Degradable natural polymer hydrogels for articular cartilage tissue engineering

Articular cartilage has poor ability to heal once damaged. Tissue engineering with scaffolds of polymer hydrogels is promising for cartilage regeneration and repair. Polymer hydrogels composed of highly hydrated crosslinked networks mimic the collagen networks of the cartilage extracellular matrix and thus are employed as inserts at cartilage defects not only to temporarily relieve the pain but also to support chondrocyte proliferation and neocartilage regeneration. The biocompatibility, biofunctionality, mechanical properties, and degradation of the polymer hydrogels are the most important parameters for hydrogel‐based cartilage tissue engineering. Degradable biopolymers with natural origin have been widely used as biomaterials for tissue engineering because of their outstanding biocompatibility, low immunological response, low cytotoxicity, and excellent capability to promote cell adhesion, proliferation, and regeneration of new tissues. This review covers several important natural proteins (collagen, gelatin, fibroin, and fibrin) and polysaccharides (chitosan, hyaluronan, alginate and agarose) widely used as hydrogels for articular cartilage tissue engineering. The mechanical properties, structures, modification, and structure–performance relationship of these hydrogels are discussed since the chemical structures and physical properties dictate the in vivo performance and applications of polymer hydrogels for articular cartilage regeneration and repair. © 2012 Society of Chemical Industry     

Influence of Process Variables on the Physical Properties of Gelatin/SA/HYA Composite Hydrogels

A novel composite hydrogel based on gelatin, sodium alginate (SA) and hyaluronic acid (HYA) was fabricated by freeze-drying method using 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide (EDC) as a cross-linker. The effects of chemical cross-linking, including cross-linker content and cross-linking time, on the morphology, swelling ratio and compressive strength of the gelatin/SA/HYA hydrogel were investigated. The influence of pH value of the swelling medium on the swelling ratio of the gelatin/SA/HYA composite hydrogel was also studied. The results showed that the gelatin/SA/HYA composite hydrogel had a three-dimensional interconnected structure and the pore size decreased with increasing EDC concentration. The IR absorption peak intensity of the gelatin/SA/HYA hydrogel has no obvious variety with increasing EDC content. The swelling ratio of the gelatin/SA/HYA hydrogel decreased with increasing cross-linker content and cross-linking time; however, the compressive strength increased with increasing EDC content and cross-linking time. The hydrogel swelling peak reached at pH 7. Therefore, the architecture and the physical properties of the gelatin/SA/HYA composite hydrogel can be adjusted by controlling the chemical cross-linking conditions and pH value of swelling medium.     

Ultrasonic monitoring of the network formation in superabsorbent cellulose based hydrogels

Biodegradable hydrogels are finding increasing interest in the academic and industrial field due to their high swelling capacity and the potential for many novel applications enabled by their biodegradability. The monitoring of the hydrogel cross-linking process is a crucial step for predicting hydrogel performances in terms of degree of swelling and viscoelastic properties.In this work, the chemical cross-linking of cellulose based hydrogels has been monitored during synthesis in water by means of ultrasonic wave propagation and low frequency dynamic mechanical analysis (DMA). The effect of the cross-linker concentration on the hydrogel acoustic behaviour has been also analysed and correlated with the different elastic response developed by the macromolecular hydrogel.The results demonstrate the reliability of the ultrasonic wave propagation in the following network formation process of a superabsorbent hydrogel, being capable of following the limited changes in the physical properties of the reacting solution.     

Anisotropic Chitosan Scaffolds Generated by Electrostatic Flocking Combined with Alginate Hydrogel Support Chondrogenic Differentiation

The replacement of damaged or degenerated articular cartilage tissue remains a challenge, as this non-vascularized tissue has a very limited self-healing capacity. Therefore, tissue engineering (TE) of cartilage is a promising treatment option. Although significant progress has been made in recent years, there is still a lack of scaffolds that ensure the formation of functional cartilage tissue while meeting the mechanical requirements for chondrogenic TE. In this article, we report the application of flock technology, a common process in the modern textile industry, to produce flock scaffolds made of chitosan (a biodegradable and biocompatible biopolymer) for chondrogenic TE. By combining an alginate hydrogel with a chitosan flock scaffold (CFS+ALG), a fiber-reinforced hydrogel with anisotropic properties was developed to support chondrogenic differentiation of embedded human chondrocytes. Pure alginate hydrogels (ALG) and pure chitosan flock scaffolds (CFS) were studied as controls. Morphology of primary human chondrocytes analyzed by cLSM and SEM showed a round, chondrogenic phenotype in CFS+ALG and ALG after 21 days of differentiation, whereas chondrocytes on CFS formed spheroids. The compressive strength of CFS+ALG was higher than the compressive strength of ALG and CFS alone. Chondrocytes embedded in CFS+ALG showed gene expression of chondrogenic markers (COL II, COMP, ACAN), the highest collagen II/I ratio, and production of the typical extracellular matrix such as sGAG and collagen II. The combination of alginate hydrogel with chitosan flock scaffolds resulted in a scaffold with anisotropic structure, good mechanical properties, elasticity, and porosity that supported chondrogenic differentiation of inserted human chondrocytes and expression of chondrogenic markers and typical extracellular matrix.     

