In some cases, as with Chronicles of Narnia , disagreements about order necessitate the creation of more than one series. If the series has an order, add a number or other descriptor in parenthesis after the series title eg. By default, it sorts by the number, or alphabetically if there is no number. If you want to force a particular order, use the character to divide the number and the descriptor. So, " 0 prequel " sorts by 0 under the label "prequel. Series was designed to cover groups of books generally understood as such see Wikipedia: Like many concepts in the book world, "series" is a somewhat fluid and contested notion.
A good rule of thumb is that series have a conventional name and are intentional creations , on the part of the author or publisher.
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For now, avoid forcing the issue with mere "lists" of works possessing an arbitrary shared characteristic, such as relating to a particular place. Avoid series that cross authors, unless the authors were or became aware of the series identification eg. Also avoid publisher series, unless the publisher has a true monopoly over the "works" in question. So, the Dummies guides are a series of works. But the Loeb Classical Library is a series of editions, not of works.
Home Groups Talk Zeitgeist. The 12 Days of LT scavenger hunt is going on. Can you solve the clues? I Agree This site uses cookies to deliver our services, improve performance, for analytics, and if not signed in for advertising. Your use of the site and services is subject to these policies and terms. Common Knowledge Series X-Zone. For example, cell differentiation and ECM production could be influenced by surface area, pore size and interconnectivity of the scaffold mesh. Switching gene expression from type I collagen to type II collagen, cell density and distribution uniformity throughout the scaffold as well as comparable mechanical properties to native articular cartilage indicated that this scaffold is applicable for articular cartilage repair [ ].
ECM molecules of cartilage could regulate metabolism and gene expression in chondrocytes as well as stimulate cell proliferation and differentiation [ ]. It was reported that chondroitin sulphate presence could influence mechanical properties of the scaffold, demonstrating its incorporation with desired guest materials could enhance compressive strength due to proteoglycan secretion promotion [ ].
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They studied the effect of hydrogel composition and crosslinking agent content on the physico-chemical, and mechanical properties of the scaffold. As a result, the surface of the hydrogel not only could fill the cartilage defect without any inflammation but also could integrate with surrounded tissues. Therefore, chondroitin sulphate release from the scaffold due to biodegradability could play an important role in articular cartilage repair for regulate metabolism.
In a different approach, Ko and coworkers [ ] attempted to mimic the native ECM of articular cartilage by incorporating type II collagen with chondroitin sulphate and hyaluronan to up-regulate biosynthetic activities. This group used freeze-drying and chemical crosslinking procedures to fabricate highly porous and interconnected network composite scaffold.
Since type II collagen provides mechanical properties such as tensile strength which influences the bioactivity of the seeded chondrocytes and performs important biological functions, its incorporation of type II collagen with chondroitin sulphate could show synergistic effect on cartilage repair [ ]. Not only material properties and scaffold pore structure could influence cell fate but also applying mechanical forces such as pressure gradient, fluid flow, mechanical strain can support and regulate chondrogenic lineage of MSCs [ ].
They used Response Surface Method to predict the incorporation of GAGs with chitosan then the optimal formulation with considering proper amounts and ratios was predicted [ ]. In line with this, incorporation of gelatin, chondroitin sulphate with hyaluronan in fibrin glue, which makes a suitable environment for cell distribution and seeding was assessed by Chou et al. Due to its beneficial intrinsic properties such as biodegradablity, biocompatiblity, nonantigenicity, nontoxicity, biofunctionality, antimicrobiality besides similar characteristics with various GAGs and hyaluronic acid present in articular cartilage, it is well known functional aid in terms of connective tissue in-growth and neo-vascularization for the ordered regeneration of human cartilage tissues [ 9 , ].
Although chitosan has a lot of intrinsic properties, which make it applicable for tissue engineering applications, but chitosan suffers from a relatively poor mechanical characteristic, therefore preparing blends and composites with other biomaterials attracted much interest [ , ]. Incorporation of chitosan into another biopolymer, such as collagen and alginateimproved its mechanical property and reduced the biodegradation rate [ ].
