Long-Term Implantability of Resorbable Carboxymethyl Cellulose/Chitosan Microspheres in a Rabbit Renal Arterial Embolization Model.

PURPOSE: To determine the physiologic response to resorbable carboxymethyl cellulose/chitosan (CMC/CN) microspheres in a long-term rabbit model, including the clinical response, gross pathology, and histopathology. MATERIALS AND METHODS: Six rabbits were embolized with CMC/CN microspheres (300-500 µm) in one kidney via an inferior renal artery branch. Angiography was performed immediately before and after embolization and prior to killing at 6 months (180 ± 7 days, n = 3) and 12 months (365 ± 10 days, n = 3). A complete necropsy was performed on each animal with dissection of the kidneys and harvesting of additional tissues as per ISO-10993-part 6 and ISO-10993-part 11 guidelines. All tissues were processed and stained for pathological analysis. RESULTS: The caudal third of target kidneys was successfully embolized with CMC/CN microspheres. Over the course of the study, there were neither notable clinical signs in either embolization group nor significant changes in the tissue/body weight ratio between 6- and 12-month time points. Gross examination revealed that all embolized kidneys had morphologic features consistent with infarction resulted from microsphere delivery. The percentage of infarction decreased from 9.1% ± 5.7% at 6 months to 1.9% ± 0.4% at 12 months. Microscopically, infarcted areas demonstrated evidence of chronic injury and repair, including loss of renal parenchyma with replacement fibrosis, tubular regeneration, and minimal to mild lymphoplasmacytic inflammation without any active changes such as necrosis or neutrophilic inflammation. CONCLUSION: No systemic toxicity was observed in the animals 6 and 12 months after CMC/CN microspheres delivery. The local tissue response was mild.

In vitro evaluation of sunitinib loaded bioresorbable microspheres for potential application in arterial chemoembolization.

Drug-loadable bioresorbable microspheres (BRMS) are designed for treating hypervascular tumors through chemoembolization, thereby reducing systemic side effects via controllable local delivery. The present study investigated the degradation and loading capability of bioresorbable microspheres with an anti-angiogenic agent, sunitinib, and then evaluated the release profiles in different media (PBS, 10µg/mL and 4mg/mL lysozyme solutions), and tested catheter deliverability as well as potential antiangiogenic effects of the loaded microspheres. The dry weight of the BRMS showed a consistent decrease over the period of incubation in a 10µg/mL lysozyme solution with 61.3% mass remaining on day 21. Sunitinib was loaded efficiently onto the microspheres, with smaller sizes exhibiting a slightly faster loading and release rate. At 2h, the loading percentages were 99.28%, 97.95%, and 94.39% for 100-300, 300-500, and 500-700µm microspheres, respectively. At 8h, the percentage of drug released were 78.4±5.8%, 71.7±0.3%, and 67.0±2.9% for 100-300, 300-500, and 500-700µm microspheres under static medium conditions, respectively. Under replacing-medium conditions, the presence of 10µg/mL lysozyme slightly delayed the drug release while 4mg/mL lysozyme significantly facilitated the drug release from the microspheres as compared with PBS solution. Confocal imaging revealed an even distribution of sunitinib throughout the microspheres. Drug loaded microspheres were delivered through microcatheters smoothly without any clogging. Sunitinib retained its efficacy at reducing the viability of human endothelial cells after elution from the microspheres. Thus, these bioresorbable microspheres are promising for arterial chemoembolization.

In vitro comparative study of drug loading and delivery properties of bioresorbable microspheres and LC bead.

Drug loadable bioresorbable microspheres (BRMS) are specially designed for the treatment of hypervascular tumors through arterial embolization. These microspheres consist of carboxymethyl chitosan crosslinked with carboxymethyl cellulose, and are available at different size ranges varying from 50 to 900 µm in diameter. Similar to commercially available non-resorbable drug eluting microspheres, LC Bead® microspheres (LCB), BRMS were capable of loading more than 99 % of doxorubicin, an anticancer drug, from the solution within 2 h with highly similar kinetics (difference factor f 1 = 0.36; similarity factor f 2 = 97.99). Doxorubicin loaded BRMS exhibited the highest elution rate in the 30 % ethanol aqueous solution saturated with potassium chloride, and the elution time depended on the ratio between the amount of loaded BRMS and the volume of elution media. After injection through microcatheters, BRMS have a higher recovery rate of the microsphere weight than LCB (90.96 vs. 79.63 %, P = 0.026). Although loaded BRMS eluted more drug into the injection medium than loaded LCB (8.63 vs. 3.80 %, P = 0.0015), there was no significant difference in the drug delivery rate between BRMS and LCB (83.88 vs. 86.65 %, P = 0.504). This study compares the loading capability as well as the drug delivery rate of BRMS and a commercial product under a condition simulating a transcatheter arterial chemoembolization procedure and demonstrates the potential of drug loaded BRMS for the treatment of hypervascular tumors such as hepatocellular carcinoma.

