Inadequate self-repair and regenerative efficiency of the cartilage tissues has motivated the researchers to devise advanced and effective strategies to resolve this issue. Introduction of bioprinting to tissue engineering has paved the way for fabricating complex biomimetic engineered constructs. In this context, the current review gears off with the discussion of standard and advanced 3D/4D printing technologies and their implications for the repair of different cartilage tissues, namely, articular, meniscal, nasoseptal, auricular, costal, and tracheal cartilage. The review is then directed towards highlighting the current stem cell opportunities. On a concluding note, associated critical issues and prospects for future developments, particularly in this sphere of personalized medicines have been discussed.
Far-flung evolution in tissue engineering enabled the development of bioactive and biodegradable materials to generate biocomposite nanofibrous scaffolds for bone repair and replacement therapies. Polymeric bioactive nanofibers are to biomimic the native extracellular matrix (ECM), delivering tremendous regenerative potentials for drug delivery and tissue engineering applications. It's been known from few decades that Zinc oxide (ZnO) nanoparticles are enhancing bone growth and providing proliferation of osteoblasts when incorporated with hydroxyapatite (HAp). We attempted to investigate the interaction between the human foetal osteoblasts (hFOB) with ZnO doped HAp incorporated biocomposite poly(L-lactic acid)-co-poly(ε-caprolactone) and silk fibroin (PLACL/SF) nanofibrous scaffolds for osteoblasts mineralization in bone tissue regeneration. The present study, we doped ZnO with HAp (ZnO(HAp) using the sol-gel ethanol condensation technique. The properties of PLACL/SF/ZnO(HAp) biocomposite nanofibrous scaffolds enhanced with doped and blended ZnO/HAp were characterized using Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Contact angle and Tensile studies to determine the morphology, functionality, wettability and stability. The in vitro study results showed that the addition of ZnO and HAp enhances the secretion of bone mineral matrix (98%) with smaller fiber diameter (139.4 ± 27 nm) due to the presence of silk fibroin showing potential tensile properties (322.4%), and increased the proliferation of osteoblasts for bone tissue regeneration.
In this work, the novel imprinted zeolite (IZ) was synthesized, and its properties and performance in terms of adsorption of p-Cresol, which represent the protein-bounded uremic toxins in aqueous phase under phosphate buffer saline, were studied and compared with the synthesized zeolite-Y (ZeoY-S) and commercial CBV 100 zeolite-Y (ZeoY-C). The ZeoY-S was synthesized from sodium aluminate, NaOH, H2O and SiO2 under aging for 24 h at room temperature and hydrothermal condition for 24 h at 100 °C, with an initial composition of 10SiO2:Al2O3:4Na2O:180H2O. The ZeoY-S has been modified by using the imprinting technology to produce the IZ via the use of p-Cresol as a template. The p-Cresol successfully imprinted on the zeolite-Y was proved through the multipoint Brunauer-Emmett-Teller (BET) and the performance of IZ that was compared to ZeoY-S and ZeoY-C. Based on the BET results, it proves that the pore size of IZ is in accordance with the target compound, which is p-Cresol at 0.79 nm. This modification was able to adsorb p-Cresol 2.5 and 3.5 times higher than ZeoY-S and ZeoY-C can, respectively. Langmuir and Freundlich adsorption isotherm models, together with the pseudo-first and -second order and intra-particle diffusion kinetics models, were used to investigate the adsorption behavior of p-Cresol on the zeolites. The IZ has 4.30 times greater competitive molecules than ZeoY-S and the properties of IZ were not influenced by the content of other phenolic group uremic toxins as competitive molecules. It can be concluded that the micropores of zeolite as adsorbent can be modified using the imprinting technology in order to increase its sensitivity and selectivity towards p-Cresol.
