Thermosensitive Composite Hydrogels Research Articles

Temperature-sensitive hydrogel dressing loaded with nicotinamide mononucleotide accelerating wound healing in diabetic mice

Diabetic foot ulcers, a common complication of diabetes mellitus, significantly impact patients’ quality of life and impose a substantial economic burden on healthcare systems. However, the currently used treatments are associated with various challenges and the traditionally used dressings lack functional efficacy. Oxidative stress is believed to play a vital role in diabetic wound healing. Therefore, nicotinamide mononucleotide (NMN), which is known for its antioxidant properties, offers the potential to accelerate the wound-healing process. Here, a thermosensitive composite hydrogel was synthesized by mixing Pluronic F127 and Pluronic F68 with an antibacterial component chitosan. The hydrogel exhibited favorable properties including a stable structure, appropriate solid–liquid phase change, loose porosity, slow-release, antibacterial properties, and biocompatibility. In vitro experiments demonstrated that the NMN-loaded temperature-sensitive hydrogel effectively promoted cell proliferation, migration, and angiogenesis and exhibited antioxidant activity. In diabetic thickness skin defect models, NMN-loaded temperature-sensitive hydrogel treatment significantly accelerated wound healing by promoting collagen synthesis, angiogenesis, and increased expression of vascular endothelial growth factor and transforming growth factor- β1. In summary, NMN-loaded temperature-sensitive hydrogel can promote diabetic wound healing in a simple, economical, effective, and safe manner, with potential application in treating diabetic wounds.

Construction of chitosan-based thermosensitive composite hydrogels for recognizing and combined chemo-photodynamic elimination of Gram-negative bacterial infections

Recently, rapid acquisition of bacterial resistance and consequent slow healing of infected wounds threaten human life and health. In this study, chitosan-based hydrogels and nanocomplexes ZnPc(COOH)8:PMB composed of photosensitizer ZnPc(COOH)8 and antibiotic polymyxin B (PMB) were integrated into a thermosensitive antibacterial platform ZnPc(COOH)8:PMB@gel. Interestingly, fluorescence and reactive oxygen species (ROS) of ZnPc(COOH)8:PMB@gel can be triggered by E. coli bacteria at 37 °C, but not by S. aureus bacteria, which gave the potential to simultaneously detect and treat Gram-negative bacteria. The survival rate for a certain amount of E. coli bacteria treated with ZnPc(COOH)8:PMB (ZnPc(COOH)8 2 μM) was decreased by approximately fivefold than that with either ZnPc(COOH)8 or PMB alone, indicating combined antibacterial efficacy. ZnPc(COOH)8:PMB@gel facilitated the complete healing of wounds infected with E. coli bacteria in about seven days, while over 10 % wounds treated with ZnPc(COOH)8 or PMB remained unhealed on the 9th day. ZnPc(COOH)8:PMB resulted in a threefold increase of ZnPc(COOH)8 fluorescence in E. coli bacteria suggesting enhanced uptake of ZnPc(COOH)8 for the intervention of PMB on membrane permeability. The construction principle of the thermosensitive antibacterial platform and the combined antimicrobial strategy can be applied to other photosensitizers and antibiotics for detection and treatment of wound infections.

Basic fibroblast growth factor/chitosan derivatives/collagen composite thermosensitive hydrogel promotes perio-dontal tissue regeneration in rats.

To investigate the feasibility of different thermosensitive composite hydrogels from chitosan derivatives as scaffold materials for periodontal tissue engineering. Three chitosan derivatives with different biological characteristics were prepared, namely, sulfonated chitosan (SCS), phosphorylated chitosan (PCS), and phosphorylated sulfonated chitosan (PSCS). Three thermosensitive composite hydrogels were constructed using basic fibroblast growth factor (bFGF), the chitosan derivatives, and collagen. Twenty male Wistar rats were randomly divided into control group, blank group, bFGF/SCS/collagen composite thermosensitive hydrogel group, bFGF/PCS/collagen compo-site thermosensitive hydrogel group, and bFGF/PSCS/collagen composite thermosensitive hydrogel group. Then, three-wall intrabony defects were established. The defects were treated with the different kinds of thermosensitive composite hydrogels. After 6 weeks of surgery, the animals were killed, and specimens were collected. Then, gross observation, hematoxylin-eosin staining, and Masson staining were performed. The bFGF/chitosan derivatives/collagen composite thermosensitive hydrogel groups and the control group had statistical differences in the relative alveolar bone height, relative epithelial down growth and grading count score of periodontal tissue regeneration (P<0.05). bFGF/chitosan derivatives/collagen composite thermosensitive hydrogels have good application prospects in periodontal tissue engineering.

