Rapidly in situ forming adhesive hydrogel based on a PEG-maleimide modified polypeptide through Michael addition

Polyethylene glycol-maleimide modified ε-polylysine (EPL-PEG-MAL) with a unique comb-shaped structure was designed and used as a novel crosslinker for thiolated chitosan (CSS). Novel polysaccharide/polypeptide bionic hydrogels based on CSS and EPL-PEG-MAL could form rapidly in situ within 1 min via Michael addition under physiological conditions. Rheological studies showed that introduction of PEG can dramatically improve the storage modulus (G′) of the hydrogels and the optimal hydrogel system showed superior G′ of 1,614 Pa. The maximum adhesion strength reached 148 kPa, six times higher than that of fibrin glue. Cytotoxicity test indicated that the hydrogel is nontoxic toward growth of L929 cells. Gelation time, swelling ratio, storage modulus and adhesion strength of the hydrogels can be modulated by the content of PEG-maleimide, CSS concentration and molar ratio of maleimide group to thiol group. Benefiting from the fast gelation behaviors, desirable mechanical properties, relatively high adhesive performance and no cytotoxicity, these hydrogels have the potential applications as promising biomaterials for tissue adhesion and sealing.     

Synthesis and characterization of thermoresponsive shape-memory poly(stearyl acrylate-co-acrylamide) hydrogels

A novel series of thermoresponsive shape-memory copolymer hydrogels (poly(stearyl acrylate-co-acrylamide)) were synthesized by radical copolymerization of stearyl acrylate (SA) and acrylamide (AM). The chemical structure and crystal property of the poly(SA-co-AM) hydrogels were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimeter. The thermodynamic property of the hydrogels was studied by dynamic mechanical analysis. The swelling ratio and the shape recovery ratio of the hydrogels were also investigated. The results indicate that base on a reversible order–disorder transition, the large difference in storage modulus below and above the crystal melting temperature (T _m) of the poly(SA-co-AM) hydrogels. Furthermore, the prepared hydrogels can present excellent thermoresponsive shape-memory performance by changing the operation temperature below or above T _m, and the highest shape recovery ratio can reach 97%.     

Effects of chain length on oligopeptide hydrogelation

The co-assembly of mutually complementary, but self-repulsive oligopeptide pairs into viscoelastic hydrogels has been studied. Oligopeptides of 6, 10, and 14 amino acid residues were used to investigate the effects of peptide chain length on the structural and mechanical properties of the resulting hydrogels. Biophysical characterizations, including dynamic rheometry, small-angle X-ray scattering (SAXS) and fluorescence spectroscopy, were used to investigate hydrogelation at the bulk, fiber, and molecular levels, respectively. Upon mixing, the 10-mer peptides and the 14-mer peptides both form hydrogels while the 6-mer peptides do not. SAXS studies point to morphological similarity of the cross-sections of fibers underlying the 10:10 and 14:14 gels. However, fluorescence spectroscopy data suggest tighter packing of the amino acid side chains in the 10:10 fibers. Consistent with this tighter packing, dynamic rheometry data show that the 10:10 gel has much higher elastic modulus than the 14:14 mer (18 kPa vs. 0.1 kPa). Therefore, from the standpoint of mechanical strength, the optimum peptide chain length for this class of oligopeptide-based hydrogels is around 10 amino acid residues.     

细菌纤维素/聚谷氨酸复合水凝胶的辐照制备及性能

采用Co~(60)-γ射线辐照交联法制备细菌纤维素/聚谷氨酸(BC/PGA)复合水凝胶。采用红外光谱和扫描电子显微镜等对复合水凝胶的结构进行表征,研究了BC引入对复合水凝胶的凝胶分数、热失重、溶胀性能、压缩性能和流变性能的影响,并利用CCK-8法对复合水凝胶进行了细胞毒性评价。研究结果表明,辐照作用下BC纳米纤维和PGA形成双交联复合凝胶网络,BC可有效增加复合水凝胶的压缩强度、储能模量(G')和凝胶分数,降低复合水凝胶的平衡溶胀度。50kGy辐照剂量下,相对于纯PGA水凝胶,复合水凝胶压缩强度增大5倍,G'增大10倍。同时复合水凝胶无细胞毒性,可安全应用于生物医学领域。     

