the Young's modulus of each hydrogel-Laponite composite: 1.9-fold increase for the poly(ethylene glycol) diacrylate (PEGDA)-Laponite composite, 7.4-fold increase for the alginate-Laponite composite, and 3.3-fold increase for the gelatin-Laponite composite.

Tissue engineering has the potential to regenerate tissue which regeneration capacity is limited. Nowadays, three-dimensional scaffold has become an excellent scaffold in tissue engineering. Chitosan as a scaffold material in tissue engineering is known for emerging techniques for treating some tissue damage, but there are questions that need to be answered, including application of chitosan and other materials, to provide growth factors, mechanical support and other micro environment, as well as the application at all levels, including conducive to an optimal and suitable cell source, the usability of growth factor, the selectivity of optimal biomaterial scaffolds as well as the technology for improving partial reconstruction of meniscus tears. This review focuses on current research on application of chitosan as scaffold material of construction In Vitro.

Decellularization involves removal of cellular material from tissue which results in a scaffold material consisting of only the extra cellular matrix (ECM). The effect of each individual decellularizing detergent on the final ECM scaffold and how that may differ from the combined use of these detergents is currently a gap in decellularization methodologies. This study evaluates the hypothesis that a synergistic effect exists when commonly used decellularization detergents are combined. This was evaluated with regard to decellularization efficiency, tissue strength, and collagen structure. Bovine pericardium was decellularized using a combination of 0.5% sodium dodecyl sulfate (SDS), 1% sodium deoxycholate (SDC) and 1% TritonX-100, and compared to the use of each detergent individually. The combined detergent decellularization protocol showed effective decellularization (p = .004), with minimal effects on tissue strength (p = .21) and structure (p = .21). Use of detergents individually, resulted in detrimental effects on tissue structure and integrity or ineffective decellularization. This study shows a synergistic relationship between SDS, SDC and TritonX-100 when combined at specific concentrations. The use of detergents in combination instead of individually appears to be superior, as it results in less ECM damage and improved decellularization effectivity.

Three-dimensional (3D) printing of core/shell filaments allows direct fabrication of channel structures with a stable shell that is cross-linked at the interface with a liquid core. The latter is removed post-printing, leaving behind a hollow tube. Integrating an additive manufacturing technique (like the one described here with tailor-made [bio]inks, which structurally and biochemically mimic the native extracellular matrix [ECM]) is an important step towards advanced tissue engineering. However, precise fabrication of well-defined structures requires tailored fabrication strategies optimized for the material in use. Therefore, it is sensible to begin with a set-up that is customizable, simple-to-use, and compatible with a broad spectrum of materials and applications. This work presents an easy-to-manufacture core/shell nozzle with luer-compatibility to explore core/shell printing of woodpile structures, tested with a well-defined, alginate-based scaffold material formulation.

Permanent therapeutically placed implants often used in situations when regeneration or transplantation are not practical or possible. They include metallic grafts for osteosynthesis, bulk metallic glasses, ceramics, and non-resorbable polymers providing mechanical support. Repair of the tissues on micro scale can also benefit from the biocompatible permanent implants. Vascular graft engineering and repairs of the spinal cord and peripheral nerves are among the most demanding application. Carbon fibers (CF) have superior mechanical and chemical properties, however, their long-time safety was never systematically estimated. The biggest concern comes from residual polymers used for pyrolysis and epoxy laminating resins. Here we attempted to investigate survival of the cells cultured on carbon fibers and to evaluate the tissue responses towards the long-term implanted material. Immortalized rat Schwann cells displayed efficient sporadic attachment to the carbon fibers with survival rate over 90%. Carbon fiber implants in adipose and on connective tissues were tolerable by animals during about 40% of their lifespan with no signs of inflammation on physiological, morphological or gene expression level.