Spontaneous coal combustion prevention mechanisms of thermosensitive composite hydrogel: An experimental study

This study aims to determine the prevention mechanisms of spontaneous coal combustion in thermosensitive composite hydrogels. A thermosensitive composite hydrogel is prepared using methylcellulose, polyethylene glycol, and sodium chloride. A self-designed fire extinguishing experimental device is used to test the inhibitory effects of the thermosensitive composite hydrogel on spontaneous coal combustion. Changes in the water loss rate of the hydrogel under different temperature conditions are also studied. The surface morphology and pore structure of the thermosensitive composite hydrogel are observed by scanning electron microscopy. Finally, the characteristics of the functional groups during the combustion of the coal samples are analysed using a Fourier transform infrared spectrometer. The results show that the thermosensitive composite hydrogel undergoes a phase transformation at temperatures above 58 °C. When the coal sample temperature reaches 200 °C, the cooling and suffocation effects of the hydrogel are optimal because the water loss rate of the hydrogel exceeds 50 %. Furthermore, the hydrogel is firmly coated on the surface of the coal body to prevent any contact between coal and oxygen. In addition, the thermosensitive composite hydrogel generates a strong dehydrating agent and inert gas after thermal decomposition. The collision between gas products and free radicals reduces the effective collision probability between the coal surface active molecules and oxygen, further inhibiting spontaneous coal combustion. These results provide a basis for the practical application of thermosensitive composite hydrogels in underground mines, and guidance for the research and development of thermosensitive composite hydrogel materials.

Ionic liquid decorated MXene/Poly (N-isopropylacrylamide) composite hydrogel with high strength, chemical stability and strong adsorption

Organic phenolic pollutants in industrial wastewater cause severe environmental pollution and physiological damage. Poly (N-isopropylacrylamide) (PNIPAM) hydrogels generally have poor mechanical strength and are also intrinsically frangible, limiting their widespread applications in wastewater treatment. Combining them with 2-dimensional materials can also only improve the mechanical properties of hydrogels. Here, we report a high-strength, chemical stability and strong adsorption MXene/poly (N-isopropylacrylamide) (PNIPAM) thermosensitive composite hydrogel for efficient removal of phenolic pollutants from industrial wastewater. Ionic liquids (ILs) were grafted onto the surface of MXenes and introduced into NIPAM monomer solution to obtain composite hydrogels by in-situ polymerization for improved mechanical strength and adsorption capacity of the composite hydrogel. Compared with the MXene/PNIPAM composite hydrogel, the introduction of ILs simultaneously improves the mechanical and adsorption properties of the composite hydrogel. The ILs bind to the surface of MXene flakes through electrostatic interactions, which improved the thermal stability and oxidation resistance of MXenes while maintaining its good dispersion. Using 1-Ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF4) modified MXene (MXene-EMIMBF4) did not change significantly were observed after aging for 45 days. As-prepared composite hydrogels demonstrated excellent mechanical properties, reusability, and high adsorption capacity for p-Nitrophenol (4-NP). The MXene-EMIMBF4/PNIPAM hydrogel could recover after ten 95% strain compression cycles under the synergistic effect of chemical bonding and electrostatic attraction. Its maximum adsorption capacity for 4-NP was 200.29mgg-1 at room temperature, and the adsorption capacity maintained at ∼90% of its initial value after five adsorption cycles, which was related to the introduction of EMIMBF4 to form a denser network structure. The adsorption data followed the pseudo-second-order kinetics and Freundlich models.