Intra-articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine.

OBJECTIVES: Knee osteoarthritis (OA) is a debilitating condition that may ultimately require total knee arthroplasty (TKA). Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI). The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment. METHODS: A literature search was executed using Medline, Cochrane, and Embase with keywords "knee osteoarthritis" and "injection." Specifically, 45 articles that discussed intra-articular knee injection using corticosteroids, hyaluronic acid, analgesics, local anesthetics, and newer products of regenerative medicine, such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSC), were analyzed. Of these, eleven were level 1, three were level 2, twelve were level 3, two were level 4, and seventeen were level 5 evidence. Papers included animal models. RESULTS: Local anesthetics have potential side effects and may only be effective for a few hours. Morphine and ketorolac may provide significant pain relief for 24 hours. Corticosteroids may give patients weeks to months of effective analgesia, but complications may occur, such as systemic hyperglycemia, septic arthritis, and joint degradation . Hyaluronic acid is a natural component of synovial fluid, but efficacy with respect to analgesia is controversial. Platelet-rich plasma formulations, autologous conditioned serum, autologous protein solution, and mesenchymal stem cell injections contain anti-inflammatory molecules and have been proposed to attenuate joint destruction or potentially remodel the joint. CONCLUSIONS: Currently, knee OA treatment does not address the progressively inflammatory environment of the joint. More investigation is needed regarding products of regenerative medicine, but they may ultimately have profound implications in the way knee OA is managed.

Calibrated Bioresorbable Microspheres as an Embolic Agent: An Experimental Study in a Rabbit Renal Model.

PURPOSE: To evaluate the time frame of resorption and tissue response of newly developed bioresorbable microspheres (BRMS) and vessel recanalization after renal embolization. MATERIALS AND METHODS: Embolization of lower poles of kidneys of 20 adult rabbits was performed with BRMS (300-500 µm). Two rabbits were sacrificed immediately after embolization (day 0). Three rabbits were sacrificed after follow-up angiography at 3, 7, 10, 14, 21, and 30 days. The pathologic changes in the renal parenchyma, BRMS degradation, and vessel recanalization were evaluated histologically and angiographically. RESULTS: Embolization procedures were successfully performed, and all animals survived without complication. Infarcts were observed in all kidneys that received embolization harvested after day 0. Moderate degradation of BRMS (score = 1.07 ± 0.06) was observed by day 3. Of BRMS, 95% were resorbed before day 10 with scant BRMS materials remaining in the arteries at later time points. Partial vessel recanalization was observed by angiography starting on day 3, whereas new capillary formation was first identified histologically on day 7. Vascular inflammation associated with BRMS consisted of acute, heterophilic infiltrate at earlier time points (day 3 to day 10); this was resolved with the resorption of BRMS. Inflammation and fibrosis within infarcted regions were consistent with progression of infarction. CONCLUSIONS: BRMS were bioresorbable in vivo, and most BRMS were resorbed before day 10 with a mild tissue reaction. Vessel recanalization occurred secondary to the resorption of BRMS.

Calibrated bioresorbable microspheres: a preliminary study on the level of occlusion and arterial distribution in a rabbit kidney model.