Bioprinting is rapidly developing into a powerful tool in tissue engineering, for both organ printing and the development of in vitro models that can be used in drug discovery, toxicology and in vitro bioreactors. Nevertheless, the ability to create complex 3D culture systems with different types of cells and extracellular matrices integrated with perfusable channels has been a challenge. Here we develop an approach that combines the xurography of a scaffold material (cellulose) with extrusion printing of bioinks onto it, followed by assembly in a layer-by-layer fashion to create complex 3D culture systems that could be used as in vitro models of biological processes. This new method, termed ExCeL, can recapitulate the complexities of natural tissues with a proper 3D distribution of cells, extracellular matrices, and different molecules, while providing the whole structure with mechanical stability, and direct and easy access to the cells, even the ones that are positioned deep in the bulk of the structure, without the need to fix or section the samples. Briefly, the bioprinting of predefined patterns with a feature size of ∼1 mm has been made possible by treating paper with the hydrogel's crosslinker and printing cell-embedded hydrogel that will solidify immediately upon contact with the paper. These impregnated layers can be used as single layers or in a layer-by-layer approach by stacking them (here up to four layers) for applications such as cell migration and proliferation in 3D structures composed of collagen or alginate. Cells are generally sensitive to the amount of FBS in their culture media and we have shown how FBS amount will effect cell migration. By cutting the paper in certain patterns, printing hydrogel on the remaining parts of it, and stacking the paper in layers, features like embedded channels are formed that will provide cells will better mass transfer in thick structures. This technique provides biologists with a unique tool to perform sophisticated in vitro assays.

For tissue scaffolding, it is desirable for the scaffold to promote growth of the native tissue, before the scaffold is ultimately replaced by tissue. While polycaprolactone (PCL) is a superb scaffold material, it is impossible to non-invasively monitor its degradation. Here, incorporating fluorescent nanodiamonds into PCL, we show sub-dermal fluorescence imaging of PCL. This provides an opportunity to monitor PCL degradation to assess real-time tissue uptake and replacement. Furthermore, nanodiamonds increase the hydrophillicity PCL, and hence may increase tissue uptake rates, opening new applications for PCL.

Thermo-sensitive methylcellulose (MC) hydrogel has been widely used as a scaffold material for biomedical applications. However, due to its poor mechanical properties, the MC-based hydrogel has rarely been employed in 3D bioprinting for tissue engineering scaffolds. In this study, the dual crosslinkable tyramine-modified MC (MC-Tyr) conjugate was prepared via a two-step synthesis, and its hydrogel showed excellent mechanical properties and printability for 3D bioprinting applications. The MC-Tyr conjugate formed a dual-crosslinked hydrogel by modulating the temperature and/or visible light. A combination of reversible physical crosslinking (thermal crosslinking) and irreversible chemical crosslinking (photocrosslinking) was used in this dual crosslinked hydrogel. Also, the photocrosslinking of MC-Tyr solution was facilitated by visible light exposure in the presence of biocompatible photoinitiators (riboflavin, RF and riboflavin 5'-monophophate, RFp). The RF and RFp were used to compare the cytotoxicity and salting-out effect of MC-Tyr hydrogel, as well as the initiation ability, based on the difference in chemical structure. Also, the influence of the printing parameters on the printed MC hydrogel was investigated. Finally, the cell-laden MC-Tyr bioink was successfully extruded into stable 3D hydrogel constructs with high resolution via a dual crosslinking strategy. Furthermore, the MC-Tyr scaffolds showed excellent cell viability and proliferation.

The repair and regeneration of large bone defects resulting from disease or trauma remains a significant clinical challenge. There has been increasing interest in using bioactive glass as a scaffold material for bone tissue engineering due to its appealing characteristics. However, the application of glass scaffolds for the repair of load-bearing bone defects is often limited by their low mechanical strength and fracture toughness. This chapter focuses on recent advances in the development and use of bioactive glass scaffolds for bone tissue engineering applications. Scaffolds with compressive strengths comparable to those of trabecular and cortical bones have been achieved using a variety of processing methods. The low fracture toughness (low resistance to fracture) and limited mechanical reliability remain key limitations for bioactive glass scaffolds. Multiple approaches to manipulate the structure and performance of bioactive glass are discussed. Future research directions including the development of strong and tough bioactive glass scaffolds and their evaluation in unloaded and load-bearing bone defects in animal models are recommended.