辐射交联PVA/PVP/胶原复合水凝胶的制备及性能研究

采用辐射交联与冻融循环相结合的方法,将胶原引入聚乙烯醇(PVA)/聚乙烯基吡咯烷酮(PVP)水凝胶体系,制备具有较高生物活性的PVA/PVP/胶原复合水凝胶。通过含水率、溶胀性能、力学性能及微观结构研究胶原对复合水凝胶结构与性能的影响,并优选最佳体系进行体外细胞毒性实验(MTT法)。研究结果表明,复合水凝胶具有均匀分布的三维多孔结构,胶原的添加增大水凝胶网络空间结构,其初始含水率达92%,并在10 h内达到溶胀平衡,但力学性能降低。辐射交联与冻融循环相结合的方法有利于提高胶原水凝胶制备效率,胶原结构不改变,其体外细胞存活率从PVA/PVP水凝胶的77.3%提高到93.8%,细胞相容性提高。     

Mechanical and biological performance of rainbow trout collagen-boron nitride nanocomposite scaffolds for soft tissue engineering

We aim to investigate the potential of collagen extracted from rainbow trout for tissue engineering applications. In this regard, nanocomposite scaffolds based on the extracted collagen reinforced with various concentrations of boron nitride (BN) nanoparticles (0, 3, 6, 9, and 12 wt%) were developed. In addition, the role of various concentrations of BN nanoparticles and two-step cross-linking process on the physical and chemical properties of nanocomposite scaffolds were investigated. Our results demonstrated the isolation of Type I collagen with excellent thermal stability but with some structural and chemical differences compared to other sources. The synergic role of BN nanoparticles and two-step cross-linking process resulted in a noticeable improvement in the mechanical properties of collagen-BN scaffolds. Noticeably, incorporation of 6 wt% BN along with a two-step cross-linking process significantly increased the compressive strength (9.5 times) and elastic modulus (four times) of the collagen scaffold. Besides, nanocomposite scaffolds significantly improved proliferation and spreading of MG-63 cell line, confirming their biocompatibility. The results suggested that the incorporation of BN nanoparticles along with a two-step cross-linking process not only could promote the mechanical and thermal performances of collagen scaffolds, but also enhanced high cell viability, and proliferation supporting their potential in tissue engineering applications.     

Control of swelling properties of polyvinyl alcohol/hyaluronic acid hydrogels for the encapsulation of chondrocyte cells

Hydrogel scaffolds for tissue engineering are important biomaterials. The target in this study was to prepare polyvinyl alcohol/hyaluronic acid hydrogels for the encapsulation of chondrocyte cells by a simple cross‐linking reaction. Control of the swelling properties and morphology of the hydrogels for cultivation of chondrocytes was studied. The hydrogels were prepared from polyvinyl alcohol and hyaluronic acid derivatives bearing primary amine and aldehyde functionalities, respectively. The formation of the hydrogel upon mixing the aqueous solutions of the polymer derivatives took place at room temperature in a few seconds. The swelling properties of the hydrogels were found to depend on the polymer concentration and degree of substitution of the modified polymers. Scanning electron microscopy studies showed that the hydrogels had a suitable porous morphology for cell encapsulation. Furthermore, in vitro cell viability tests with the hydrogels showed no cytotoxicity for chondrocytes and that the cells grew well in the hydrogel scaffolds. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42272.     

