Biomimetic protein‐based elastomeric hydrogels for biomedical applications

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

Novel polyurethane‐based thermosensitive hydrogels as drug release and tissue engineering platforms: design and in vitro characterization

Poloxamer P407 (P407) is a Food and Drug Administration approved triblock copolymer; its hydrogels show fast dissolution in aqueous environment and weak mechanical strength, limiting their in vivo application. In this work, an amphiphilic poly(ether urethane) (NHP407) was synthesized from P407, an aliphatic diisocyanate (1,6‐hexanediisocyanate) and an amino acid derived diol (N‐Boc serinol). NHP407 solutions in water‐based media were able to form biocompatible injectable thermosensitive hydrogels with a lower critical gelation temperature behavior, having lower critical gelation concentration (6% w/v versus 18% w/v), superior gel strength (G′ at 37 °C about 40 000 Pa versus 10 000 Pa), faster gelation kinetics (<5 min versus 15–30 min) and higher stability in physiological conditions (28 days versus 5 days) compared to P407 hydrogels. Gel strength and PBS absorption at 37 °C increased whereas dissolution rate (in phosphate‐buffered saline (PBS) at 37 °C) and permeability to nutrients (studied using fluorescein isothiocyanate–dextran model molecule) decreased as a function of NHP407 hydrogel concentration from 10% to 20% w/v. By varying the concentration, NHP407 hydrogels were thus prepared with different properties which could suit specific applications, such as in situ drug/cell delivery or bioprinting of scaffolds. Moreover, deprotected amino groups in NHP407 could be exploited for the grafting of bioactive molecules obtaining biomimetic hydrogels. © 2016 Society of Chemical Industry     

组织工程用水凝胶制备方法研究进展

高分子水凝胶作为-类重要的生物材料被广泛应用于生物医药和组织工程领域.本文综述了基于化学交联和物理交联的有关组织工程用水凝胶的设计方法,重点介绍了通过自由基共聚、结构互补基团间的化学反应、高能辐射和酶交联的化学交联型水凝胶以及通过离子间的相互作用,结晶作用、氢键及疏水性相互作用形成的物理交联型水凝胶的研究进展,对比了各种交联机制的优缺点,并对水凝胶在组织工程领域中的进-步应用进行了展望.     

PVA-based hydrogels for tissue engineering: A review

Poly (vinyl alcohol) (PVA) is a hydrophilic polymer with excellent biocompatibility and has been applied in various biomedical areas due to its favorable properties. PVA-based hydrogels have been recognized as promising biomaterials and suitable candidates for tissue engineering applications and can be manipulated to act various critical roles. However, due to some disadvantages (i.e., lack of cell-adhesive property), they needs further modification for desired and targeted applications. This review highlights recent progress in the design and fabrication of PVA-based hydrogels, including crosslinking and processing techniques. Finally, major challenges and future perspectives in tissue engineering are briefly discussed.     

A library of tunable agarose carbomer‐based hydrogels for tissue engineering applications: The role of cross‐linkers

The role of the crosslinking agents was studied for a series of agarose–carbomer‐based hydrogels, specifically developed for tissue engineering applications, and was quantified using the most typical polycondensation parameter; the ratio between the reacting moieties, i.e., hydroxyl (A) and carboxyl (B) groups. Because of the bonds among hydrophilic groups, as A/B ratio was increased, the gel network showed higher compactness and less ability to swell. The role of crosslinkers was also further analyzed using environmental scanning electron microscopy (E/SEM) and rheological measurements. SEM analysis underlined the presence of different structures as well as the erosion due to the presence of cosolvents in hydrogel synthesis. Rheological measurements showed the dependence of crossover strain value and yield stress upon the ratio of hydroxyl/carboxyl groups and, generally, a clear pseudoplastic behavior. Such detailed characterizations were essential to investigate the design of an optimized formulation capable of being a proper hosting environment for glial cells, which were here used as they are a promising cell type in several central nervous system repair strategies. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci 123:2211–2221, 2012     

Albumin-based biomaterial for lung tissue engineering applications

The role of albumin-based biomaterials in tissue engineering (TE) cannot be overemphasized. The authors review the role of albumin in lungs scaffold grafting, which promotes cell seeding. Albumin grafted on decellularized lungs scaffold is presented as a great support material for cell-tissue interaction as well as for ease in attachment, growth, and differentiation when seeded with different types of cells. Albumin scaffold fabrication from different sources is a promising approach that may facilitate medical treatments from bench-to-bed, although the role of this scaffold in lungs surfactant proteins regeneration and binding needs to be fully elucidated.     