Ionic liquids (ILs) present many new opportunities for the field of sol–gel chemistry. When conducted in an IL medium, sol–gel chemistry can produce novel silica structures as well as hybrid materials known as ionogels, which feature ILs supported by a solid scaffold material. In this work, the influence of reactive formulation on the properties of silica-supported ionogels is reported. A simple, non-hydrolytic sol–gel reaction between tetramethoxysilane and formic acid is employed to create silica-supported ionogels that exhibit wide variations in silica content, gelation time, and mechanical character. The influence of formulation on gelation time is demonstrated, and it is shown that a range of formulations can be used to produce soft, mechanically compliant ionogels. Furthermore, either brittle or compliant ionogels can be realized via rapid- or slow-gelling formulations. It is observed that the speed of gelation influences the pore structure in the resultant silica scaffold, thereby enabling different mechanical characters to be achieved for ionogels containing equivalent silica mass fractions.

Biomimetic extracellular matrix (ECM) topographies driven by the magnetic‐field‐directed self‐assembly of ECM protein‐coated magnetic beads are fabricated. This novel bottom‐up method allows us to program isotropic, anisotropic, and diverse hybrid ECM patterns without changing other physicochemical properties of the scaffold material. It is demonstrated that this 3D anisotropic matrix is able to guide the dendritic protrusion of cells.

Scaffolds material is the key factor for bone tissue engineering, and construction of the scaffolds is also an important part. Adopting the biocompatible, biodegradable, hydroxyapatite and sodium alginate as the moulding material, using 3D printing technology, choosing different filling paths. The research based on the artificial bones which manufactured by self-developed 3D printing equipment. Then, the work measured and analysed important parameters, optimised the best filling path and re-used this path to prepare the bone scaffold for bone defect repair experiment. At different time points, we observed the situation of bone defects repair to verify whether the scaffold material has the properties of bone substitution. The paper provides a reference for the study of bone tissue engineering materials.

For an ideal scaffolding material, properties are required that include biocompatibility, suitable microstructure, desired mechanical strength and degradation rate as well as most importantly the ability to support cell residence and allow retention of metabolic functions. Numerous strategies currently used to engineer tissues depend on employing a material scaffold. These scaffolds serve as a synthetic extracellular matrix (ECM) to organize cells into a 3D architecture and to present stimuli, which direct the growth and formation of a desired tissue. Depending on the tissue of interest and the specific application, the required scaffold material and its properties will be quite different.

The aims of this study is to determine the mechanical characteristics of the calcinated scaffold material bovine hydroxyapatite (BHA) for bone filler applications. Scaffold BHA was obtained from femur section of bovine bones which cut into 10x10x10 mm. Scaffold BHA was calcinated by temperature variations of 900ºC and 1200°C for 2 hours with 10ºC/min as the amount of the increasing level. The study result of each scaffold BHA which had been calcinated by 900°C and 1200°C has a hardness value of 8.48 ± 0.1118 VHN and 12.37 ± 0.5803, meanwhile the compressive strength value of each scaffold BHA samples is 3.03 ± 0.6764 MPa and 1.96 ± 0.3450 MPa. The porous on scaffold BHA samples calcinated by 900°C and 1200°C which had been observed by SEM had porous size that is not much different, it was ± 200-400 μm, the difference can be seen from the smaller porous size of the scaffold BHA calcination 1200°C compared to the porous size of scaffold BHA calcination 900°C.