Curing kinetics and mechanical properties of a composite hydrogel for the replacement of the nucleuspulposus

A polymer material system has been developed to propose an injectable, UV and insitu curable hydrogel with properties similar to the native nucleuspulposus of intervertebral disc. Neat hydrogels based on Tween® 20 trimethacrylates (T3) and N-vinyl-2-pyrrolidone (NVP) and composite hydrogels of same composition reinforced by nano-fibrillated cellulose were synthesized with different T3 concentrations and their curing kinetics was investigated by photorheology using UV light. The T3 concentration has an influence on the time of curing and final shear stiffness of the material. NFC does not alter the time of curing but increases the final mechanical performance of the hydrogels for a same chemical composition. Hydrogel samples, neat and composite, were then tested in unconfined compression at different hydration stages and in confined compression and their elastic modulus was determined. The amount of fluid present in the network is mostly responsible for the mechanical properties and NFC fibres proved to be an efficient reinforcement. The elastic modulus ranged from 0.02 to 8 MPa. Biocompatibility studies showed that cells are confluent at 90% and do not show any morphology change when in contact with the hydrogel. The present hydrogel can therefore be considered for NP replacement.     

Swelling behavior and drug release of NIPAAm/PEGMEA copolymeric hydrogels with different crosslinkers

Poly(ethylene glycol) methylether acrylate (PEGMEA) and tetraethylene glycol diacrylate (TEGDA) were first synthesized. The thermosensitive hydrogels were then prepared from N-isopropylacrylamide (NIPAAm), PEGMEA, and three crosslinkers with different structures such as N, N′-methylene-bis-acrylamide (NMBA), TEGDA, and poly(ethylene glycol) dimethacrylate (EGDMA). The influence of polymerization factors such as the kind and amount of crosslinker and initial total monomer concentration on the swelling behavior, gel strength, effective crosslinking densities, and number-average molecular weight between crosslink points ( ) for the present copolymeric hydrogels was investigated. The results indicate that the swelling ratios for the present copolymeric gels decrease with increase in temperature. In addition, the results also showed that the higher swelling ratios for the present gels prepared from TEGDA were obtained due to the larger space between the gel networks. The crosslinking density depends on the swelling ratio and the kind and extent of crosslinker. In addition, the drug release behavior for the present copolymeric gels was investigated.     

Novel PEGylated pH-sensitive polymeric hollow microspheres

Novel PEGylated pH-sensitive poly[methacrylic acid-co-poly(ethylene glycol) methyl ether methacrylate] [P(MAA-co-PEGMA)] hollow microspheres were synthesized by a two-stage distillation precipitation polymerization. PMAA@P(MAA-co-PEGMA) core shell microspheres were synthesized by the second-stage polymerization of MAA and PEGMA, using the N,N′-methylenebisacrylamide (MBAAm) as crosslinker in the presence of non-crosslinked PMAA microspheres. The cavity was formed by selective removal of PMAA core in ethanol. The resulted PEGylated hollow microspheres were characterized with Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR). The shrink and swelling behavior under different pH was studied by Dynamic Light Scattering (DLS).     

Thermosensitive in situ-forming dextran–pluronic hydrogels through Michael addition

A thiolated dextran (Dex-SH) with a degree of substitution of 10 was synthesized and used for in situ hydrogel formation via Michael-type addition using vinyl sulfone functionalized Pluronic 127 (PL-VS) or acrylated Pluronic 127 (PL-Ar). Dextran/Pluronic hydrogels were rapidly formed in situ under physiological conditions upon mixing the solutions of Dex-SH and PL-VS or PL-Ar at a PL concentration of 10 or 20 w/v%. Rheological studies showed that these hydrogels with a broad range of storage moduli of 0.3 to 80 kPa could be obtained by varying PL concentration from 5% to 20 w/v%. Moreover, the hydrogels at a PL concentration of 10% or 20 w/v% revealed thermosensitive property with a temperature increase from 10 to 37 °C. Dex-SH/PL-Ar hydrogels were degradable under physiological conditions and had lower cytotoxicity than Dex-SH/PL-VS hydrogels. These thermosensitive injectable hydrogels show promise for biomedical applications.     