Polymer-clay based nanocomposites are among the attractive materials to be applied for various applications, including biomedical. The incorporation of the nano sized clay (nanoclay) into polymer matrices can result in their remarkable improvement in mechanical, thermal and barrier properties as long as the nanofillers are well exfoliated and dispersed throughout the matrix. In this work, exfoliation strategy through pre-dispersing process of the organically modified montmorillonite (organo-MMT) nanofiller was done to obtain ethyl vinyl acetate (EVA) nanocomposite with improved flexibility, toughness, thermal stability and biostability. Our results indicated that the degree of organo-MMT exfoliation affects its cytotoxicity level and the properties of the resulting EVA nanocomposite. The pre-dispersed organo-MMT by ultrasonication in water possesses higher degree of exfoliation as compared to its origin condition and significantly performed reduced cytotoxicity level. Beneficially, this nanofiller also enhanced the EVA flexibility, thermal stability and biostability upon the in vitro exposure. We postulated that these were due to plasticizing effect and enhanced EVA-nanofiller interactions contributing to more stable chemical bonds in the main copolymer chains. Improvement in copolymer flexibility is beneficial for close contact with human soft tissue, while enhancement in toughness and biostability is crucial to extend its life expectancy as insulation material for implantable device.
Hydroxyapatite (HA) coated implant is more susceptible to bacterial infection as the micro-structure surface which is beneficial for osseointegration, could also become a reservoir for bacterial colonisation. The aim of this study was to introduce the antibacterial effect of silver (Ag) to the biomineralised HA by utilising a polydopamine film as an intermediate layer for Ag and HA immobilisation. Sufficient catechol groups in polydopamine were required to bind chemically stainless steel 316 L, Ag and HA elements. Different amounts of Ag nanoparticles were metallised on the polydopamine grafted stainless steel by varying the immersion time in silver nitrate solution from 12 to 24 h. Another polydopamine layer was then formed on the metallised film, followed by surface biomineralisation in 1.5 Simulated Body Fluid (SBF) solution for 3 days. Several characterisation techniques including X-Ray Photoelectron Spectroscopy, Atomic Force Microscopy, Scanning Electron Microscopy and Contact Angle showed that Ag nanoparticles and HA agglomerations were successfully immobilised on the polydopamine film through an element reduction process. The Ag metallisation at 24 h has killed the viable bacteria with 97.88% of bactericidal ratio. The Ag was ionised up to 7 days which is crucial to prevent bacterial infection during the first stage of implant restoration. The aged functionalised films were considered stable due to less alteration of its chemical composition, surface roughness and wettability properties. The ability of the functionalised film to coat complex and micro scale metal make it suitable for dental and orthopaedic implants application.
Antibacterial coating is important to prevent the colonization of medical devices by biofilm forming bacteria that would cause infection and sepsis in patients. Current coating techniques such as immobilization of antimicrobial compounds, time-releasing antibiotic agents and silver nanoparticles, require multiple processing steps, and they have low efficacy and low stability. We proposed a single-step plasma polymerization of an essential oil known as carvone to produce a moderately hydrophobic antibacterial coating (ppCar) with an average roughness of <1nm. ppCar had a static water contact angle of 78°, even after 10days of air aging and it maintained its stability throughout 24h of LB broth immersion. ppCar showed promising results in the live-dead fluorescence assay and crystal violet assay. The biofilm assay showed an effective reduction of E. coli and S. aureus bacteria by 86% and 84% respectively. ppCar is also shown to rupture the bacteria membrane for its bactericidal effects. The cytotoxicity test indicated that the coating is not cytotoxic to the human cell line. This study would be of interest to researcher keen on producing a bacteria-resistance and biocompatible coating on different substrates in a cost-effective manner.
Dental implants made of pure titanium suffer from abrasion and scratch during routine oral hygiene procedures. This results in an irreversible surface damage, facilitates bacteria adhesion and increases risk of peri-implantitis. To overcome these problems, titanium nitride (TiN) coating was introduced to increase surface hardness of pure titanium. However, the osteoconductivity of TiN is considered to be similar or superior to that of titanium and its alloys and therefore surface modification is necessary. In this study, TiN coating prepared through gas nitriding was partially oxidized by hydrothermal (HT) treatment and ozone (O3) treatment in pure water to improve its osteoconductivity. The effects of HT treatment and O3 treatment on surface properties of TiN were investigated and the osteoconductivity after undergoing treatment was assessed in vitro using osteoblast evaluation. The results showed that the critical temperature for HT treatment was 100°C since higher temperatures would impair the hardness of TiN coating. By contrast, O3 treatment was more effective in oxidizing TiN surfaces, improving its wettability while preserving its morphology and hardness. Osteoblast attachment, proliferation, alkaline phosphatase (ALP) expression and mineralization were improved on oxidized specimens, especially on O3 treated specimens, compared with untreated ones. These effects seemed to be consequences of partial oxidation, as well as improved hydrophilicity and surface decontamination. Finally, it was concluded that, partially oxidized TiN is a promising coating to be used for dental implant.