Characterization and degradation behavior of agar-carbomer based hydrogels for drug delivery applications: solute effect

In this study hydrogels synthesized from agarose and carbomer 974P macromers were selected for their potential application in spinal cord injury (SCI) repair strategies following their ability to carry cells and drugs. Indeed, in drug delivery applications, one of the most important issues to be addressed concerns hydrogel ability to provide a finely controlled delivery of loaded drugs, together with a coherent degradation kinetic. Nevertheless, solute effects on drug delivery system are often neglected in the large body of literature, focusing only on the characterization of unloaded matrices. For this reason, in this work, hydrogels were loaded with a chromophoric salt able to mimic, in terms of steric hindrance, many steroids commonly used in SCI repair, and its effects were investigated both from a structural and a rheological point of view, considering the pH-sensitivity of the material. Additionally, degradation chemistry was assessed by means of infrared bond response (FT-IR) and mass loss.     

Synthesis and properties of carboxymethyl cellulose‐graft‐poly(acrylic acid‐co‐acrylamide) as a novel cellulose‐based superabsorbent

A new cellulose‐based superabsorbent polymer, carboxymethyl cellulose‐graft‐poly(acrylic acid‐co‐acrylamide), was prepared by the free‐radical grafting solution polymerization of acrylic acid (AA) and acrylamide (AM) monomers onto carboxymethyl cellulose (CMC) in the presence of N,N′‐methylenebisacrylamide as a crosslinker with a redox couple of potassium persulfate and sodium metabisulfite as an initiator. The influences of reaction variables such as the initiator content, crosslinker content, bath temperature, molar ratio of AA to AM, and weight ratio of the monomers to CMC on the water absorbency of the carboxymethylcellulose‐graft‐poly(acrylic acid‐co‐acrylamide) copolymer were investigated. The copolymer's structures were characterized with Fourier transform infrared spectroscopy. The optimum reaction conditions were obtained as follows: the bath temperature was 50°C; the molar ratio of AA to AM was 3 : 1; the mass ratio of the monomers to CMC was 4 : 1; and the weight percentages of the crosslinker and initiator with respect to the monomers were 0.75 and 1%, respectively. The maximum water absorbency of the optimized product was 920 g/g for distilled water and 85 g/g for a 0.9 wt % aqueous NaCl solution. In addition, the superabsorbent possessed good water retention and salt resistance. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1382–1388, 2007     

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     

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

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

Synthesis of chitosan beads as boron sorbents

Parameters, such as pH, temperature, initial boron concentration, adsorbent dosage, and ionic strength, affecting boron adsorption onto chitosan beads were examined in this study. The following values were obtained as the optimum conditions in our studied ranges: pH 8.0, temperature = 308 K, amount of chitosan beads = 0.15 g, initial boron concentration = 4 mg L⁻¹, and ionic strength = 0.1 M NaCl]. The adsorption kinetics were also examined in terms of three kinetic models: the pseudo‐first‐order, pseudo‐second‐order, and intraparticle diffusion models. The pseudo‐second‐order kinetic model showed very good agreement with the experimental data. Intraparticle plots seemed to have two steps and indicated multilinearity. Equilibrium data were evaluated with nonlinear and linear forms of the Langmuir and Freundlich equations. The experimental data conformed to the Freundlich equation on the basis of the formation of multilayer adsorption. To characterize the synthesized chitosan beads, we used Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) analyses. As shown by FTIR analysis, the boron species may have interacted with the NH₂ groups on chitosan. Microparticles of about 5 μm appeared in the SEM micrographs of the chitosan beads. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis and properties of silver nanoparticles in chitosan‐based thermosensitive semi‐interpenetrating hydrogels

In this article, thermosensitive poly(N‐isopropyl acrylamide‐co‐vinyl pyrrolidone)/chitosan [P(NIPAM‐co‐NVP)/CS] semi‐interpenetrating (semi‐IPN) hydrogels were prepared by redox‐polymerization using N,N‐methylenebisacrylamide as crosslinker and ammonium persulfate/N,N,N′,N′‐tetramethylethylenediamine as initiator. Highly stable and uniformly distributed Ag nanoparticles were prepared by using the semihydrogel networks as templates via in situ reduction of silver nitrate in the presence of sodium borohydride as a reducing agent. Introduction of CS improves the hydrogels swelling ratio (SR) and stabilizes the formed Ag nanoparticles in networks. Scanning electron microscopy and transmission electron microscopy revealed that Ag nanoparticles were well dispersed with diameters of 10 nm. The semi‐IPN hydrogel/Ag composites had higher SR and thermal stability than its corresponding semi‐IPN hydrogels. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

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

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

Oxygen‐releasing biomaterials for tissue engineering

Due to the increasing demand to generate thick and vascularized tissue‐engineered constructs, novel strategies are currently being developed. An emerging example is the generation of oxygen‐releasing biomaterials to tackle mass transport and diffusion limitations within engineered tissue constructs. Biomaterials containing oxygen‐releasing molecules can be fabricated in various forms, such as hybrid thin films, microparticles or three dimensional scaffolds. In this perspective, we summarize various oxygen‐releasing reagents and their potential applications in regenerative engineering. Moreover, we review the main approaches for fabricating oxygen‐releasing biomaterials for a range of tissue engineering applications. © 2013 Society of Chemical Industry     

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

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

Composite scaffolds for cartilage tissue engineering based on natural polymers of bacterial origin,thermoplastic poly(3‐hydroxybutyrate) and micro‐fibrillated bacterial cellulose