PURPOSE: To assess the level of occlusion and arterial distribution of calibrated bioresorbable microspheres (BRMS-I and BRMS-II) compared with tris-acryl gelatin microspheres (TGMS) after renal embolization. MATERIALS AND METHODS: Six rabbits underwent renal embolization with 100-300 µm BRMS-I and TGMS; three rabbits received partial occlusion (group 1, n = 3), and three rabbits received total occlusion (group 2, n = 3). Four other rabbits received 100-300 µm BRMS-II (with higher cross-linking density than BRMS-I) in the left kidneys reaching total occlusion (group 3, n = 4). Coronal sections of the kidneys were histologically analyzed. Ease of injection, microsphere deformation, vessel sizes, and arterial distribution were assessed. RESULTS: The injection of BRMS-I, BRMS-II, and TGMS through microcatheters went smoothly without any clogging. In group 1, BRMS identification was easier than TGMS. In group 2, both BRMS-I and TGMS were observed in all three arterial levels (interlobar, arcuate, and interlobular arteries) without a significant difference (P = .84). BRMS-I were not significantly different from TGMS in the mean diameter of vessels occluded (197 µm ± 23 vs 158 µm ± 21, P = .25) or the microsphere deformation (8.85% ± 0.53% vs 11.80% ± 0.64%, P = .071). In group 3, the arterial distribution of BRMS-II was significantly different from BRMS-I and TGMS (P < .0001). CONCLUSIONS: In occluding arteries, 100-300 µm BRMS-I were not significantly different from 100-300 µm TGMS. Arterial distribution of BRMS can be influenced by their cross-linking density.

An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies.

We present here the characteristics of an in situ forming hydrogel prepared from carboxymethyl chitosan and oxidized carboxymethyl cellulose for interventional therapies. Gelation, owing to the formation of Schiff bases, occurred both with and without the presence of a radiographic contrast agent. The hydrogel exhibited a highly porous internal structure (pore diameter 17±4 µm), no cytotoxicity to human umbilical vein endothelial cells, hemocompatibility with human blood, and degradability in lysozyme solutions. Drug release from hydrogels loaded with a sclerosant, tetracycline, was measured at pH 7.4, 6 and 2 at 37°C. The results showed that tetracycline was more stable under acidic conditions, with a lower release rate observed at pH 6. An anticancer drug, doxorubicin, was loaded into the hydrogel and a cumulative release of 30% was observed over 78 h in phosphate-buffered saline at 37°C. Injection of the hydrogel precursor through a 5-F catheter into a fusiform aneurysm model was feasible, leading to complete filling of the aneurysmal sac, which was visualized by fluoroscopy. The levels of occlusion by hydrogel precursors (1.8% and 2.1%) and calibrated microspheres (100-300 µm) in a rabbit renal model were compared. Embolization with hydrogel precursors was performed without clogging and the hydrogel achieved effective occlusion in more distal arteries than calibrated microspheres. In conclusion, this hydrogel possesses promising characteristics potentially beneficial for a wide range of vascular intervention procedures that involve embolization and drug delivery.

In vitro and in vivo evaluation of biodegradable embolic microspheres with tunable anticancer drug release.

Natural polymer-derived materials have attracted increasing interest in the biomedical field. Polysaccharides have obvious advantages over other polymers employed for biomedical applications due to their exceptional biocompatibility and biodegradability. None of the spherical embolic agents used clinically is biodegradable. In the current study, microspheres prepared from chitosan and carboxymethyl cellulose (CMC) were investigated as a biodegradable embolic agent for arterial embolization applications. Aside from the enzymatic degradability of chitosan units, the cross-linking bonds in the matrix, Schiff bases, are susceptible to hydrolytic cleavage in aqueous conditions, which would overcome the possible shortage of enzymes inside the arteries. The size distribution, morphology, water retention capacity and degradability of the microspheres were found to be affected by the modification degree of CMC. An anticancer drug, doxorubicin, was successfully incorporated into these microspheres for local release and thus for killing cancerous cells. These microspheres demonstrated controllable degradation time, variable swelling and tunable drug release profiles. Co-culture with human umbilical vein endothelial cells revealed non-cytotoxic nature of these microspheres compared to monolayer control (P>0.95). In addition, a preliminary study on the in vivo degradation of the microspheres (100-300µm) was performed in a rabbit renal embolization model, which demonstrated that the microspheres were compatible with microcatheters for delivery, capable of occluding the arteries, and biodegradable inside arteries. These microspheres with biodegradability would be promising for embolization therapies.

Bioresorbable hydrogel microspheres for transcatheter embolization: preparation and in vitro evaluation.