Development of Biocompatible and Antibacterial Collagen Hydrogels via Dialdehyde Polysaccharide Modification and Tetracycline Hydrochloride Loading

Nowadays, collagen hydrogels with both good physicochemical and antibacterial properties for tissue engineering have drawn broad attention. Herein, a biocompatible and antibacterial collagen hydrogel is developed via alginate dialdehyde (ADA) modification and tetracycline hydrochloride (TC) loading based on Schiff's base formation. Fourier transform infrared spectroscopy and X‐ray diffraction spectra suggest the maintenance of collagen structure integrity after ADA modification. The modification significantly contributes to the improved swelling property, resistance against type I collagenase, and strengthens storage modulus of hydrogels with an increase of ADA concentrations. Meanwhile, dynamic release curves of tetracycline hydrochloride (TC)‐loaded hydrogels describe the burst release at the first 15 min then a gradual release, hydrogels act ideally as carriers in antibacterial activity. Furthermore, in vitro biocompatibility and antibacterial properties are successfully confirmed from the fabricated collagen hydrogels. This physicochemical‐ and antibacterial‐property–improved collagen hydrogel would be a potential candidate for wound healing as a scaffold.     

Chitosan hydrogel covalently crosslinked by gold nanoparticle: Eliminating the use of toxic crosslinkers

Tissue engineering has directed a lot of effort toward the development of devices with suitable biocompatibility and mechanical properties. Chitosan has been pointed as a valuable material to be applied in scaffolds due to its antimicrobial activity and biocompatibility. Nevertheless, the low mechanical resistance associated with the requirement of toxic crosslinkers has hampered translational application of chitosan hydrogel. Herein, the use of gold nanoparticles (AuNP) as crosslinker is reported as a great strategy to obtain chitosan hydrogel without using toxic reactants. In addition, the resultant chitosan hydrogel, crosslinked by AuNP of 30 nm (AuNP30), presented outstanding properties compared to chitosan hydrogel crosslinked by glutaraldehyde. Chitosan hydrogel crosslinked by AuNP30 presented lower porosity, which provided lower swelling degree and slower degradation rate. In addition, compressive strength was about two times higher than the chitosan hydrogel crosslinked by glutaraldehyde. The crosslink by AuNP30 also increased the biocompatibility of the hydrogel. Chitosan hydrogel crosslinked by AuNP30 did not show cytotoxicity against MEF cells, whereas cell viability of cells incubated with extract from chitosan hydrogel crosslinked by glutaraldehyde was only 41%. In conclusion, the results reported herein pointed that the use of AuNP30 as crosslinker agent provided to chitosan hydrogel enhanced properties that made it suitable to application in biomedical devices.     

Is Dialdehyde Chitosan a Good Substance to Modify Physicochemical Properties of Biopolymeric Materials?

The aim of this work was to compare physicochemical properties of three dimensional scaffolds based on silk fibroin, collagen and chitosan blends, cross-linked with dialdehyde starch (DAS) and dialdehyde chitosan (DAC). DAS was commercially available, while DAC was obtained by one-step synthesis. Structure and physicochemical properties of the materials were characterized using Fourier transfer infrared spectroscopy with attenuated total reflectance device (FTIR-ATR), swelling behavior and water content measurements, porosity and density observations, scanning electron microscopy imaging (SEM), mechanical properties evaluation and thermogravimetric analysis. Metabolic activity with AlamarBlue assay and live/dead fluorescence staining were performed to evaluate the cytocompatibility of the obtained materials with MG-63 osteoblast-like cells. The results showed that the properties of the scaffolds based on silk fibroin, collagen and chitosan can be modified by chemical cross-linking with DAS and DAC. It was found that DAS and DAC have different influence on the properties of biopolymeric scaffolds. Materials cross-linked with DAS were characterized by higher swelling ability (~4000% for DAS cross-linked materials; ~2500% for DAC cross-linked materials), they had lower density (Coll/CTS/30SF scaffold cross-linked with DAS: 21.8 ± 2.4 g/cm³; cross-linked with DAC: 14.6 ± 0.7 g/cm³) and lower mechanical properties (maximum deformation for DAC cross-linked scaffolds was about 69%; for DAS cross-linked scaffolds it was in the range of 12.67 ± 1.51% and 19.83 ± 1.30%) in comparison to materials cross-linked with DAC. Additionally, scaffolds cross-linked with DAS exhibited higher biocompatibility than those cross-linked with DAC. However, the obtained results showed that both types of scaffolds can provide the support required in regenerative medicine and tissue engineering. The scaffolds presented in the present work can be potentially used in bone tissue engineering to facilitate healing of small bone defects.     

PVA/Fe2O3磁敏感性水凝胶的制备及性能

采用循环冷冻-解冻方法制备了聚乙烯醇(PVA)/Fe2O3磁敏感性水凝胶. 考察了水凝胶的力学性能、溶胀性能和磁敏感性,并用扫描电镜观察了其表面形貌. 结果表明,当Fe2O3含量为1%(w)时,水凝胶的力学性能最好;水凝胶的溶胀度和脱水率随时间增加有相似的变化趋势,都随磁性粒子含量升高而降低;溶胀性能降低其交联程度增加;PVA和Fe2O3相容性较好;水凝胶在3000 Oe的磁场强度下达到饱和,呈现出很强的顺磁性,磁滞损耗较多,表明具有较好的磁敏感性.     