Development of a novel porous cryo-foam for potential wound healing applications

This body of work describes the development of a porous hydrogel for wound healing applications. In the present study poly (vinyl alcohol) (PVA) and poly (acrylic acid) (PAA) based hydrogels were prepared, and their properties were examined. Varying concentrations of the polymers and distilled water were used to prepare the hydrogels. The use of a high shear mixer, for foaming the PVA and PVA/PAA gels, and how this physical change can affect the structure and porosity of the hydrogel in question, represents a key feature of this work. The mechanical and thermal properties were determined by parallel plate rheometry and modulated differential scanning calorimetry (MDSC) respectively. The results indicated that the hydrogels containing low concentration of PVA and high volume of H₂O are significantly weaker than those synthesised with higher concentrations of PVA. The thermal analysis shows distinct endotherms and provides evidence of crystallisation. The chemical structure of the hydrogels was confirmed by means of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR).     

Polysaccharide-based magnetically responsive polyelectrolyte hydrogels for tissue engineering applications

Polysaccharide-based bionanocomposite hydrogels with functional nanomaterials were used in biomedical applications.Self-organization of xanthan gum and chitosan in the presence of iron oxide magnetic nanoparticles(Fe_3O_4MNPs)allowed us to form magnetically responsive polyelectrolyte complex hydrogels(MPECHs)via insitu ionic complexation using D-(+)-glucuronic acid?-lactone as a green acidifying agent.Characterization confirmed the successful formation of(and structural interactions within)the MPECH and good porous structure.The rheological behavior and compressive properties of the PECH and MPECH were measured.The results indicated that the incorporation of Fe_3O_4MNPs into the PECH greatly improved mechanical properties and storage modulus(G’).In vitro cell culture of NIH3T3 fibroblasts on MPECHs showed improvements in cell proliferation and adhesion in an external magnetic field relative to the pristine PECH.The results showed that the newly developed MPECH could potentially be used as a magnetically stimulated system in tissue engineering applications.     

The synthesis and degradation of collagenase-degradable poly(2-hydroxyethyl methacrylate)-based hydrogels and sponges for potential applications as scaffolds in tissue engineering

A collagenase-cleavable peptide-based crosslinking agent was synthesized and was incorporated into PHEMA sponges, and P[HEMA-co-MeO-PEGMA] gels and sponges [HEMA 2-hydroxyethyl methacrylate, PHEMA = poly(2-hydroxyethyl methacrylate), MeO-PEGMA = poly(ethylene glycol) monomethyl ether methacrylate]. PHEMA and P[HEMA-co-MeO-PEGMA] sponges had polymer droplet morphologies where the dimensions of the morphological features were three to five times larger compared to sponges that were crosslinked with tetraethylene glycol dimethacrylate (TEGDMA), while the P[HEMA-co-MeO-PEGMA] gels had similar morphologies regardless of the crosslinking agent. The differences in the dimensions of the morphologies of the sponges were attributed to differences in hydrophilicities of the crosslinking agent. When incubated in a collagenase solution, PHEMA sponges did not degrade, but P[HEMA-co-MeO-PEGMA] gels took 28 days to degrade and the P[HEMA-co-MeO-PEGMA] sponges took 101 days to degrade to 8% dry weight remaining. A cytotoxicity assay showed that the hydrogels do not elicit any cytotoxic response in vitro.     

In vitro release dynamics of thiram fungicide from starch and poly(methacrylic acid)-based hydrogels

In order to make the judicious use of pesticide/fungicide and to maintain the environment and ecosystem we have developed the starch and poly(methacrylic acid)-based agrochemical delivery system for their controlled and sustained release. The delivery device was prepared by using N,N'-methylenebisacrylamide (N,N'-MBAAm) as crosslinker and was characterized with FTIR, TGA and with swelling studies as a function of time and crosslinker concentration. This article discusses the swelling kinetics of polymer matrix and release dynamics of thiram (fungicide) from hydrogels for the evaluation of the diffusion mechanism and diffusion coefficients. The values of the diffusion exponent 'n' for both cases, that is the swelling of hydrogels and for the release of thiram from the hydrogels have been observed between 0.7 and 0.9 when the concentration of the crosslinker in the polymers were varied from 6.49x10(-3) to 32.43x10(-3) moles/L. It is inferred from the values of the 'n' that Non-Fickian diffusion mechanism has occurred in both the cases.     