PURPOSE: To develop and evaluate a bioresorbable spherical material for embolization. MATERIALS AND METHODS: New bioresorbable hydrogel microspheres were prepared from carboxymethyl cellulose and chitosan by using an inverse emulsion method. Size distribution of the microspheres was determined with a microscope, and the colorability was tested with Evans blue dye. The compressibility was examined with a texture analyzer. After sieving, the suspendability of the microspheres was tested in saline solution/contrast agent mixture in different ratios, and then the injectability was tested with microcatheters (lumen sizes of 0.0165, 0.019, and 0.027 inches). The in vitro degradability tests were performed in a lysozyme solution. Cell culture study of the microspheres was performed with human fibroblasts. RESULTS: The microspheres exhibit diameters of 100-1,550 µm with a transparent appearance. Their fracture force can reach 0.58-0.88 N, and fracture deformation varies from approximately 70% to 95% of their original size. These microspheres can be colored by Evans blue dye, and uniform subgroups of microspheres can be readily obtained by sieving. Within 3 minutes, the microspheres form a stable suspension in a 4:6 contrast agent/saline solution mixture, which can be easily injected through microcatheters without aggregating or clogging. These microspheres are biodegradable, with degradation times varying from 2 weeks to 1 month, depending on their composition. Cell culture studies reveal no adverse effect on the growth of human fibroblasts in the presence of the microspheres. CONCLUSIONS: A biodegradable and noncytotoxic microsphere was successfully prepared. It can be well suspended in the contrast solution and easily injected through a microcatheter.

Doxorubicin loading and eluting characteristics of bioresorbable hydrogel microspheres: in vitro study.

Non-bioresorbable drug eluting microspheres are being increasingly used for the treatment of unresectable liver tumors, whereas bioresorbable microspheres have not received much attention. In this study, bioresorbable microspheres prepared from chitosan and carboxymethyl cellulose were loaded with doxorubicin (Doxo) via ion-exchange interactions with carboxylic groups in the microspheres. With a 25-40% decrease in the microsphere size depending on their size ranges, the microspheres could load a maximum of 0.3-0.7 mg Doxo/mg dry spheres. As confirmed by confocal microscopy, Doxo was mainly concentrated in the outer 20±5 µm surface layer of the microspheres. The loaded microspheres were stable in aqueous dispersions without aggregation for a prolonged period of time but degradable in a lysozyme solution. Furthermore, the loaded microspheres exhibited a noticeable pH-sensitive behavior with accelerated release of Doxo in acidic environment due to the protonation of carboxylic groups in the microspheres. Compared to commercial non-resorbable drug eluting beads, the loaded bioresorbable microspheres showed a sustained release manner in phosphate buffered saline (PBS). The release data were fitted to an empirical relationship, which reveals a non-Fickian transport mechanism (n=0.55-0.59). These results demonstrate that the bioresorbable microspheres are promising as attractive carriers for Doxo.

Novel macromolecular crosslinking hydrogel to reduce intra-abdominal adhesions.

BACKGROUND: The aim of this study was to compare the anti-adhesion efficacy of a biodegradable, in situ, macromolecular cross-linking hydrogel made from oxidized dextran/N-carboxyethyl chitosan (Odex/CEC) with a commercially available carboxymethylcellulose/modified hyaluronan barrier film (Seprafilm; Genzyme Corporation, Cambridge, MA) in a rat cecum abrasion model. METHODS: The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The 2% Odex/CEC hydrogel treatment was applied by syringe to coat both the cecal and the abdominal wall insults, while other animals were treated with Seprafilm applied to the cecal injury only. Control animals did not receive any treatment. Animals were sacrificed after post operative day 21 and adhesion severity was quantitatively graded using a whole number scale from 0 - 3. Histological analysis was also performed for animals receiving Odex/CEC hydrogel treatment and no treatment (control). RESULTS: Mean adhesion score was 2.09+/-1.22 for control animals, 1.00+/-1.00 for 2% Odex/CEC hydrogel animals, and 1.25+/-1.22 for Seprafilm animals. Hydrogel treated animals showed significantly lower adhesion scores than control animals (P<0.05), while Seprafilm demonstrated a marginally lower adhesion score (P<0.1) compared with the controls. Histological analysis of an Odex/CEC treated rat showed tissue repair and small fragments of hydrogel inside both healed abdominal and cecal surfaces. CONCLUSIONS: Both Seprafilm and the 2% Odex/CEC hydrogel showed a significantly decreased adhesion score compared with the control. However, the hydrogel, compared with Seprafilm, offers ease of application and ability to conform to complex tissue geometries that could provide surgeons with another prophylactic treatment to prevent abdominal adhesions.

In vitro and in vivo suppression of cellular activity by guanidinoethyl disulfide released from hydrogel microspheres composed of partially oxidized hyaluronan and gelatin.