Alginate Based Scaffolds for Cartilage Tissue Engineering: A Review

Abstract

Many people, especially old and middle-aged, suffer from pain and disabilities caused by cartilage degradation. There are many surgical methods for cartilage treatment, however, none of them have shown acceptable results in long-term. Tissue engineering would be an acceptable approach for cartilage treatment. This includes cells, a carrier such as a matrix scaffold and signaling molecule. An ideal scaffold for cartilage tissue engineering should meet some requirements includes biocompatibility, biodegradability, and sufficient mechanical characteristic. While there are many suitable scaffolds made by natural and synthesis polymers, alginate- a natural polymer- has received good attention. Alginate offers many advantages for cartilage treatment; it has great potential in having tunable mechanical properties and easy manufacturing process. In the present paper, focusing on alginate as main scaffold constructive component, different studies on alginate based scaffolds in the form of physically, chemically and biologically crosslinked hydrogel, sponge, fiber, micro/nano particles and 3?D printed for articular cartilage tissue engineering are discussed and reviewed.     

碳纤维增强聚合物组织工程支架的制备及表征

以碳纤维（CF）作为增强材料,将CF有序排列于聚乳酸羟基乙酸（PLGA）多孔结构中,制备性能优良的CF/PLGA复合支架,并对其力学性能及细胞生物学性能进行表征.对增强体CF进行有序排列以提高支架的力学性能,扫描电子显微镜（SEM）观察CF/PLGA复合支架的微观形貌,可以看出CF在聚合物基体内部是呈有序结构并且二者结合情况良好.为了提高CF的生物相容性,利用对氨基苯甲酸对CF进行表面修饰,细胞生长在支架上的SEM照片反映了成纤维细胞对PLGA及CF/PLGA复合支架的黏附性能良好;通过细胞毒性测试,发现表面修饰的CF对细胞的生长没有负面作用,且在一定程度上促进了细胞的生长.研究结果表明,制备的CF/PLGA支架具有良好的力学性能和生物相容性,在骨组织工程支架的应用中具有一定的潜力.     

Synthesis and characterization of a dually crosslinked heparin-conjugated HA hydrogel for BMP-2 sustained delivery

A dually crosslinked heparin-conjugated hyaluronan hydrogel (DCH) was synthesized for reinforcement and sustainably delivering growth factors in tissue engineering. Heparin-conjugated hyaluronan microgels after glycidyl methacrylation as reinforcing phase crosslinked with glycidyl-methacrylated hyaluronan as matrix phase by ultraviolet radiation. The morphology, water swelling ratio, rheological property, degradation, bone morphogenetic protein-2 (BMP-2) loading and delivery, and cytotoxicity were characterized. Increasing heparin content enhanced the loading and sustainable delivery of BMP-2, but partly attenuated the mechanical property of DCH that presented a much higher elastic modulus than bulk gel. The incorporation of heparin and dually crosslinked network was harmless to the good cytocompatibility of hyaluronan hydrogel.     

Preparation and characterization of poly ε-caprolactone-gelatin/multi-walled carbon nanotubes electrospun scaffolds for cartilage tissue engineering applications

Abstract

Designing scaffolds with appropriate mechanical properties is a challenge in tissue engineering. In this study the poly ε-caprolactone (PCL)/gelatin with 1?wt.% of multi-walled carbon nanotubes (MWNTs) fabricated through electrospinning method. The presence of MWNTs led to an increase in the hydrophilicity and tensile strength, while maintaining an appropriate level of porosity percentage. The bioactivity and biodegradation evaluation demonstrated that the scaffolds containing MWNTs presented more bioactivity and slower degradation rate. Cell culture study showed that the nanocomposite scaffolds did not have any cytotoxicity. According to the results, the PCL-gelatin/MWNTs nanocomposite scaffold can be appropriate for cartilage tissue engineering applications.     