The development of tissue engineering provides a new way for the repair and reconstruction of meniscal injury. Using this technology to build a functional meniscus in the prevention of complications after meniscectomy has important significance. Because of the blood supply characteristics of the meniscus, meniscal injury caused no blood flow region do not have the ability to heal. The development of tissue engineering provides a new way for the repair and reconstruction of meniscal injury. The repair of meniscal scaffold materials more reports mainly include natural biological materials, synthetic materials, nanomaterials etc. The study of tissue engineering meniscus has achieved initial results, but are in the experimental stage of the scaffold material, there is no an ideal material. Therefore, the search for a good cell compatibility, controllable degradation rate and hot research has certain mechanical strength of scaffold materials is still the meniscus tissue engineering.

Tissue regeneration relies on building carefully crafted scaffold material in the micron–submicron scale and imparting specific functionality in order to best mimic the in vivo environment in terms of chemical composition, morphology, and surface functional groups. Fibrous meshes with structural features at the micron to submicron level for ideal three-dimensional tissue regeneration scaffolds can be an inexpensive scale-up option. Bio-inert polymers lack the functional motifs for specific bioactivity; however, functionalization of the scaffolds can provide biological functions to actively induce tissue regeneration and promote cell adhesion by targeting specific cell–matrix interactions. It is therefore important to characterize the scaffolds and understand the relationship between the efficacy of the functionalization, the surface properties of the scaffolds, and their biological performance. This paper is a comprehensive review of the current understanding in functionalization and characterization of fibrous scaffolds and their biological efficacy. We begin with a compilation of various functionalization schemes including physical adsorption, co-electrospinning, wet chemical techniques, and surface graft polymerization methods and their application to fibers. After a critical literature review, the state of the art for characterization of these functionalized nano-fibers is then discussed. We emphasize the importance of covalent binding of biomolecules and the subsequent need for characterization of functional group distribution, or local density of functionalization, on the scaffold surface. Current challenges and future directions are outlined so that quantitative characterization of scaffold surfaces can aid in the development of next generation scaffolds.

Cartilage tissue engineering uses a combination of biocompatible scaffold material, cells, and growth factors to achieve a cartilage-like tissue that has similar biomechanical properties as a native cartilage. After initial success at-bench, most tissue growth strategies are tested in animals. In vivo animal models of cartilage tissue engineering provide a proof-of-concept validation for promising at-bench tissue-growth strategies. A number of animal models such as mice, rats, rabbits, sheep, dogs, and horses have been used for the purpose of validating emerging cartilage tissue-engineering approaches. Out of all the available choices for monitoring cartilage tissue engineering and regeneration in vivo, magnetic resonance imaging (MRI) is the most suitable and is the leading imaging modality for noninvasive longitudinal quantitative monitoring of cartilage tissue growth and regeneration. This chapter describes advances made in MRI assessment and monitoring of cartilage tissue engineering in vivo during the last decade.

In tissue-engineered (TE) heart valves, cell-mediated processes cause tissue compaction during culture and leaflet retraction at time of implantation. We have quantified and correlated stress generation, compaction, retraction, and tissue quality during a prolonged culture period of 8 weeks. Polyglycolic acid /poly-4-hydroxybutyrate strips were seeded with vascular-derived cells and cultured for 4-8 weeks. Compaction in width, generated force, and stress was measured during culture. Retraction in length, generated force, and stress was measured after release of constraints at weeks 4, 6, and 8. Further, the amount of DNA, glycosaminoglycans (GAGs), collagen, and collagen cross-links was assessed. During culture, compaction and force generation increased to, respectively, 63.9% +/- 0.8% and 43.7 +/- 4.3mN at week 4, after which they remained stable. Stress generation reached 27.7 +/- 3.2 kPa at week 4, after which it decreased to similar to 8.5 kPa. At release of constraints, tissue retraction was 44.0% +/- 3.7% at week 4 and decreased to 29.2% +/- 2.8% and 26.1% +/- 2.2% at, respectively, 6 and 8 weeks. Generated force (8-16mN) was lower at week 6 than at weeks 4 and 8. Generated stress decreased from 11.8 +/- 0.9 kPa at week 4 to 1.4 +/- 0.3 and 2.4 +/- 0.4 kPa at, respectively, weeks 6 and 8. The amount of GAGs increased at weeks 6 and 8 compared to week 4 and correlated to the reduced stress and retraction. In summary, prolonged culture resulted in decreased stress generation and retraction, likely as a result of the increased amount of GAGs. These results demonstrate the potential of prolonged tissue culture in developing functional, nonretracting, TE heart valves.