In order to improve cell attachment, cell proliferation and biosynthetic production as well as spherical morphology maintenance, blending and surface modification with chitosan are two important approaches [ ]. Alginate, a family of polyanionic copolymers derived from brown sea algae, could promote cell proliferation, maintain cell functionality and enhance phenotype [ ]. Combining chitosan with alginate led to increased cell viability, promoted production of type II collagen as well as retaining spherical morphology; therefore, these scaffolds could be used for cartilage repair.
A new approach to prevent osteoarthritis development was attempted by Oprenyeszk et al. The porosity was kept constant while improving cell functionality and induction differentiation. This was probably due to overcoming on confined high aggregation of cells within a small region. Furthermore mechanical properties such as elasticity improved relatively to PCLC alone and deformation recovery ratio was very similar to native tissue.
The confined high aggregation of cells within a small region in the PCLC scaffold might have caused a deficit in nutrient supply locally, thus impeding long-term cellular proliferation [ ]. Fabrication of PVA hydrogels via freeze-thaw process makes them to exhibits mechanical properties approximately similar to articular cartilage [ ]. Moreover, it seems that the PVA plays an effective role for chondrocyte activity [ ].
In view of this, its clinical applications are still limited due to limited stability for long-term utility, and non-bioactivity in vivo in comparison with native cartilage [ 31 ]. There are some techniques to modify PVA, for instance, co-polymerization, blending, or compositing with nanoscale materials [ 31 , ]. Such modification may influence biological properties such as biocompatibility or cytocompatibility of composites hence selecting suitable second material could be challenging [ ]. However PVA was a candidate material for articular cartilage repair, preparation PVA with acrylamide as a crosslinking agent was one of strategies used to increase PVA water permeability thereby improving the lubrication for articulation [ 31 , ].
Adding hydrophilic polymers such as polyethylene glycol or acrylamide while preparation could be an approach to increase lubricity as well as stability by preventing pore collapses due to removing from the hydrogels. The presence of hydrogen bonding between hydroxyl groups of polymer surface and polar groups on cell surface makes PVA to be very adhesive for cells but this property should be tailored.
PCL with hydrophobicity has been well known for cell attachment therefore this property would be controlled by blending these polymers together to balance hydrophilic-hydrophobic moieties. They reported that PCL acted as reinforcement for PVA in the semi IPN scaffold with viscoelastic characteristics, provided a favorable cell environment for GAG secretion as well as good medium uptake ability; hence the supply of nutrients to cells penetrated within the scaffold would be adequate [ ]. It was shown that the scaffold microenvironment promoted better differentiation of MSCs to chondrocytes.
Preparation of blends based on biomaterials with similar structure to ECM or with similar mechanical properties to hyaline cartilage could be appropriate strategy for articular cartilage repair. NOCC induces suitable results in regard to articular cartilage, because it is a derivative of chitosan, a semi-natural polymer similar to GAGs and may play role in modulating the morphology, differentiation, and function of chondrocytes.
In line with this, Ibrahim et al. Tribiology and wear characteristic of PVA as an articular cartilage replacement as well as wear mechanism in reciprocating sliding against articular cartilage under certain conditions was assessed by Sardinha et al. These authors demonstrated that very low friction coefficient values from 0. To increase water absorption of PVA hydrogel, Polyvinylpyrrolidone PVP , is a good alternative material for blending due to amide groups with strong hydrophilicity rather than hydroxyl and carboxyl groups.
Enhanced water content value up to 1. The presence of bovine serum as a lubrication fluid in the blended material showed minimal wear behavior friction coefficient: Long fixation of scaffolds comprised of PVA could be achieved by preparation of hydrogel scaffolds contain inter-connected porous network. The authors demonstrated that the presence of internal porous network within hydrogel not only could facilitate integration with the host tissue as well as promoting inward cellular migration but also the blended scaffold could perfectly control load bearing behavior similar to that of articular cartilage after implantation [ ].