羟丙基壳聚糖/氧化甲基纤维素自愈合水凝胶的制备及其载药性能

采用高碘酸钠对甲基纤维素（MC）进行氧化制备了氧化甲基纤维素（DAMC），通过羟丙基壳聚糖（HPC）的氨基与DAMC的醛基发生希夫碱反应制备了HPC/DAMC自愈合水凝胶。通过调节HPC和DAMC含量探究水凝胶的微观形态、溶胀性能、力学性能、自愈合性能、体外降解以及药物缓释性能。结果表明，HPC/DAMC自愈合水凝胶具有相互连通的孔隙，且孔径处于80～375μm范围内，在室温无刺激条件下能够在20 min内实现自愈合且具有良好的拉伸性能。此外，HPC/DAMC自愈合水凝胶具有良好的保水性，其溶胀比为14.0～17.4。在溶菌酶的作用下，HPC/DAMC自愈合水凝胶在60 h时质量损失率可达84.2%～99.6%。HPC/DAMC自愈合水凝胶对抗肿瘤药物吉西他滨具有缓释效果，缓释作用长达96 h，药物累积释放率达到83.2%～92.7%。     

Exploring the dual role of α,ω-di-carboxylic acids in the preparation of collagen based biomaterial

Di-carboxylic acids (DCAs), a precursor for many polyamides and polyester preparations, may also find applications in the preparation of high-performance biopolymer material for tissue engineering research. In the present study, collagen, a natural biopolymer when mixed with the chosen DCAs, through ionic interaction between R–COO^? and –NH₃ ⁺, dissolution as well as stabilization of collagen was achieved, which obviates the use of carbodiimide activation of –COOH groups of DCA. The DCA engineered collagen biopolymer material obtained in the form of 3D scaffolds was subjected to evaluate its high performance through in vitro and in vivo studies. Results on FT-IR, CD, TGA, DSC, SEM, mechanical properties, docking simulation studies and binding energy calculations explored the interactions and the in vitro cytotoxicity assays and in vivo wound healing studies explored and authenticated the performance of the DCA engineered biopolymer material and suggested the option for tissue engineering research.     

Synthesis and cytocompatibility of collagen/hydroxyapatite nanocomposite scaffold for bone tissue engineering

Collagen/hydroxyapatite nanocomposite scaffolds were prepared by in situ precipitation and freeze‐drying approach. The synthesized collagen/hydroxyapatite nanocomposites were characterized using various modalities. It was revealed that the inorganic phase in the nanocomposite was carbonate‐substituted hydroxyapatite with low crystallinity. Morphology studies showed the uniform distribution of hydroxyapatite particles in the collagen hydrogel. In addition, hydroxyapatite particles were gradually becoming irregular enough and the surface morphology had more wrinkles with the increase of inorganic component. Morphology, mechanical properties and cell biocompatibility of the prepared nanocomposite scaffolds were evaluated. The scaffolds presented a well‐developed macropore structure with a pore size ranging from 100 to 200 μm and the pore size of scaffold can also be regulated by changing the organic/inorganic weight ratio. Furthermore, the growth of MG63 cells on scaffolds showed they could significantly promote the proliferation of cells and could be potential candidate for bone engineering applications. POLYM. COMPOS., 81–90, 2016. © 2014 Society of Plastics Engineers     

High strength and bioactivity polyvinyl alcohol/collagen composite hydrogel with tannic acid as cross-linker

Hydrogels have great potential applications in biomedical materials, but their applications in complex physiological environments are severely limited by their weak strength and biotoxicity. Generally, synthetic polymer hydrogels and natural polymer hydrogels have complementary advantages in terms of mechanical strength and biological activity. Herein, tannic acid (TA), a natural material, was introduced into the polyvinyl alcohol/collagen (PVA-COL) double network to prepare a hydrogel (PVA-COL-TA) with good bioactivity and mechanical properties. The tensile strength of the composite hydrogel can reach up to 20 times that of the pure PVA hydrogel. And the hydrogel after swelling under physiological conditions also exhibits stable mechanical properties. The introduction of TA can reduce the degradation rate of COL, enabling it to continue to exert biological activity. in vitro cytocompatibility experiments showed that PVA-COL-TA hydrogel has good sustained biological activity and the potential for biomedical materials.     

三甲基壳聚糖季铵盐水凝胶的制备及性能

采用反应活性强和交联条件温和的二乙烯基砜为交联剂,制备了N,N,N-三甲基壳聚糖季铵盐水凝胶（TMCG）并研究了TMCG的溶胀行为、水的状态和分布以及力学性能等。结果表明,TMCG在水中溶胀迅速,平衡溶胀度达40倍,并且具有离子响应性;水分子在TMCG中以自由水、可冻结的结合水和非冻结的结合水三种形式存在,其非冻结的结合水含量随交联剂浓度的增加而增大。TMCG具有良好的力学性能,拉伸强度达13.8 MPa,断裂伸长率达135.3%。