In situ subcutaneously injectable thermosensitive PEG-PLGA diblock and PLGA-PEG-PLGA triblock copolymer composite as sustained delivery of bispecific anti-CD3 scFv T-cell/anti-EGFR Fab Engager (BiTEE)

In this study, PEGylated poly (lactide-co-glycolide) (PLGA) thermosensitive composite hydrogels (DTgels) loaded with bispecific anti-cluster of differentiation 3 (CD3) scFv T-cell/anti-epidermal growth factor receptor (EGFR) Fab engager (BiTEE) were subcutaneously (s.c.) injected for the in situ formation of a drug deposit to resolve limitations of the clinical application of the BiTEE of a short half-life and potential side effects. Three kinds of DTgels prepared with different ratios of methoxy poly (ethylene glycol) (mPEG)-PLGA (diblock copolymer, DP) and PLGA-PEG-PLGA (triblock copolymer, TP) were designated DTgel-1, DTgel-2, and DTgel-2S. All three DTgel formulations showed thermosensitive properties with a sol-gel transition temperature at 28–34 °C, which is suitable for an injection. An in vitro release study showed that all DTgel formulations loaded with stabilized BiTEE extended the release of the BiTEE for up to 7 days. In an animal pharmacokinetics study, an s.c. injection of BiTEE/DTgel-1, BiTEE/DTgel-2, or BiTEE/DTgel-2S respectively prolonged the half-life of the BiTEE by 3.5-, 2.0-, and 2.2-fold compared to an intravenous injection of the BiTEE solution. Simultaneously, BiTEE/DTgel formulations showed almost no proinflammatory cytokine release in mice injected with T cells after s.c. administration. Results of an animal antitumor (MDA-MB-231) study indicated that an s.c. injection of the BiTEE/DTgel formulations significantly improved the antitumor efficacy compared to an intravenous (i.v.) or s.c. injection of the BiTEE solution. Moreover, BiTEE/DTgel formulations led to enhanced T-cell recruitment to solid-tumor sites. In conclusion, the in situ formation of injectable PEGylated PLGA thermosensitive hydrogels loaded with the BiTEE was successfully carried out to increase its half-life, maintain a constant blood level within therapeutic windows, and enhance T-cell recruitment to solid-tumor sites resulting in exceptional treatment efficacy.

Facile Synthesis of Thermo-Sensitive Composite Hydrogel with Well Dispersed Ag Nanoparticles for Application in Superior Antibacterial Infections.

In this study, we have described a facile process for fabrication of multifunctional composite hydrogel, in which sodium alginate was subjected to cross-linking using Ca2+ derived from ZnO/CaCO₃/Ag composite nanospheres. The ZnO/CaCO₃/Ag composite nanospheres were prepared based on our previously reported AA-[Zn(OH)₄]2- composite nanosphere reaction conducted with silver and calcium salt following hydrothermal method, that led to the disintegration and release of Ca2+ under acidic conditions for application as a cross-linking agentto catalyze reaction with sodium alginate. Ag nanoparticles were well-dispersed in the multifunctional composite hydrogel, exhibiting excellent antibacterial activity. Additionally, polydopamine (PDA) with photothermal effect was also added to obtain a multifunctional composite hydrogel, and this hydrogel showed photothermal conversion performance and facilitated the release of Ag+ to achieve the rapid antibacterial effect. Simultaneously, PDA NPs could scavenge free radicals and improve cell adhesion. All such features would promote wound healing. The potent antimicrobial activity of the prepared composite hydrogel was demonstrated in the mouse model of S. aureus infection, and biosafety of the hydrogel was confirmed by conducting histopathological examination in the mouse model. This type of multifunctional hydrogel wound dressing with photosensitive and antibacterial properties presents with broad applications and prospects in antibacterial treatment.