In another study, Bichara et al. Articular cartilage tissue shows unique combinations of nonlinear properties as well as anisotropic behaviors due to composition and orientation of tissue components [ 63 ]. Scientists have been interested in regenerating articular cartilage using nanobiomaterials to achieve similar mechanical and physical properties with the natural tissue [ ]. Nanocomposite refers to multiphase materials at the nanometric scale within polymer matrix could mimic native tissue properties; therefore, it could be another approach to gain this goal.
These nanobiomaterials in different shapes, such as particles, fibers, etc. It has been reported that ECM mimicry and maintenance of the chondrocytic phenotype are enhanced or promoted on the nanofiber scaffolds [ ]. Furthermore, Casper et al. They have reported that coating does not support cell penetration, proliferation and chondrogenic differentiation while this notion is in contrast to several published reports [ ].
Likewise, Wise et al. In another research, Coburn et al. The low density scaffolds were cultured with MSCs for six weeks in both chondrogenic induction medium and in vivo. The presence of PVA with non-adhesive nature not only resulted in fibroblast invasion reduction in vivo but also enhanced GAG production while the presence of chondroitin sulfate in the fibers had a positive impact on increasing type II collagen synthesis and mechanical properties of tissues.
Cell proliferation and differentiated into the chondrogenic lineage were confirmed by producing patterned ECM features and cartilage specific gene expression due to early cell infiltration and cartilage repair in an in vivo osteochondral defect of rat model [ ]. Cellular responses such as GAG content, DNA content, as well as physical and mechanical properties, showed these blends were appropriate candidates for articular cartilage regeneration [ ].
Polymer-silica composites are another attractive class of materials for cartilage regeneration [ ]. For example, Buchtova et al. The nanocomposite possessed dispersion at the nanoscale due to the chemical affinity between the hydrophilic silica nanofibers and the pendant silanolate groups of the polymer chains influenced gel point. Tuning the amount of nanocharges resulted by adding small amount of anisotropic, rod-like shape of the silica nanofibers, mechanical properties of the nanocomposite supported cartilage tissue requirements.
Despite this, low compressive elastic moduli in comparison with native tissue caused them not to be applicable for articular cartilage repair except as a favorable environment for cells [ ]. This nanocomposite could improve adhesion of the hydrogel on underlying bone with high bond strength so that it could not be loosen their integrities under applied loads [ 80 ]. Although these results show the improvement of durability of hydrogel and adhesion to the underlying tissue, further study is required in order to mimic composition and zonal organization of articular cartilage. Enhancement of hydrogel mechanical properties, control and sustained co -delivery of biomacromolecules and therapeutic agents, as well as induce chondrogenicity function, are achieved by using mesoporous structure of silica nanoparticles.
Introduction of nanoparticles with the rigid structure in hydrogels and then the existence of strong intermolecular interaction between nanoparticles silanol groups as well as chitosan susceptible groups resulted in improving hydrogel strength. Chitosan could use as a drug delivery system for biomacromolecules due to its positive charges but studies demonstrated a difficulty for hydrophilic drugs [ ].
Introducing silica nanoparticle with mesoporous structure could resolve the release problem as well as produced GAGs and DNA demonstrate chondrocyte fate promotion due to lower concentration of released silicate ions in the inner environment [ 28 ]. Hydroxyapatite nanocomposites have been used in several application fields especially in bone tissue engineering [ ].
Hydroxyapatite is a biocompatible and bioactive material for construction of bone composition and it is osteoconductive [ ]. Many studies demonstrated polymer-hydroxyapatite nanocomposites can stimuli osteoblast growth and proliferate [ ]; however, there are also some studies regarding to cartilage tissue engineering and cartilage replacement [ , ]. The incorporation of these nanopoarticles with polymers, such as PVA, PLLA and chitosan can obviate some drawbacks of pure hydrogels by enhancing its physical and mechanical properties, biocompatibility, bioactivity and elasticity [ , , ].