Tissue engineering aims to produce biological substitutes to restore or repair damaged human tissues or organs. The principle strategy behind tissue engineering involves seeding relevant cell(s) onto porous 3D biodegradable scaffolds. The scaffold acts as a temporary substrate where the cells can attach and then proliferate and differentiate. Collagen is the major protein constituent of the extracellular matrix in the human body and therefore an attractive scaffold material. Current collagen scaffolds are foams which limit the mass transport of oxygen and nutrients deep into the scaffold, and consequently cannot support the growth of thick-cross sections of tissue (greater than 500 μm). We have developed a novel process to make collagen and collagen-hydroxyapatite scaffolds containing an internal artificial circulatory system in the form of branching channels using a sacrificial mould, casting and critical point drying technique. The mould is made using a commercial rapid prototyping system, the Model-Maker II, and is designed to possess a series of connected shafts. The mould is dissolved away and the solvent itself removed by critical point drying with liquid carbon dioxide. Processed hydroxyapatite has been characterised by XRD and FTIR analysis. Tissue engineering with collagen scaffolds possessing controlled internal microarchitecture may be the key to growing thick cross-sections of human tissue.

The scaffold is a key part of the artificial regeneration osseous tissues. The ideal scaffold will have the ability to mimic the fully functional tissue, which can afford the fibrous form and complex function of the native ECM. Although Low-temperature deposition manufacturing is a promising method for fabricate tissue scaffold because scaffold can maintain a good performance of biomaterials in low temperature, the scaffold pore size can not be controlled according to demands. Therefore, the key factors that affect the pore size of bone scaffolds are firstly analyzed. Then the mechanism for on-line control is given. Finally, an automatic control system is proposed and some experimental results are given, which have demonstrated the effects of processing parameters on the Shaping of scaffold material.

Cellulose perforated by micro-channels (phi? similar to 500 mu m) has been investigated as a potential future scaffold material for meniscus implants. Scaffolds seeded with 3T6 fibroblasts were cultivated with mechanical stimulation in a compression bioreactor for enhanced collagen production. Constructs under dynamic compression at a frequency of 0.1 Hz and compression strain of 5% were compared to static cultures used as controls. The three-dimensional distributions of collagen fibers and fibroblasts in the cellulose scaffolds were studied under native, soft-matter conditions by combined second harmonic generation and coherent antiStokes Raman scattering microscopy, requiring no artificial sample preparation. Results showed that the micro-channels facilitated the alignment of cells and collagen fibers and that collagen production was enhanced by mechanical stimulation. Thus, cell-seeded, micro-channeled cellulose scaffolds provided guided tissue growth required to obtain an ultrastructure mimicking that of the meniscus.

The repair and regeneration of large bone defects resulting from disease or trauma remains a significant clinical challenge. Bioactive glass has appealing characteristics as a scaffold material for bone tissue engineering, but the application of glass scaffolds for the repair of load-bearing bone defects is often limited by their low mechanical strength and fracture toughness. This paper provides an overview of recent developments in the fabrication and mechanical properties of bioactive glass scaffolds. The review reveals the fact that mechanical strength is not a real limiting factor in the use of bioactive glass scaffolds for bone repair, an observation not often recognized by most researchers and clinicians. Scaffolds with compressive strengths comparable to those of trabecular and cortical bones have been produced by a variety of methods. The current limitations of bioactive glass scaffolds include their low fracture toughness (low resistance to fracture) and limited mechanical reliability, which have so far received little attention. Future research directions should include the development of strong and tough bioactive glass scaffolds, and their evaluation in unloaded and load-bearing bone defects in animal models.