Localised and targeted potential of nanocarrier for the eminent anticancer agent paclitaxel (PTX) could provide a great platform towards improvement of efficacy with reduction in associated toxicities, whereas incorporation of TPGS could further facilitate delivery in MDR through alteration of its inherent physicochemical properties. Current article therefore puts into perspective on nanocarrier-based recent researches of PTX with special stress towards TPGS-nanoparticle-mediated delivery in the improvement of cancer treatment and then accompanied with the discussion on distinct influence of the fabrication process. Such dynamic fabrications of the nanoparticulate therapy stimulate cellular interaction with frontier area for future research in tumor targeting potential.
Collagen is the most abundant extracellular matrix (ECM) protein in the human body, thus widely used in tissue engineering and subsequent clinical applications. This study aimed to extract collagen from ovine (Ovis aries) Achilles tendon (OTC), and to evaluate its physicochemical properties and its potential to fabricate thin film with collagen fibrils in a random or aligned orientation. Acid-solubilized protein was extracted from ovine Achilles tendon using 0.35M acetic acid, and 80% of extracted protein was measured as collagen. SDS-PAGE and mass spectrometry analysis revealed the presence of alpha 1 and alpha 2 chain of collagen type I (col I). Further analysis with Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) confirms the presence of triple helix structure of col I, similar to commercially available rat tail col I. Drying the OTC solution at 37°C resulted in formation of a thin film with randomly orientated collagen fibrils (random collagen film; RCF). Introduction of unidirectional mechanical intervention using a platform rocker prior to drying facilitated the fabrication of a film with aligned orientation of collagen fibril (aligned collagen film; ACF). It was shown that both RCF and ACF significantly enhanced human dermal fibroblast (HDF) attachment and proliferation than that on plastic surface. Moreover, cells were distributed randomly on RCF, but aligned with the direction of mechanical intervention on ACF. In conclusion, ovine tendon could be an alternative source of col I to fabricate scaffold for tissue engineering applications.
Polyethersulfone (PES) based membranes are used for dialysis, but exposure to blood can result in numerous interactions between the blood elements and the membrane. Adsorption and transformation of plasma proteins, activation of blood cells, adherence of platelets and thrombosis reactions against PES membrane can invoke severe blood reactions causing the increase rate of mortality and morbidity of hemodialysis (HD) patients. In order to minimize blood immune response, different biomimetic, zwitterionic, non-ionic, anticoagulant molecules and hydrophilic brushes were immobilized or blended with PES polymers. These additives modified the nature of the membrane, enhanced their biocompatibility and also increased the uremic waste dialysis properties. In this review, current perspectives of the different additives which are used with PES are highlighted in relation with PES membrane-associated blood reactions. The additive's purpose, compatibility, preparation techniques, methods of addition to polymer and influence on the chemistry and performance of hemodialysis membranes are described.
In spite of antibiotics, antibacterial agents or specifically known as antiseptics are actively explored for the prevention of infection-associated medical devices. Antibacterial agents are introduced to overcome the complication of bacterial resistance which devoted by antibiotics. It can be classified into inorganic and organic, that prominently have impacted bacterial retardation in their own killing mechanism patterns. Therefore, this review paper aimed to provide information on most common used inorganic and organic antibacterial agents which have potential to be utilized in biomedical applications, thus, classifying the trends of antibacterial mechanism on Gram-negative and Gram-positive bacteria. In the beginning, infectious diseases and associated biomedical infections were stated to expose current infection scenarios on medical devices. The general view, application, susceptible bacteria and activation mechanism of inorganic (silver, copper, gold and zinc) and organic (chlorhexidine, triclosan, polyaniline and polyethylenimine) antibacterial agents that are widely proposed for biomedical area, were then gathered and reviewed. In the latter part of the study, the intact mechanisms of inorganic and organic antibacterial agents in retarding bacterial growth were classified and summarized based on its susceptibility on Gram-negative and Gram-positive bacteria. Most of inorganic antibacterial agents are in the form of metal, which release its ions to retard prominently Gram-negative bacteria. While organic antibacterial agents are susceptible to Gram-positive bacteria through organelle modification and disturbance of bio-chemical pathway. However, the antibacterial effects of each antibacterial agent are also depending on its effective mechanism and the species of bacterial strain. These compilation reviews and classification mechanisms are beneficial to assist the selection of antibacterial agents to be incorporated on/within biomaterials, based on its susceptible bacteria. Besides, the combination of several antibacterial agents with different susceptibilities will cover a wide range of antibacterial spectrum.