This paper describes the preparation of oxidized hyaluronan crosslinked gelatin microspheres for drug delivery. Microspheres were prepared by a modified water-in-oil-emulsion crosslinking method, where three-dimensional crosslinked hydrogel microspheres formed in the absence of any extraneous crosslinker. SEM analyses of the microspheres showed rough surfaces in their dried state with an average diameter of 90 microm. Lyophilization of fully swollen microspheres revealed a highly porous structure. Guanidinoethyl disulfide (GED) was used as a model drug for incorporation into the microspheres; encapsulation of GED was confirmed by HPLC. There was an inverse correlation between the diameters of the microspheres with their GED loading. Macrophage was used as a model cell to evaluate the in vitro efficacy of GED release from the microspheres. The in vivo efficacy of the microspheres was further validated in a mouse full-thickness transcutaneous dermal wound model through suppression of cell infiltration.

Non-cytotoxic, in situ gelable hydrogels composed of N-carboxyethyl chitosan and oxidized dextran.

A series of in situ gelable hydrogels were prepared from oxidized dextran (Odex) and N-carboxyethyl chitosan (CEC) without any extraneous crosslinking agent. The gelation readily took place at physiological pH and body temperature. The gelation process was monitored rheologically, and the effect of the oxidation degree of dextran on the gelation process was investigated. The higher the oxidation degree of Odex, the faster the gelation. A highly porous hydrogel structure was revealed under scanning electron microscopy (SEM). Swelling and degradation of the Odex/CEC hydrogels in PBS showed that both swelling and degradation were related to the crosslinking density of the hydrogels. In particular, the hydrogels underwent fast mass loss in the first 2 weeks, followed by a more moderate degradation. The results of long-term cell viability tests revealed that the hydrogels were non-cytotoxic. Mouse fibroblasts were encapsulated in the hydrogels and cell viability was at least 95% within 3 days following encapsulation. Furthermore, cells entrapped inside the hydrogel assumed round shape initially but they gradually adapted to the new environment and spread-out to assume more spiny shapes. Additionally, the results from applying the Odex/CEC system to mice full-thickness transcutaneous wound models suggested that it was capable of enhancing wound healing.

Mechanically strong double network photocrosslinked hydrogels from N,N-dimethylacrylamide and glycidyl methacrylated hyaluronan.

Hyaluronan (HA) is a natural polysaccharide abundant in biological tissues and it can be modified to prepare biomaterials. In this work, HA modified with glycidyl methacrylate was photocrosslinked to form the first network (PHA), and then a series of highly porous PHA/N,N-dimethylacrylamide (DAAm) hydrogels (PHA/DAAm) with high mechanical strength were obtained by incorporating a second network of photocrosslinked DAAm into PHA network. Due to the synergistic effect produced by double network (DN) structure, despite containing 90% of water, the resulting PHA/DAAm hydrogel showed a compressive modulus and a fracture stress over 0.5 MPa and 5.2 MPa, respectively. Compared to the photocrosslinked hyaluronan single network hydrogel, which is generally very brittle and fractures easily, the PHA/DAAm hydrogels are ductile. Mouse dermal fibroblast was used as a model cell line to validate in vitro non-cytotoxicity of the PHA/DAAm hydrogels. Cells deposited extracellular matrix on the surface of these hydrogels and this was confirmed by positive staining of Type I collagen by Sirius Red. The PHA/DAAm hydrogels were also resistant to biodegradation and largely retained their excellent mechanical properties even after 2 months of co-culturing with fibroblasts.

Self-crosslinkable hydrogels composed of partially oxidized hyaluronan and gelatin: in vitro and in vivo responses.

Self-crosslinkable hydrogels had been formulated from two precursors, partially oxidized hyaluronan (oHA) and gelatin. The physicochemical properties of the resulting hydrogels have been elucidated by instrumental analyses (FTIR, SEM, and rheometry). These hydrogels were highly porous with an average pore size of 60 microm, and evidently, accommodative to cell infiltration. Increasing the oxidation degree of oHA resulted in corresponding increases in hydrogels' storage moduli and decreases in water uptake. Dermal fibroblasts were used to study the cell-hydrogel interactions in vitro. Both the hydrogels and their degradation byproducts are biocompatible as indicated by long-term cell viability assay. In addition, significant amount of cells migrated into the hydrogels and they aligned into highly organized arrays. When cultured with cells, the hydrogels underwent degradation within 4 weeks depending on composition with obvious loss of cohesiveness over time. The good biocompatibility and biodegradability of oHA/gelatin hydrogel were further demonstrated in mice subdermal implantations. Lastly, in vitro and in vivo depositions of extracellular matrix in hydrogels by cells were demonstrated by SEM analyses.