An oxygen-enriched thermosensitive hydrogel for the relief of a hypoxic tumor microenvironment and enhancement of radiotherapy

The rapid proliferation of tumor cells and tortuous vasculature in solid tumors often bring about a hypoxic tumor microenvironment, which renders tumor cells more resistant to many cancer treatments, including radiotherapy. In this study, an injectable and thermosensitive composite hydrogel composed of perfluorooctanoic acid (PFOA) modified monomethoxy poly(ethylene glycol)-poly(D,L-lactide-co-glycolide) (mPEG-PLGA-PFOA) and perfluorooctyl bromide (PFOB) that presented a thermoreversible sol-gel transition upon heating was developed to deliver exogenous oxygen for the relief of tumor hypoxia and enhancement of radiotherapy. The fluorinated modification of copolymers significantly increased the stability of PFOB in the mPEG-PLGA-PFOA aqueous solution owing to the fluorophilic interaction between PFOB and PFOA-modified copolymers. The introduction of PFOB not only efficiently heightened the oxygen loading capacity of the composite hydrogel, but also endowed it with excellent X-ray opacity, allowing the visual observation of the hydrogel via micro-CT imaging. After peritumoral injection of the oxygen-enriched composite hydrogel, the continuous supply of oxygen effectively relieved tumor hypoxia and down-regulated the expression of hypoxia-inducible factor-1α. Profiting from this, the hyposensitivity of tumor cells to radiation was successfully reversed, and the tumor growth in mice was significantly suppressed and the survival of mice was prolonged when combined with multiple X-ray exposure. As a result, the oxygen-enriched composite hydrogel shows a great potential for radiosensitization to improve the radiotherapeutic efficacy.

An injectable photothermally active antibacterial composite hydroxypropyl chitin hydrogel for promoting the wound healing process through photobiomodulation.

Prevention of bacterial infection, acceleration of wound closure and promotion of skin regeneration are crucial in the wound healing process. In this work, the photothermal activity of an injectable thermosensitive composite hydrogel based on hydroxypropyl chitin (HPCH), tannic acid (TA) and ferric ions (Fe3+) was studied. It was found that the photothermal efficiency was enhanced when the molar ratio of Fe3+/TA increased up to 20. The composite hydrogel possessed good cytocompatibility and hemocompatibility with a low dosage of the antibacterial agent TA. In vitro and in vivo antibacterial tests showed that the HPCH/TA/Fe hydrogel possessed an effective and rapid bactericidal effect with 10 minutes of near-infrared laser irradiation. Furthermore, the combination of a low-level laser therapy with the hydrogel is conducive to the acceleration of wound closure and promotion of skin tissue repair. Thus, the injectable photothermally active antibacterial composite hydrogel has great potential for the infected skin wound regeneration in clinical applications.

Thermosensitive composite hydrogel incorporated with curcumin-loaded nanopolymersomes for prolonged and localized treatment of glioma

In the current study, in order to augment the therapeutic efficacy of curcumin, thermo-sensitive biodegradable hydrogel composed of poly (ε-caprolactone-co-lactide)-b-poly (ethylene glycol)-b-poly (ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) incorporating curcumin-loaded polyethylene glycol-b-polylactide (mPEG-PLA) nanopolymersome was prepared. The final objective of this study was to introduce a biodegradable thermo-responsive, injectable hydrogel that can prolong and localize therapeutic effects of curcumin. The obtained results demonstrated that the encapsulation of curcumin nanopolymersome in the thermos-sensitive hydrogel provided the sustained controlled release of the encapsulated curcumin. The rheological investigation demonstrated that the viscosity of the prepared composite hydrogel (20% copolymer solution) was low which made it intratumorally injectable. However, at physiological temperature (37 °C), system was in gel state with good mechanical strength thereby providing sustained release of the encapsulated platform upon intratumoral administration. In vivo administration of the prepared composite hydrogel incorporating curcumin nanopolymersome to ectopic C6 glioma tumor model in nude mice illustrated ideal therapeutic response of the prepared composite platform.The key innovation of the current study was the development of biodegradable, injectable therapeutic-loaded implant to improve the outcomes of glioma treatment while reducing the treatment complications.