Tissue engineering (TE) is an advanced principle to develop a neotissue that can resemble the original tissue characteristics with the capacity to grow, to repair and to remodel in vivo. This research proposed the optimization and development of nanofiber based scaffold using the new mixture of maghemite (γ-Fe2O3) filled poly-l-lactic acid (PLLA)/thermoplastic polyurethane (TPU) for tissue engineering heart valve (TEHV). The chemical, structural, biological and mechanical properties of nanofiber based scaffold were characterized in terms of morphology, porosity, biocompatibility and mechanical behaviour. Two-level Taguchi experimental design (L8) was performed to optimize the electrospun mats in terms of elastic modulus using uniaxial tensile test where the studied parameters were flow rate, voltage, percentage of maghemite nanoparticles in the content, solution concentration and collector rotating speed. Each run was extended with an outer array to consider the noise factors. The signal-to-noise ratio analysis indicated the contribution percent as follow; Solution concentration>voltage>maghemite %>rotating speed>flow rate. The optimum elastic modulus founded to be 28.13±0.37MPa in such a way that the tensile strain was 31.72% which provided desirability for TEHV. An empirical model was extracted and verified using confirmation test. Furthermore, an ultrafine quality of electrospun nanofibers with 80.32% porosity was fabricated. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and cell attachment using human aortic smooth muscle cells exhibited desirable migration and proliferation over the electrospun mats. The interaction between blood content and the electrospun mats indicated a mutual adaption in terms of clotting time and hemolysis percent. Overall, the fabricated scaffold has the potential to provide the required properties of aortic heart valve.
This paper presents the fabrication of a highly sensitive and selective glucose sensor based on cuprous oxide/graphene nanocomposites-modified glassy carbon electrode (Cu2O/graphene/GCE). The Cu2O/graphene nanocomposites were synthesized based on a simple and straightforward chemical reduction process in alkaline aqueous solution using sodium carbonate as reductant. The size and shape of Cu2O nanoparticles on graphene sheets can be controlled by changing the amount of graphene oxide added during reaction. The electrochemical properties of Cu2O/graphene/GCE in 0.1M phosphate buffer solution were investigated by cyclic voltammetry and electrochemical impedance spectroscopy. It was found that the pH, concentration of supporting electrolyte, and scan rate had very crucial effect on the sensitivity of prepared sensor towards glucose oxidation. At an applied potential of +0.50V, the Cu2O/graphene/GCE presented a high sensitivity of 1330.05μAmM(-1)cm(-2) and fast response (within 3s). The amperometric non-enzymatic glucose sensor developed had a linear relationship from 0.01mM to 3.0mM glucose and detection limit of 0.36μM. In the presence of ascorbic acid, uric acid, dopamine, chloride and citrate ion and other carbohydrates, the interferences were negligible. The proposed sensor was successfully applied for the determination of glucose concentration in real human blood samples.
Novel biosensor architecture based on nanocrystalline cellulose (NCC)/CdS quantum dots (QDs) nanocomposite was developed for phenol determination. This nanocomposite was prepared with slight modification of nanocrystalline cellulose (NCC) with cationic surfactant of cetyltriammonium bromide (CTAB) and further decorated with 3-mercaptopropionic acid (3-MPA) capped CdS QDs. The nanocomposite material was then employed as scaffold for immobilization of tyrosinase enzyme (Tyr). The electrocatalytic response of Tyr/CTAB-NCC/QDs nanocomposite towards phenol was evaluated using differential pulse voltammetry (DPV). The current response obtained is proportional to the concentration of phenol which attributed to the reduction of o-quinone produced at the surface of the modified electrode. Under the optimal conditions, the biosensor exhibits good linearity towards phenol in the concentration range of 5-40 μM (R2 = 0.9904) with sensitivity and limit of detection (LOD) of 0.078 μA/μM and 0.082 μM, respectively.