Cartilage tissue engineering is an emerging therapeutic strategy that aims to regenerate damaged cartilage caused by disease, trauma, ageing or developmental disorder. Since cartilage lacks regenerative capabilities, it is essential to develop approaches that deliver the appropriate cells, biomaterials and signalling factors to the defect site. Materials and fabrication technologies are therefore critically important for cartilage tissue engineering in designing temporary, artificial extracellular matrices (scaffolds), which support 3D cartilage formation. Hence, this work aimed to investigate the use of poly(3‐hydroxybutyrate)/microfibrillated bacterial cellulose (P(3HB)/MFC) composites as 3D‐scaffolds for potential application in cartilage tissue engineering. The compression moulding/particulate leaching technique employed in the study resulted in good dispersion and a strong adhesion between the MFC and the P(3HB) matrix. Furthermore, the composite scaffold produced displayed better mechanical properties than the neat P(3HB) scaffold. On addition of 10, 20, 30 and 40 wt% MFC to the P(3HB) matrix, the compressive modulus was found to have increased by 35%, 37%, 64% and 124%, while the compression yield strength increased by 95%, 97%, 98% and 102% respectively with respect to neat P(3HB). Both cell attachment and proliferation were found to be optimal on the polymer‐based 3D composite scaffolds produced, indicating a non‐toxic and highly compatible surface for the adhesion and proliferation of mouse chondrogenic ATDC5 cells. The large pores sizes (60 ‐ 83 µm) in the 3D scaffold allowed infiltration and migration of ATDC5 cells deep into the porous network of the scaffold material. Overall this work confirmed the potential of P(3HB)/MFC composites as novel materials in cartilage tissue engineering. © 2016 Society of Chemical Industry     

Interpenetrating networks hydrogels based on hyaluronic acid for drug delivery and tissue engineering

There are several techniques for preparing hydrogel biomaterials. Among these techniques, preparation of interpenetrating polymer networks hydrogel (IPNs) has been more interested during last years. IPNs are fabricated by the incorporation of monomers or polymeric chains in hydrogel network. Natural polymers such as hyaluronic acids have some advantages such as biocompatibility, biodegradability and non-toxicity. In this review, we would have a brief view to the interpenetrating polymer networks hydrogel based on hyaluronic acids and its applications as a drug delivery system and tissue engineering applications.     

Thiol–norbornene photoclick hydrogels for tissue engineering applications

Thiol–norbornene (thiol–ene) photoclick hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are crosslinked through light‐mediated orthogonal reactions between multifunctional norbornene‐modified macromers [e.g., poly(ethylene glycol) (PEG), hyaluronic acid, gelatin] and sulfhydryl‐containing linkers (e.g., dithiothreitol, PEG–dithiol, biscysteine peptides) with a low concentration of photoinitiator. The gelation of thiol–norbornene hydrogels can be initiated by long‐wave UV light or visible light without an additional coinitiator or comonomer. The crosslinking and degradation behaviors of thiol–norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned because of the orthogonal reactivity between norbornene and the thiol moieties. Uniquely, the crosslinking of step‐growth thiol–norbornene hydrogels is not oxygen‐inhibited; therefore, gelation is much faster and highly cytocompatible compared with chain‐growth polymerized hydrogels with similar gelation conditions. These hydrogels have been prepared as tunable substrates for two‐dimensional cell cultures as microgels and bulk gels for affinity‐based or protease‐sensitive drug delivery, and as scaffolds for three‐dimensional cell encapsulation. Reports from different laboratories have demonstrated the broad utility of thiol–norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas‐related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, and cancer cell biology. This article provides an up‐to‐date overview on thiol–norbornene hydrogel crosslinking and degradation mechanisms, tunable material properties, and the use of thiol–norbornene hydrogels in drug‐delivery and tissue engineering applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41563.     

Microstructure evolution of ammonia‐catalyzed phenolic resin during thermooxidative aging

The thermooxidative aging of ammonia‐catalyzed phenolic resin for 30 days at 60–170°C was investigated in this article. The aging mechanism and thermal properties of the phenolic resin during thermooxidative aging were described by thermogravimetry (TG)–Fourier transform infrared (FTIR) spectroscopy, attenuated total reflectance (ATR)–FTIR spectroscopy, and dynamic mechanical thermal analysis. The results show that the C? N bond decomposed into ammonia and the dehydration condensation between the residual hydroxyl groups occurred during the thermooxidative aging. Because of the presence of oxygen, the methylene bridges were oxidized into carbonyl groups. After aging for 30 days, the mass loss ratio reached 4.50%. The results of weight change at high temperatures coincided with the results of TG–FTIR spectroscopy and ATR–FTIR spectroscopy. The glass‐transition temperature (T_g) increased from 240 to 312°C after thermooxidative aging for 30 days, which revealed the postcuring of phenolic resins. In addition, an empirical equation between the weight change ratio and T_g was obtained. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012