A chitosan-based thermosensitive scaffold loaded with bone marrow-derived mesenchymal stem cells promotes motor function recovery in spinal cord injured mice

Spinal cord injury is a devastating trauma with high mortality and disability, for which there is no effective treatment. Stem cell-based tissue engineering has been reported to promote functional neural recovery. At present, building a neural scaffold with excellent biocompatibility for cells and tissues is still challenging. In this study, a new thermosensitive composite hydrogel based on chitosan, hydroxyethyl cellulose, collagen and β-phosphoglycerate (CS-HEC-Col/GP hydrogel) is developed to encapsulate murine bone marrow-derived mesenchymal stem cells (BMSCs) to improve therapeutic efficacy in spinal cord injured mice. This composite hydrogel possesses a good cytocompatibility to mouse BMSCs by live/dead staining, minimized inflammatory reaction in vivo by hematoxylin and eosin staining and suitable rheological behavior similar to neural tissue, ranging from 100 to 1000 Pa. Furthermore, the data from animal experiments indicated that BMSC-loaded CS-HEC-Col/GP hydrogel could enhance the survival or proliferation of endogenous nerve cells, probably by secreting neurotrophic factors and inhibiting apoptosis, and thereby promote the recovery of motor function in the hindlimbs of a murine spinal cord injury model.

Chitosan-based thermosensitive composite hydrogel enhances the therapeutic efficacy of human umbilical cord MSC in TBI rat model

Recently, stem cell–based therapy shows great promise in treating traumatic brain injury. However, the low rate of cell engraftment and survival are two major barriers for efficacy. To improve the therapeutic effect, a new thermosensitive hydrogel based on chitosan, hydroxyethyl cellulose, hyaluronic acid, and β-glycerophosphate (CS-HEC-HA/GP) was developed in this study. This CS-HEC-HA/GP hydrogel exhibits a faster gelation process and better biocompatibility to human umbilical cord mesenchymal stem cells (hUC-MSC) versus CS/GP or CS-HEC/GP hydrogels. The suitable rheological behavior similar to brain tissue supports that the CS-HEC-HA/GP hydrogel might be a preferable neural scaffold. In addition, CS-HEC-HA/GP hydrogel loaded with hUC-MSC could enhance the retention, survival, and migration of encapsulated hUC-MSC, improve survival and proliferation of endogenous neural cells probably by secreting neurotrophic factors and inhibiting apoptosis, and thereby accelerate remodeling of brain structure and neurological function recovery in TBI rats. Thus, this hydrogel shows enormous potentials in stem cell–based neural tissue repair and regeneration.

Injectable chitosan/gelatin/bioactive glass nanocomposite hydrogels for potential bone regeneration: In vitro and in vivo analyses.

The present work describes in vitro and in vivo behaviors of thermosensitive composite hydrogels based on polymers/bioactive glass nanoparticles. Assays in SBF (simulated body fluid) solution showed that loss of hydrogel mass in vitro was decreased by 4.3% when bioactive glass nanoparticles (nBG) were incorporated, and confirmed the bioactivity of nBG containing hydrogels. In vitro assays demonstrated the cytocompatibility of the hydrogels with encapsulated rat bone marrow mesenchymal stem cells (BMSC). Crystal violet assays showed a 27% increase in cell viability when these cells were seeded in hydrogels containing nBG. In vivo biocompatibility was examined by injecting hydrogels into the dorsum of Swiss rats. The results indicated that the prepared hydrogels were nontoxic upon subcutaneous injection, and could be candidates for a safe in situ gel-forming system. Injection of the hydrogels into a rat tibial defect allowed preliminary evaluation of the hydrogels' regenerative potential. Micro Computed Tomography analysis suggested that more new tissue was formed in the defects treated with the hydrogels. Taken together, our data suggest that the developed injectable composite hydrogels possess properties which make them suitable candidates for use as temporary injectable matrices for bone regeneration.

Regenerated Antheraea pernyi Silk Fibroin/Poly(N-isopropylacrylamide) Thermosensitive Composite Hydrogel with Improved Mechanical Strength.