The use of bilayered or biphasic scaffold structures is an approach to promote the regeneration of articular cartilage while allowing for the repair of the underlying subchondral bone [ , ]. When bone marrow stromal cells GBMCs were cultured on these materials showed that the spongy structure with anisotropic porosity, adequate pore size and distribution with interconnectivity were supportive structure for cells to differentiate GBMCs into the chondrogenic lineage.
Fabrication of controlled design of such scaffolds play more important role from manipulation point of view and make them good promising tissue substitutes for the regeneration of osteochondral defects but it may not be adequately applicable for the repair of articular cartilage of large animal models [ ]. The results of histomorphologic and biochemical assays revealed neonatal cartilage-like tissue were generated which were similar to mature hyaline cartilage.
As mentioned previously, PVA is a high promising material for cartilage [ ] but its durability and week tissue adherent for a long term may not be ignored [ ]. It has been claimed that compositing PVA with a bioactive and biocompatible material such as hydroxyapatite could improve fixation ability of the scaffolds to the surrounded tissues [ , ]. Pan and Xiong [ ] have reported that the combination of PVA with hydroxyapatite can enhance not only mechanical properties and bioactivity but also adherent to around natural tissue [ ]; therefore the aforementioned problem of PVA was omitted.
The highly porous scaffolds possessed inter-connective pores structure assures morphological features necessary for regenerative medicine.
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These scaffolds possessed biphasic behavior, which showed articular cartilage behavior in the upper layer and bone behavior within the lower layer [ ]. Polylactide PLA is of biocompatible, biodegradable and renewable materials, which could be modified to enhance its biological properties for cartilage engineering applications [ ]. It is worthy of note that the presence of hydroxyapatite may balance the pH of the cell environment containing acidic degradation byproducts. However, the mechanical properties of the scaffolds have not been reported; however, this bioactive scaffold could promote the repair of full-thickness articular cartilage defects within three weeks and hyaline cartilage appearance with a columnar organization of cells and mature matrix was observed after six weeks [ 30 ].
There is an increasing need for novel materials with desired properties for tissue engineering and regenerative medicine. This review article outlined the significant studies that have been performed in cartilage tissue engineering especially articular cartilage. Recent progress in the preparation material blends natural-based and synthetic-based and nanocomposite, as well as fabrication porous scaffolds with tailored properties, in the field of articular cartilage tissue engineering have been discussed. Having advanced engineering approaches suggests combination of material and biological science as well as technology needed for preparation novel biomaterials and for designing and controlling the polymeric scaffolds for tissue repair as the synergistic combinations of material characteristics and scaffold design play critical roles in cell interaction, provide mechanical properties and then tissue regeneration.
A lot of research papers published regarding blends and composite materials for tissue engineering reveal there is a huge interest in this field; however most of results are far from clinical trials. In the near future, one can design multilayered biomaterial scaffolds, which may adequately mimic human articular cartilage tissue with respect to property and functionality of each zone while provides functional performance needed in long-term use with no sign of inflammation in vivo. Azadehsadat Hashemi Doulabi made substantial contributions to conception and acquisition of data, and analysis and interpretation of data, Kibret Mequanint participated in drafting the article and revising it critically for important intellectual content and Hadi Mohammadi gave final approval of the version to be submitted and any revised version.
Azadehsadat Hashemi Doulabi and Kibret Mequanint , analysis and interpretation of data: National Center for Biotechnology Information , U. Journal List Materials Basel v. Published online Jul Author information Article notes Copyright and License information Disclaimer. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license http: This article has been cited by other articles in PMC.
Abstract This review provides a comprehensive assessment on polymer blends and nanocomposite systems for articular cartilage tissue engineering applications. Introduction Polymeric materials are widely used in several biomedical fields. Table 1 List of some natural and synthetic polymers have been extensively surveyed for cartilage tissue engineering. Polymers Examples Natural polymers Proteins: Open in a separate window. Articular Cartilage Tissue Engineering 2. Structure-Property Relationships of Native Articular Cartilage In order to engineer articular cartilage; there is a need to understand its composition; architecture and function for identifying the essential requirements for matrixes or scaffolds used for this application; because the composition and structure of extracellular matrix ECM within this tissue has a direct role in its function as a mechanical surface through regulation of its tensile, shear and compressive properties [ 39 ].