One of the major challenges for bone tissue engineering is the production of a suitable scaffold material. In this review the currently available composite material options are considered and the methods of production and assessing the scaffolds are also discussed. The production routes range from the use of porogens to produce the porosity through to controlled deposition methods. The testing regimes include mechanical testing of the produced materials through to in vivo testing of the scaffolds. While the ideal scaffold material has not yet been produced, progress is being made.

Scaffold-based tissue engineering strategies often face the problem of tissues forming only within the periphery layers of the scaffold due to mass transfer issues. In the present study, we attempt to overcome this limitation by incorporating a three-dimensional (3D) interconnected network of channels within the scaffold as part of the fabrication process so as to enhance nutrient delivery and cell migration. A scaffold material with the ability to foam was also used in conjunction with this process in order to produce highly interconnected pores within the scaffold. This article describes the developmental process of an indirect fabrication approach which involves the application of rapid prototyping (RP) technology as well as the use of a foaming scaffold material to produce highly and uniformly porous scaffolds with complex channel architectures. Finally, cytotoxicity assessment confirmed that the multiple steps involved in the fabrication process did not induce toxicity within the scaffold.

Tissue engineering, often referred to as regenerative medicine and reparative medicine, is an interdisciplinary field that necessitates the combined effort of cell biologists, engineers, material scientists, mathematicians, geneticists, and clinicians toward the development of biological substitutes that restore, maintain, or improve tissue function. It has emerged as a rapidly expanding approach to address the organ shortage problem and comprises tissue regeneration and organ substitution. Cells placed on/or within constructs is the most common strategy in tissue engineering. Successful cell seeding depends on fast attachment of cell to scaffolds, high cell survival and uniform cell distribution. The seeding time is strongly dependent on the scaffold material and architecture. Scaffolds provide an initial biochemical substrate for the novel tissue until cells can produce their own extra-cellular matrix (ECM). Thus scaffolds not only define the 3D space for the formation of new tissues, but also serve to ...

A shape memory fiber was prepared and a corresponding shape memory fabric was fabricated by knitting using the prepared shape memory fiber. Both the fiber and fabric showed good shape memory properties. The prepared fiber had much higher mechanical strength than that of corresponding shape memory films due to molecular orientation caused by the spinning process. The biological evaluations of the prepared shape memory fabric were preliminarily assessed in terms of cytotoxicity, hemolysis, sensitization and dermal irritant. The test results show that the shape memory fabric is not cytotoxic, hemolytic, sensitive, or irritant. Due to the special format of shape memory fiber/fabric being more compatible with human bodies compared with shape memory films or bulks, the shape memory fiber/fabric may find broad application in biomedical areas such as artificial tendon, artificial cornea, hernia repair, artificial bone joints, orthodontics, scaffold material, and wound dressing.

We describe the structure of biodegradable chitosan-nanohydroxyapatite (nHA) composites scaffolds and their interaction with pre-osteoblasts for bone tissue engineering. The scaffolds were fabricated via freezing and lyophilization. The nanocomposite scaffolds were characterized by a highly porous structure and pore size of ∼50–125 μm, irrespective of nHA content. The observed significant enhancement in the biological response of pre-osteoblast on nanocomposite scaffolds expressed in terms of cell attachment, proliferation, and widespread morphology in relation to pure chitosan points toward their potential use as scaffold material for bone regeneration.