Preparation of chitosan/mesoporous silica nanoparticle composite hydrogels for sustained co-delivery of biomacromolecules and small chemical drugs

Abstract

We have developed composite hydrogels of chitosan (CS) and mesoporous silica nanoparticles (MSNs) in this study. The gelation rate, gel strength, drug delivery behavior and chondrocyte proliferation properties were investigated. The introduction of MSNs into CS accelerated the gelation process at body temperature and also increased the elastic modulus G′ from 1000 to 1800 Pa. When we used gentamicin (GS) and bovine serum albumin (BSA) as model small chemical drugs and biomacromolecules, respectively, the CS/MSN hydrogels released GS and BSA in a sustained manner simultaneously, but the CS hydrogels only showed sustained BSA release. Furthermore, in vitro chondrocyte culture showed that the CS/MSN composite hydrogels indeed performed much better in supporting chondrocyte growth and maintaining chondrocytic phenotype compared to the CS hydrogels. Therefore, the results suggest that the CS/MSN composite hydrogels can be potentially very useful for cartilage regeneration.     

Composite gel-filled giant vesicles: Membrane homogeneity and mechanical properties

We further investigate the properties of composite Poly(NIPAM) (poly(N-isopropylacrylamide)) gel-filled giant vesicles, focusing here on i) the homogeneity of the membrane, ii) its coupling to the inner gel under strong suction pressures, and iii) the relation between the final elastic modulus of the vesicles and the amount of crosslinker in the pre-gel medium. We show that whereas the photo-polymerization process induces a decrease of the membrane homogeneity at the micrometer size range, the membrane still remains strongly coupled to the internal gel network. The vesicles studied here display average moduli in the range [0.5–25] kPa, confirming their potential as biomimetic mechanical systems.     

Influence of functionalization on properties of MWCNT-epoxy nanocomposites

The effects of various functionalized multi-walled carbon nanotubes (MWCNTs) on morphological, thermal, and mechanical properties of an epoxy based nanocomposite system were investigated. Chemical functionalization of MWCNT by oxidation (MWCNT-COOH) and direct-fluorination (MWCNT-F) were confirmed by FTIR, Raman spectroscopy, and TGA. Utilizing in situ polymerization, 1 wt% loading of MWCNT was used to prepare epoxy-based nanocomposites. Compared to the neat epoxy system, nanocomposites prepared with MWCNT-COOH showed 25.5% increase in ultimate flexural strength and 54.8% increase in flexural modulus. A decrease in strength was observed for the MWCNT-F nanocomposites. The premature degradation was attributed to a presumable catalyzation by hydrofluoric acid, HF, which evolved from the MWCNT-F during the curing process. However, only the MWCNT-F nanocomposites showed 22% increase in thermal properties (T_g). All nanophased systems showed increase in storage modulus.     

Synthesis and characterization of polycaprolactone/acrylic acid (PCL/AA) hydrogel for controlled drug delivery

In the present work biodegradable pH-sensitive polycaprolactone/acrylic acid (PCL/AA) hydrogels have been developed using ethylene glycol dimethacrylate (EGDMA) as a cross-linker and benzoyl peroxide as initiator. For these prepared hydrogels swelling studies, sol-gel fraction analysis and porosity measurements were performed. Results show that swelling of the hydrogels decreases on increasing the concentration of PCL and EGDMA, however swelling of hydrogels increases on increasing the concentration of AA. Results of sol-gel fraction analysis show that gel fraction increases on increasing concentration of monomer AA, polymer PCL as well as cross-linker EGDMA. As far as porosity is concerned, it increases on increasing the concentration of AA and PCL while porosity decreases on increasing the concentration of EGDMA. Hydrogels were characterized by measuring diffusion coefficient (D) and equilibrium water content (EWC). Network formation, morphology and crystallinity of PCL/AA hydrogels were investigated using FTIR, SEM and XRD, respectively. Tramadol hydrochloride was loaded as model drug and its release pattern was analysed using various kinetic models like zero order, first order, Higuchi and Peppas. Results indicated that most of the samples followed non-Fickian release mechanism.     