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become a threat to global health because of limited treatments. MRSA infections are difficult to treat due to increasingly developing resistance in combination with protective biofilms of Staphylococcus aureus (S. aureus). Nanotechnology-based research revealed that effective MRSA treatments could be achieved through targeted nanoparticles (NPs) that withstand biological films and drug resistance. Thus, the principal aim towards improving MRSA treatment is to advance drug delivery tools, which successfully address the delivery-related problems. These potential delivery tools would also carry drugs to the desired sites of therapeutic action to overcome the adverse effects. This review focused on different types of nano-engineered carriers system for antimicrobial agents with improved therapeutic efficacy of entrapped drugs. The structural characteristics that play an essential role in the effectiveness of delivery systems have also been addressed with a description of recent scientific advances in antimicrobial treatment, emphasizing challenges in MRSA treatments. Consequently, existing gaps in the literature are highlighted, and reported contradictions are identified, allowing for the development of roadmaps for future research.
Vaginal drug delivery is regarded as a promising route against women-related health issues such as unwanted pregnancies and sexually transmitted infections. However, only a very few studies have been reported on the use of hydrogel rings with low cytotoxicity for vaginal drug delivery applications. Moreover, the effect of nanoparticles on hydrogel vaginal rings has not been clearly evaluated. To overcome these challenges, we hereby developed nanocomposite hydrogel rings based on polyacrylamide-sodium carboxymethyl cellulose-montmorillonite nanoparticles in the ring-shaped aluminum mold for controlled drug delivery. The hydrogel rings were synthesized by using N,N'-methylene bisacrylamide, N,N,N',N'-tetramethyl ethylene diamine, and ammonium persulfate, as a crosslinker, accelerator, and initiator, respectively. The obtained rings were 5.5 cm in diameters and 0.5 cm in rims. Chemical structures of the nanocomposite rings were confirmed by Fourier transform infrared, and Nuclear Magnetic Resonance spectroscopies. Additionally, the swelling ratio of hydrogels was appeared to be adjusted by the introduction of nanoparticles. In vitro release experiment of methylene blue, as a hydrophilic model drug, revealed that the nanocomposite rings could not only reduce burst effect (almost more than twice), but also achieve prolonged release for 15 days in the vaginal fluid simulant which mimic the vaginal conditions at pH of almost 4.2, and a temperature of 37 °C. Importantly, the resultant hydrogel rings with or without various concentrations of montmorillonite showed low cytotoxicity toward human skin fibroblasts. Furthermore, different antibacterial activities against Escherichia coli were observed for various concentrations of montmorillonite in hydrogels. These results suggest the great potential of montmorillonite-based hydrogel rings for vaginal drug delivery.
Cleft palate is a congenital malformation that generates a maxillofacial bone defect around the mouth area. The creation of performance scaffolds for bone tissue engineering in cleft palate is an issue that was proposed in this research. Because of its good biocompatibility, high stability, and non-toxicity, silk fibroin was selected as the scaffold of choice in this research. Silk fibroin scaffolds were prepared by freeze-drying before immerging in a solution of collagen, decellularized pulp, and collagen/decellularized pulp. Then, the immersed scaffolds were freeze-dried. Structural organization in solution was observed by Atomic Force Microscope (AFM). The molecular organization of the solutions and crystal structure of the scaffolds were characterized by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD), respectively. The weight increase of the modified scaffolds and the pore size were determined. The morphology was observed by a scanning electron microscope (SEM). Mechanical properties were tested. Biofunctionalities were considered by seeding osteoblasts in silk fibroin scaffolds before analysis of the cell proliferation, viability, total protein assay, and histological analysis. The results demonstrated that dendrite structure of the fibrils occurred in those solutions. Molecular organization of the components in solution arranged themselves into an irregular structure. The fibrils were deposited in the pores of the modified silk fibroin scaffolds. The modified scaffolds showed a beta-sheet structure. The morphological structure affected the mechanical properties of the silk fibroin scaffolds with and without modification. Following assessment of the biofunctionalities, the modified silk fibroin scaffolds could induce cell proliferation, viability, and total protein particularly in modified silk fibroin with collagen/decellularized pulp. Furthermore, the histological analysis indicated that the cells could adhere in modified silk fibroin scaffolds. Finally, it can be deduced that modified silk fibroin scaffolds with collagen/decellularized pulp had the performance for bone tissue engineering and a promise for cleft palate treatment.