The aim of the present study was to test the hypothesis that both scaffold material and the type of cell culturing contribute to the results of in vivo osteogenesis in tissue-engineered constructs in an interactive manner. CaCO3 scaffolds and mineralized collagen scaffolds were seeded with human trabecular bone cells at a density of 5 × 106 cells/cm3 and were left to attach under standard conditions for 24 h. Subsequently, they were submitted to static and dynamic culturing for 14 days (groups III and IV, respectively). Dynamic culturing was carried out in a continuous flow perfusion bioreactor. Empty scaffolds and scaffolds that were seeded with cells and kept under standard conditions for 24 h served as controls (groups I and II, respectively). Five scaffolds of each biomaterial and from each group were implanted into the gluteal muscles of rnu rats for 6 weeks. Osteogenesis was assessed quantitatively by histomorphometry and expression of osteocalcin (OC) and vascular endothelial growth factor (VEGF) was determined by immunohistochemistry. CaCO3 scaffolds exhibited 15.8% (SD 3.1) of newly formed bone after static culture and 22.4% (SD 8.2) after dynamic culture. Empty control scaffolds did not show bone formation, and scaffolds after 24 h of standard conditions produced 8.2% of newly formed bone (SD 4.0). Differences between the controls and the scaffolds cultured for 14 days were significant, but there was no significant difference between static and dynamic culturing. Mineralized collagen scaffolds did not show bone formation in any group. There was a significant difference in the expression of OC within the scaffolds submitted to static versus dynamic culturing in the CaCO3 scaffolds. VEGF expression did not show significant differences between static and dynamic culturing in the two biomaterials tested. It is concluded that within the limitations of the study the type of biomaterial had the dominant effect on in vivo bone formation in small tissue-engineered scaffolds. The culture period additionally affected the amount of bone formed, whereas the type of culturing may have had a positive effect on the expression of osteogenic markers but not on the quantity of bone formation. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009

Porous scaffolds are considered a key strategy in the concept of bone tissue engineering. Hydroxyapatite, which is a bioceramic has been used as a popular scaffold material due to its bioactive and osteoconductive properties. A combination of slurry-dipping and electrospraying has been used as a new foam fabrication method to produce porous and interconnected foam structures. The combined method has shown to overcome the shortcomings of the individual methods and it has produced open pores in the desired range of 100-350 microm. The porosity which was determined by calculation and microtomography was between 84% and 88%. Reduced cracks and thicker struts were observed in the microstructure, pointing to improved mechanical properties.

Decellularized extracellular matrix has long been applied as a scaffold material in tissue engineering. Recent investigation into decellularized whole solid organs has shown that the remaining extracellular matrix preserves the underlying architecture and protein organization inherent to the tissue. Decellularized whole organ scaffolds are of particular interest to renal regeneration owing to the complex nature of the kidneys because the extracellular matrix contains intact vascular and tubular networks. This chapter summarizes recent developments in whole organ scaffolds for kidney regeneration.

Aplysia californica is presented as a novel source of actuator and scaffold material for biohybrid robots. Collagen isolated from the Aplysia skin has been fabricated into gels and electrocompacted scaffolds. Additionally, the I2 muscle from the Aplysia buccal mass had been isolated for use as an organic actuator. This muscle has been characterized and the maximum force was found to be 58.5 mN with a maximum muscle strain of 12 ± 3 %. Finally, a flexible 3D printed biohybrid robot has been fabricated which is powered by the I2 muscle and is capable of locomotion at 0.43 cm/min under field stimulation.

A mixture of agarose, MEM IX and HeLa cells (dubbed Bio-Ink) was created to allow normal cell interaction with the scaffold material (agarose) before crosslinking as an initial step in 3D printing tissue. Bio-Ink was developed successfully as an in situ-scaffolding material for engineering biological structures. Bio-Ink has been further conditioned by adjusting agarose composition and gelling time to obtain optimal HeLa cell growth. After detailed study, the time range available for printing this material, before full crosslinking occurs, was determined to be about 300 s, giving it attractive properties for 3D printing. Repeatable 10 mm thick prints were successful, although more system calibration is still needed to achieve more complex prints.