Magnetic PNIPA hydrogels for hyperthermia applications in cancer therapy

Temperature-sensitive Poly (N-isopropylacrylamide), PNIPA gels were synthesized with micron-sized iron and iron oxide (Fe₃O₄) particles to investigate their viability for combined hyperthermia and drug release applications. The ultimate goal is to combine hyperthermia and triggered drug release. Induction heating of the magnetic hydrogels with varying concentration of magnetic powder was conducted at a frequency of 375 kHz for magnetic field strength varying from 1.7 kA/m to 2.5 kA/m. It was observed that the maximum temperature induced in the magnetic hydrogels increased with the concentration of magnetic particles and magnetic field strength. The PNIPA gel underwent a collapse transition at 34 °C. The best combination was found for the PNIPA–Fe₃O₄ system, 2.5 wt.% Fe₃O₄ in PNIPA–Fe₃O₄ system took 260 s to be heated to 45 °C under a magnetic field strength of 1.7 kA/m and the specific absorption rate (SAR) was found to be 1.83. SAR of iron oxide was found to be higher than the SAR of iron.     

A smart hydrogel-based time bomb triggers drug release mediated by pH-jump reaction

Abstract

We demonstrate a timed explosive drug release from smart pH-responsive hydrogels by utilizing a phototriggered spatial pH-jump reaction. A photoinitiated proton-releasing reaction of o-nitrobenzaldehyde (o-NBA) was integrated into poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) (P(NIPAAm-co-CIPAAm)) hydrogels. o-NBA-hydrogels demonstrated the rapid release of protons upon UV irradiation, allowing the pH inside the gel to decrease to below the pK_a value of P(NIPAAm-co-CIPAAm). The generated protons diffused gradually toward the non-illuminated area, and the diffusion kinetics could be controlled by adjusting the UV irradiation time and intensity. After irradiation, we observed the enhanced release of entrapped L-3,4-dihydroxyphenylalanine (DOPA) from the gels, which was driven by the dissociation of DOPA from CIPAAm. Local UV irradiation also triggered the release of DOPA from the non-illuminated area in the gel via the diffusion of protons. Conventional systems can activate only the illuminated region, and their response is discontinuous when the light is turned off. The ability of the proposed pH-jump system to permit gradual activation via proton diffusion may be beneficial for the design of predictive and programmable devices for drug delivery.     

In situ ring-opening polymerization of hydroxyapatite/poly(ethylene adipate)-co-(ethylene terephthalate) biomimetic composites

Hydroxyapatite/poly(ethylene adipate)-co-poly(ethylene terephthalate) biomaterials (HAp/PEA-co-PET) have been prepared by ring opening polymerization (ROP) of cyclic oligo(ethylene adipate)-co-oligo(ethylene terephthalate) (C-OEA-co-C-OET) in the porous hydroxyapatite (HAp) scaffolds at 250 °C for 24 h under vacuum. The content of ROP-PEA-co-PET in the HAp/PEA-co-PET composite was about 20 wt% with the values of number average molecular weight $({\overline{M}_{{\rm n}}})$ and weight average molecular weight $({\overline{M}_{{\rm W}}})$ of 3380 and 7160 g/mol, respectively. Compressive strength and modulus of the HAp/PEA-co-PET composites were about 29 and 246 MPa, respectively. These mechanical properties were higher than those of the porous HAp templates and natural cancellous bone. In vitro bioactivity of the HAp/PEA-co-PET composites was studied by soaking in simulated body fluid (SBF) under the flowing system at the rate of 130 mL/day for 7, 14, 21 and 28 days. The formation of hydroxyapatite nanocrystals was observed on the composite surfaces through the consumption of calcium and phosphorus from the SBF solution, indicating the bioactivity of these HAp/PEA-co-PET composites. These results indicated the competency of HAp/PEA-co-PET composites for biomedical applications.     

Preparation and characterization of bio-nanocomposites based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and CoAl layered double hydroxide using melt intercalation

In this study, the exfoliated bio-nanocomposites based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3,4)HB) and cobalt-aluminum layered double hydroxide (LDH) were prepared via melt intercalation. The thermal stability, thermal combustion and thermo-mechanical properties for these bio-nanocomposites were systematically investigated. The formation of an exfoliated structure was confirmed by X-ray diffractometry and transmission electron microscopy analysis. The microscale combustion calorimetry results show that the heat release capacity (HRC) of the bio-nanocomposites is an important parameter of the fire hazard which is significantly reduced with the addition of LDH. The storage modulus of the bio-nanocomposites with small amount of LDH is remarkably enhanced measured by dynamic mechanical analysis.