Table 2 Mechanical properties of articular cartilage tissue regardless of location. Joint Disease and Medical Interventions There are different defects of articular cartilage with respect to the size, depth, and lesion locale including matrix disruption, partial-thickness and full-thickness [ 78 ]. Tissue Engineering of Cartilage and Scaffold Requirements Tissue engineering is a promising approach to repair or regenerate damaged tissues, organs with respect to recover them in the maximum efficiency with hopes of improving clinical outcomes.
Schematic representation of the articular tissue engineering procedure. Biomaterial Blends Polymer blending is a well-known technique whenever property modification is required, because this inexpensive technology enables materials with full set of tailored properties and improved specific properties [ ]. Table 3 Advantages and disadvantages of several natural and synthetic polymers have been extensively studied for cartilage tissue engineering, reprinted with permission from [ 6 ].
Polymers Disadvantages Advantages Chitosan Low tensile and compressive properties, low processability. Antibacterial activity, low toxicity, good cell interaction, good biocompatibility, renewability, water solubility, stability to variations of pH. Collagen Low tensile and compressive properties, high degradation rate. Low antigenicity, good cell adhesion, biological signaling, biodegradability. Hyaluronic acid Not support thermodynamically cell attachment. No immunogenicity, good cell interaction.
Alginates Hard processability, low tensile properties. Injectable polymers, easily crosslinking under mild condition, high and tunable porosity scaffold, high diffusion rates of macromolecules, good cell incorporation. FDA approval, easily processable.
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Polyurethane Acidic degradation byproducts in poly esther urethanes causing autocatalyzed degradation and in vivo inflammation. Good tensile and compressive properties and also biological properties such as cell attachment, incorporation and supporting chondrocyte phenotype, and low infection. PLGA Low biological properties such as cell attachment, incorporation and supporting chondrocyte phenotype, releasing acidic degradation byproducts caused inflammatory response.
FDA approval, tailorable physicomechanical properties. Blends with Collagen Among natural biomaterials, collagen has attracted many interests because it is the most abundant protein constituting the natural ECM of articular cartilage which is responsible for expressing the chondrocytes phenotype, maintaining GAG production and supporting the chondrogenesis [ 84 , ].
Biomaterial Nanocomposites Articular cartilage tissue shows unique combinations of nonlinear properties as well as anisotropic behaviors due to composition and orientation of tissue components [ 63 ]. Polymer-Polymer Nanofiber Composites It has been reported that ECM mimicry and maintenance of the chondrocytic phenotype are enhanced or promoted on the nanofiber scaffolds [ ]. Polymer-Silica Nanoparticle Composites Polymer-silica composites are another attractive class of materials for cartilage regeneration [ ]. Polymer-Hydroxyapatite Nanoparticle Composites Hydroxyapatite nanocomposites have been used in several application fields especially in bone tissue engineering [ ].
Conclusions There is an increasing need for novel materials with desired properties for tissue engineering and regenerative medicine. Author Contributions Azadehsadat Hashemi Doulabi made substantial contributions to conception and acquisition of data, and analysis and interpretation of data, Kibret Mequanint participated in drafting the article and revising it critically for important intellectual content and Hadi Mohammadi gave final approval of the version to be submitted and any revised version.
Conflicts of Interest The authors declare no conflict of interest. Polymeric biomaterials in tissue engineering. A critical review on polymer-based bio-engineered materials for scaffold development. Biodegradable polymer scaffolds to regenerate organs. Injectable biodegradable materials for orthopedic tissue engineering.
Synthetic biodegradable polymers as orthopedic devices. Polymeric materials for bone and cartilage repair. Cartilage tissue engineering for degenerative joint disease. Where we have been and where we are going. Chitosan, hyaluronan and chondroitin sulfate in tissue engineering for cartilage regeneration: Biodegradable synthetic polymers for tissue engineering.
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