At present, Antheraea pernyi silk fibroin (ASF) has attracted research efforts to investigate it as a raw material for fabrication of biomedical devices because of its superior cytocompatibility. Nevertheless, native ASF is not easily processed into a hydrogel without any crosslinking agent, and a single hydrogel shows poor mechanical properties. In this paper, a series of ASF/poly (N-isopropylacrylamide) (PNIPAAm) composite hydrogels with different ASF contents were manufactured by a simple in situ polymerization method without any crosslinking agent. Meanwhile, the structures, morphologies and thermal properties of composite hydrogels were investigated by XRD, FTIR, SEM, DSC and TGA, respectively. The results indicate that the secondary structure of silk in the composite hydrogel can be controlled by changing the ASF content and the thermal stability of composite hydrogels is enhanced with an increase in crystalline structure. The composite hydrogels showed similar lower critical solution temperatures (LCST) at about 32 °C, which matched well with the LCST of PNIPAAm. Finally, the obtained thermosensitive composite hydrogels exhibited enhanced mechanical properties, which can be tuned by varying the content of ASF. This strategy to prepare an ASF-based responsive composite hydrogel with enhanced mechanical properties represents a valuable route for developing the fields of ASF, and, furthermore, their attractive applications can meet the needs of different biomaterial fields.

ECM based injectable thermo-sensitive hydrogel on the recovery of injured cartilage induced by osteoarthritis

Intra-articular injection of anti-inflammatory drugs can be a promising strategy for recovery of injured articular cartilage. We prepared a series of injectable thermo-sensitive composite hydrogels, composed of Pluronic F127, glycosaminoglycan (GAG) and bone morphogenetic protein (BMP-2), which was designed to mimic extracellular matrix (ECM). The rheological properties and dissolution rate of composite hydrogels containing chondroitin sulfate or with different hyaluronic acid molecular mass (10k, 90k, 800k) were investigated. Meanwhile, bovine serum albumin (BSA) or FITC-BSA was chosen as model drug loaded into PF/GAG hydrogels to study their sustained release behavior in vitro. The results showed that hydrogels could maintain shapes for more than 16 days and the release rate of BSA in PF/GAG composite gels was much slower than in PF127 gels, due to the affinity between BSA and GAG. Furthermore, increasing the molecular weight of hyaluronic acid correspondingly increased hydrogel dissolution rate and BSA release in the hydrogels. Subsequently, MTT experiments were performed to investigate the toxicity of the hydrogels on mouse pre-osteoblast cell MC3T3-E1. In vivo anti-inflammation results showed that PF/GAG@BMP-2 composite hydrogels had the most efficient efficacy on recovery of injured cartilage, which is induced by osteoarthritis, compared to the control groups (PF127@BMP-2 or BMP-2 saline solution).

Rapid uniaxial actuation of layered bacterial cellulose/poly(N-isopropylacrylamide) composite hydrogel with high mechanical strength

This study deals with the unique morphology and properties of methylene diphenyl diisocyanate (MDI)-modified bacterial cellulose/poly(N-isopropylacrylamide) (BC/PNIPAAm) composite hydrogel prepared by in situ polymerization method. The influence of the molar ratio of MDI/glucose unit of BC on the properties of the resulting hydrogel was investigated. Scanning electron microscopic analysis revealed that after the MDI modification the BC/PNIPAAm hydrogel could preserve the unique layered (known as anisotropic) structure. The mechanical property evaluated by stress–strain test was significantly enhanced when compared to that of neat PNIPAAm hydrogel, due to the presence of the BC matrix as well as the MDI modification. Based on the deswelling behaviors, the BC/PNIPAAm hydrogel exhibited improved and controlled responsive rate when compared with neat PNIPAAm hydrogel. Furthermore, the anisotropic thermo-sensitive property was proved by temperature-responsive test with the fact that the composite hydrogel could only deswell and swell in the axial perpendicular to the layers. Along with desired recyclability, the present composite hydrogel may have an application as artificial muscles.

Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors.

Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy.