Material properties in unconfined compression of human nucleus pulposus, injectable hyaluronic acid-based hydrogels and tissue engineering scaffolds.

Surgical treatment for lower back pain related to degenerative disc disease commonly includes discectomy and spinal fusion. While surgical intervention may provide short-term pain relief, it results in altered biomechanics of the spine and may lead to further degenerative changes in adjacent segments. One non-fusion technique currently being investigated is nucleus pulposus (NP) support via either an injectable hydrogel or tissue engineered construct. A major challenge for either approach is to mimic the mechanical properties of native NP. Here we adopt an unconfined compression testing configuration to assess toe-region and linear-region modulus and Poisson's ratio, key functional parameters for NP replacement. Human NP, experimental biocompatible hydrogel formulations composed of hyaluronic acid (HA), PEG-g-chitosan, and gelatin, and conventional alginate and agarose gels were investigated as injectable NP replacements or tissue engineering scaffolds. Testing consisted of a stress-relaxation experiment of 5% strain increments followed by 5-min relaxation periods to a total of 25% strain. Human NP had an average linear-region modulus of 5.39 +/- 2.56 kPa and a Poisson's ratio of 0.62 +/- 0.15. The modulus and Poisson's ratio are important parameters for evaluating the design of implant materials and scaffolds. The synthetic HA-based hydrogels approximated NP well and may serve as suitable NP implant materials.

Rheological characterization of in situ crosslinkable hydrogels formulated from oxidized dextran and N-carboxyethyl chitosan.

The gelation kinetics of an in situ gelable hydrogel formulated from oxidized dextran (Odex) and N-carboxyethyl chitosan (CEC) was investigated rheologically. Both Schiff base mediated chemical and physical crosslinking account for its rapid gelation (30-600 s) between 5 and 37 degrees C. The correlation between gelation kinetics and hydrogel properties with Odex/CEC concentration, their feed ratio, and temperature were elucidated. The gelation time determined from crossing over of storage moduli (G') and loss moduli (G' ') was in good agreement with that deduced from frequency sweeping tests according to the Winter-Chambon power law. The power law exponents for a 2% (w/v) Odex/CEC solution (ratio 5:5) at the gel point was 0.61, which is in excellent agreement with the value predicted from percolation theory (2/3). Temperature dependence of gelation time for the same hydrogel formulation is well-described by an Arrhenius plot with its apparent activation energy calculated at 51.9 kJ/mol.

Long-range self-governing motion of polymer gel on a gradiently charged insulating substrate.

Herein, we report a special poly(vinyl alcohol)/dimethylsulfoxide (PVA/DMSO) gel electromechanical system with great self-governed capability. The system is operated in air by applying a noncontacted DC electric field. When the applied electric field exceeds a certain critical value, the gel exhibits fast and self-governing locomotion on the gradiently charged glass substrate. In contrast to field-controlled gel systems developed earlier, the crawling direction of the gel is independent of the direction of the applied electric field and can be actively controlled. The maximum crawling velocity can reach 3.22 mm s(-1), which is much larger than that of the actuators described earlier. Furthermore, some factors that influence the critical driving electric field and the average crawling speed of the gel were studied. The mechanism analysis indicates that, the self-governing linear motion of the gel is due to the spatially and temporally varying electrostatic interaction between the gel and the applied electric field in response to the gradient change of the charge density and the charge polarity on the substrate.

Biologically inspired path-controlled linear locomotion of polymer gel in air.

A novel approach based on electrohydrodynamic behavior of a dielectric liquid pattern in electric field was developed to fabricate a poly(vinyl alcohol)/dimethyl sulfoxide (PVA/DMSO) gel electromechanical system. Driving experiments indicate that this system could be well-operated in air by using a direct current (DC) electric field, and the gel exhibits a long-range path-controlled snaillike or snakelike motion with a fast crawling speed of 14.4 mm/s. Some factors, such as the applied electric field and the mass of the gel on the average crawling speed of the gel at linear path and curvilinear path, are investigated. Furthermore, a transition between snaillike gaits and snakelike gaits of the gel is also further studied in this system. The mechanism analysis suggests that this path-controlled motion of the gel arises from the drag of the spatial varied shear force F originated from the electrohydrodynamic flow of the solvent in and out of the gel.