In spite of many researches on scaffold material design, fabrication and characterization, as well as cell-material interaction in vitro, in vivo study especially in large mammals should be an essential step towards practical application. In our center, different scaffold materials have been applied to the reconstruction of various types of tissues using immunocompetent mammals as major animal models, such as for reconstruction of bone, cartilage, tendon, skin, blood vessel and corneal stroma, etc. In this article, our experience, as well as encountered challenges in the application of scaffold materials, is introduced. Additionally, future requirements for scaffold application in tissue reconstruction and regeneration are proposed as well.

Lecithin was, for the first time, blended with PLLA to prepare scaffold material for tissue engineering applications in the present study. Solution blending was used to incorporate Lecithin (containing 0–10 wt %) with PLLA to enhance the blend films biocompatibility, hydrophilicity and toughness while maintaining mechanical strength of PLLA. The results of FTIR-ATR analysis indicated that the amino groups of lecitin existed in the films. DSC analysis indicated that Tg decreased with the increase of lecithin content in the blend films. The percentage elongation markedly increased with increase of lecithin content. The proliferation and viability of the vascular smooth muscle cell cultures on PLLA/Lecithin (containing 3–7 wt %) films were significantly enhanced compared to pure PLLA on tissue culture plates. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

Porous hydroxyapatite (HAP) foam permits three-dimensional (3D) structure with fully interconnecting pores as well as excellent tissue response and good osteoconductivity. It is therefore thought to be a good candidate as scaffold material for bone regeneration and as a synthetic bone substitute material. To fabricate better porous HAP foam, improved physical and structural properties as well as higher osteoconductivity are desired. In the present study, the effects of sintering temperature on the physical and compositional properties of porous HAP foam were evaluated by employing high sintering temperature starting at 1,300 degrees C up to 1,550 degrees C. The mechanical strength of porous HAP foam increased with sintering temperature to reach the maximum value at 1,525 degrees C, then decreased slightly when sintering temperature was further increased to 1,550 degrees C. Alpha tricalcium phosphate (alpha-TCP) was formed, and thus the porous HAP foam became biphasic calcium phosphate. Biphasic calcium phosphate consisting of both alpha-TCP and HAP had been reported to show higher osteoconductivity than HAP alone. We therefore recommend 1,500-1,550 degrees C as the sintering temperature for porous HAP foam since this condition provided the most desirable physical properties with biphasic calcium phosphate composition.

The field of tissue engineering has created a need for biomaterials that are capable of providing biofunctional and structural support for living cells outside of the body. Most of the commonly used biomaterials in tissue engineering are designed based on their physicochemical properties, thus achieving precise control over mechanical strength, compliance, porosity, and degradation kinetics. Biofunctional signals are added to the scaffold by tethering, immobilizing, or supplementing biofunctional macromolecules, such as growth factors, directly to the scaffold material. The challenge in tissue engineering remains to find the correct balance between the biofunctional and the physical properties of the scaffold material for each application. Moreover, the ability to modulate communication between cells and the extracellular environment using the engineered scaffold as the actuator can provide a significant advantage in tissue engineering. In this study, a unique scaffold material is presented. The material interchangeably combines biofunctional and structural molecules by fusing the two into a single backbone macromolecule. This integration provides the basis for practical, effective, and high-resolution control of both the biofunctional and the physical properties of the scaffold material. This new scaffold material has proven effective with smooth muscle, cardiac, cartilage, and human embryonic stem cell cultures. The advantages of this approach as well as the potential applications of this unique scaffold material are discussed.

Up to now, effectively assembling micro biomimetic CaCO 3 particles to form a functional material is still an important research topic. In our study, bacterial cellulose is used to in-situ assemble micro biomimetic lamellar CaCO 3 particles induced by egg white and a new hybrid is obtained. Experimental data suggests that the hybrid has a rough surface and an elaborate three-dimensional structure with controllable porosity and the cycle stress–strain curves show that it has fairly good elasticity. Its hardness is adjustable allowing it to become comparable to the middle hardness plastic during a 72 h mineralization procedure. The analysis on its application prospects shows that it is very suitable to be used as a multifunctional scaffold material in different fields of tissue engineering.