AMPHIPHILIC POLYMER-ASSISTED SYNTHESIS OF HYDROXYAPATITE PARTICLES AND THEIR INFLUENCE ON THE RHEOLOGICAL AND MECHANICAL PROPERTIES OF THERMOSENSITIVE HYDROGELS

Polymeric composite materials hold promise for versatile advanced applications. Of utmost importance for these applications is incorporating inorganic particles within polymer matrices which lead to multifunctional polymeric composites with desired functions. Specifically, thermosensitive polymeric hydrogels incorporating particle fillers have elicited widespread interest because of promising applications in drug delivery, tissue engineering, and medical devices. Although these materials are frequently discussed in many research fields, there are no decisive conclusions reported in literature, showing how the particle filler affects the rheological and mechanical behaviors of the resulting hydrogels. In this research, hydroxyapatite (HAp) bioceramics with definable morphologies were synthesized in order to reveal their effects on the resulting properties of HAp/polymer composite hydrogels. HAp particles with spherical, sheet-like and rod-like shapes were prepared with assistance by adding amphiphilic surfactant, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) in synthesis. Thermosensitive composite hydrogels with controllable rheological and mechanical properties were thus developed by incorporating HAp particles into poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA) hydrogel. Experimental results revealed that the rheological and mechanical properties of the resultant HAp/PEG-PLGA composite hydrogel not only influenced by the added HAp particle amount, but also by the particle morphology and interactions between particles and hydrogels. The findings from this research provide a critical guideline for designing thermosensitive composite hydrogels with required rheological and mechanical properties.

Effect of hydroxyapatite particles on the rheological behavior of poly(ethylene glycol)-poly(lactic-co-glycolic acid) thermosensitive hydrogels

Thermosensitive composite hydrogels incorporated with particles have been considered as next-generation biomaterials for numerous applications. However, experimental results reported in literature are not yet completely free of controversy with regard to how the particle filler affects the rheological behaviors of the resulting hydrogels. In this study, a simple method was developed to synthesize hydroxyapatite (HA) particles with definable morphology (rod and sheet) using hydrothermal process. The size of HA particles, ranging from 46 to 1149 nm, could be tailored by utilizing a sodium oleate surfactant. These HA particles introduced into thermosensitive hydrogels of poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) to systematically investigate the particle effect on the rheological behaviors of resulting HA-hydrogels. Experimental data confirm the mechanical and rheological behaviors of resulting HA-hydrogels were significantly influenced by particle morphology (size and shape) and the surfactant on the surface of the particle. These results act as solid evidences to highlight the crucial role of particles for developing composite hydrogels with desire thermosensitivity and mechanical properties for use in bioengineering applications.

Mechanical, rheological and release behaviors of a poloxamer 407/ poloxamer 188/carbopol 940 thermosensitive composite hydrogel.

The aims of this study were to prepare a thermosensitive composite hydrogel (TCH) by mixing 24% (w/v) poloxamer 407 (P407), 16% (w/v) poloxamer 188 (P188) and 0.1% (w/v) carbopol 940 (C940), and to determine the effect of natural borneol/ (2-hydroxypropyl)-β-cyclodextrin (NB/HP-β-CD) inclusion complex on the phase transition temperature, mechanical, rheological properties, and release behaviors of the TCH using the tube inversion method, a texture analyzer, a rheometer, and in vitro release , respectively. The results showed that as the concentration of NB/HP-β-CD increased, the phase transition temperature of the TCH was increased from 37.26 to 38.34 °C and the mechanical properties of the TCH showed that the hardness, cohesiveness, strength, and adhesiveness were increased from 0.025 to 0.064 kg, 0.022 to 0.064 kg, 0.110 to 0.307 kg and 0.036 to 0.105 kg, respectively, but the rheological properties of the TCH showed that G′, G′′ and η were decreased from 7,760 to 157.50 Pa, 1,274 to 36.28 Pa and 1,252 to 25.37 Pas, respectively. The in vitro release showed that an increasing NB/HP-β-CD concentration decreased the release rate of NB from the TCH, but the amount of NB released was more than 96% at 60 min, which showed the TCH had good release behavior.