Copper(II) complex of quercetin Cu+Q, mixed ligand complexes, quercetin-Cu(II)-phenanthroline [Cu+Q(PHt)] and quercetin-Cu(II)-neocuproine [Cu+Q(Neo)] have been synthesized and characterized. From the FT-IR spectroscopic studies, it was evident that C-ring of quercetin is involved in the metal chelation in all the three copper complexes. C-ring chelation was further proven by UV-Visible spectra and the presence of Cu(II) from EPR spectroscopic investigations. These complexes were found to have osteogenic and angiogenic properties, observed through in vitro osteoblast differentiation and chick embryo angiogenesis assay. In osteoblast differentiation, quercetin-Cu(II) complexes treatment increased calcium deposition and alkaline phosphatase activity (ALP) activity at the cellular level and stimulated Runx2 mRNA and protein, ALP mRNA and type 1 collagen mRNA expression at the molecular level. Among the complexes, Q+Cu(PHt) showed more effects on osteoblast differentiation when compared to that of other two copper complexes. Additionally, Q+Cu(Neo) showed more effect compared to Q+Cu. Furthermore, the effect of these complexes on osteoblast differentiation was confirmed by the expression of osteoblast specific microRNA, pre-mir-15b. The chick embryo angiogenesis assay showed that angiogenic parameters such as blood vessel length, size and junctions were stimulated by these complexes. Thus, the present study demonstrated that quercetin copper(II) complexes exhibit as a pharmacological agent for the orthopedic application.
Hydroxyapatite is used extensively in hard tissue repair due to its biocompatibility and similarity to biological apatite, the mineral component of bone. It differs subtly in composition from biological apatite which contains other ions such as magnesium, zinc, carbonate and silicon (believed to play biological roles). Traditional methods of hydroxyapatite synthesis are time consuming and require strict reaction parameter control. This paper outlines synthesis of magnesium substituted hydroxyapatite using simple microwave irradiation of precipitated suspensions. Microwave irradiation resulted in a drastic decrease in ageing times of amorphous apatitic phases. Time taken to synthesize hydroxyapatite (which remained stable upon heat treatment at 900°C for 1h) reduced twelve folds (to 2h) as compared to traditionally required times. The effects of increasing magnesium concentration in the precursors on particle size, surface area, phase-purity, agglomeration and thermal stability, were observed using scanning electron microscopy, BET surface area analysis, X-ray diffraction and photo acoustic Fourier transform infra-red spectroscopy. Porous agglomerates were obtained after a brief heat-treatment (1h) at 900°C.
The mechanical, thermal, and morphological properties of a 3D porous Pennisetum purpureum (PP)/polylactic acid (PLA) based scaffold were investigated. In this study, a scaffold containing P. purpureum and PLA was produced using the solvent casting and particulate leaching method. P. purpureum fibre, also locally known as Napier grass, is composed of 46% cellulose, 34% hemicellulose, and 20% lignin. PLA composites with various P. purpureum contents (10%, 20%, and 30%) were prepared and subsequently characterised. The morphologies, structures and thermal behaviours of the prepared composite scaffolds were characterised using field-emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The morphology was studied using FESEM; the scaffold possessed 70-200μm-sized pores with a high level of interconnectivity. The moisture content and mechanical properties of the developed porous scaffolds were further characterised. The P. purpureum/PLA scaffold had a greater porosity factor (99%) and compression modulus (5.25MPa) than those of the pure PLA scaffold (1.73MPa). From the results, it can be concluded that the properties of the highly porous P. purpureum/PLA scaffold developed in this study can be controlled and optimised. This can be used to facilitate the construction of implantable tissue-engineered cartilage.