Preparation and characterization of novel cationic copolymer hydrogels with pH sensitivity and thermosensitivity

Cationic hydrogels were synthesized through the copolymerization of N‐isopropylacrylamide and dimethylaminoethylmethacrylate. N,N′‐Methylenebisacrylamide was used as a crosslinking agent, and sodium bisulfite/ammonium persulfate was used as an initiator. The equilibrium and dynamic swelling properties were investigated to reveal the pH sensitivity and thermosensitivity of the hydrogels. The conclusion was drawn that the prepared cationic hydrogels demonstrated critical sensitivity at 37°C and pH 7.0–8.0 and that the stronger the acidity was of the buffered solution, the shorter the equilibrium swelling time was of the hydrogels. Drug‐release experiments in vitro were carried out at 37°C (close to body temperature), at pH 1.4 (close to the pH of the stomach), and at pH 7.4 (close to the pH of the intestine). The release results indicated that the drug (chloramphenicol) was released more rapidly from the prepared hydrogel in a pH 1.4 buffered solution than in a pH 7.4 one, and this was consistent with the results predicted from the experiments of the swelling kinetics. Moreover, the drug‐release process was confirmed by scanning electron micrographs of the hydrogels embedded with chloramphenicol. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 3602–3608, 2006     

Preparation and Swelling Study of a pH-Dependent Interpolymeric Hydrogel Based on Chitosan for Controlled Drug Release

Novel pH-dependent, biodegradable interpolymeric network (IPN) hydrogels were prepared for controlled drug release investigations. The IPN hydrogels were prepared by irradiation of solutions of N-acryloyglycine (NAGly), polyethylene glycol diacrylate (PEGDA) mixed with chitosan, in the presence of a lower amount of glutaraldehyde as the crosslinker and using 2,2-dimethoxy-2-phenyl acetophenone as the photo-initiator. The equilibrium swelling studies were carried out for the gels at 37°C in buffer solutions of pH 2.1 and 7.4 (simulated gastric and intestinal fluids, respectively). 5-Fluorouracil (5-FU) was entrapped, as a model therapeutic agent, in the hydrogels and equilibrium-swelling studies were carried out for the drug-entrapped gels at 37°C. The in-vitro release profiles of the drug were established at 37°C in pH 2.1 and 7.4.     

Synthesis and characterization of 2‐hydroxyethylmethacrylate/2‐(3‐indol‐yl)ethylmethacrylamide‐based novel hydrogels as drug carrier with in vitro antibacterial properties

In this study, a new cationic monomer 2‐(3‐indol‐yl)ethylmethacrylamide (IEMA) derived from tryptamine was synthesized in a single step and characterized by Fourier transform infrared (FTIR), ¹H‐NMR, and ¹³C‐NMR. Then, one‐step preparation of novel poly[2‐hydroxyethylmethacrylate‐c‐2‐(3‐indol‐yl)ethylmethacrylamide], or p(HEMA‐c‐IEMA), copolymeric hydrogels has been performed successfully with IEMA and 2‐hydroxyethylmethacrylate (HEMA) as monomers using free radical aqueous polymerization. The hydrogels were characterized with scanning electron microscopy, FTIR, elemental analysis, thermogravimetric analysis, and texture profile analysis instruments. p(HEMA‐c‐IEMA) hydrogels were used for swelling, diffusion, drug release, and antibacterial activity studies. The drug‐release behavior of the hydrogels was determined as a function of time at 37 °C in pH 1.2 and 7.2. The swelling and drug‐release studies showed that an increased IEMA amount caused a higher increase in swelling and drug‐release values. Additionally, zero‐order, first‐order, and Higuchi equation kinetic models were applied to the drug‐release data, and the data fit well in the Higuchi model, and the Peppas power‐law model was applied to the release mechanism. Finally, the antibacterial activities of the hydrogels were screened against Gram‐positive bacteria (Bacillus cereus and Staphylococcus aureus) and Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium). © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45550.     

Poly(vinyl alcohol)/chitosan/honey/clay responsive nanocomposite hydrogel wound dressing

Many efforts have been made to develop modern wound dressings to overcome limitations of traditional ones. Smart nanocomposite hydrogels are appropriate candidates. In this work, a novel responsive nanocomposite hydrogel based on poly(vinyl alcohol)/chitosan/honey/clay was developed and evaluated as a novel wound dressing. The morphology and properties of synthesized nanocomposite hydrogels loaded with honey as a drug model were investigated. The exfoliated morphology of nanocomposite was confirmed by X‐ray diffractometry. Swelling studies were performed at 20 and 37 °C at various pH. The results showed that swelling increased as a result of temperature rise and maximum swelling occurred at a pH of 2. In vitro release of honey was also studied at the same conditions. Corresponding results indicated faster honey release rate at higher pH values. MTT results exhibited no cytotoxicity in nanocomposite hydrogel system. Investigation of antibacterial activity revealed more than 99% antibacterial activity for proposed system. In vivo results confirmed the wound healing ability of developed system. Generally, appropriate properties of proposed system made it ideal in wound dressing applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46311.     

Swelling characteristics and in vitro drug release study with pH‐ and thermally sensitive hydrogels based on modified chitosan

The grafting of a poly(ethylene glycol) diacrylate macromer onto a chitosan backbone was carried out with different macromer concentrations. The grafting was achieved by (NH₄)₂Ce(NO₃)₆‐induced free‐radical poly merization. Biodegradable, pH‐ and thermally responsive hydrogels of poly(ethylene glycol)‐g‐chitosan crosslinked with a lower amount of glutaraldehyde were prepared for controlled drug release studies. Both the graft copolymers and the hydrogels were characterized with Fourier transform infrared, elemental analysis, and scanning electron microscopy. The obtained hydrogels were subjected to equilibrium swelling studies at different temperatures (25, 37, and 45°C) in buffer solutions of pHs 2.1 and 7.4 (similar to those of gastric and intestinal fluids, respectively). 5‐Fluorouracil was entrapped in these hydrogels, and equilibrium swelling studies were carried out for the drug‐entrapped gels at pHs 2.1 and 7.4 and 37°C. The in vitro release profile of the drug was established at 37°C and pHs 2.1 and 7.4. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 977–985, 2006     

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     

Design,Synthesis, Characterization,Swelling and in Vitro Drug Release Behavior of Composite Hydrogel Beads Based on Methotrexate and Chitosan Incorporating Antipyrine Moiety

Novel biodégradable pH and thermal-responsive hydrogels were prepared for controlled drug delivery studies via reaction of chitosan with 4-chloroacetylantipyrine in DMF/H₂O, followed by heating of the formed poly [acetylantipyrine-chitosan] with glutaraldehyde as a crosslinking agent to give the hydrogels. These hydrogels were subjected to equilibrium swelling studies at different temperatures (25°C, 37°C and 45°C) in solutions of pH 2.1 and 7.4. Methotrexate (MTX) was entrapped in the hydrogels, and drug release studies were carried out at 37 °C in solutions at pH 2.1 and 7.4.     

Effect of Pluronic F127 on the 3D pore morphology of poly(N-isopropylacrylamide-co-acrylic acid) hydrogels and their nitric oxide release from S-nitrosoglutathione

Changing the pore morphology of hydrogels can be an effective strategy to modulate their drug release profiles. Herein, Pluronic F127 was used to change the three-dimensional pore morphology of crosslinked poly(N-isopropylacrylamide-co-acrylic acid) (P[NIPAm-co-AAc]) hydrogels. F127 reduced the pore diameters from 20 ± 4 to 2.9 ± 0.4 μm and from 11 ± 1 to 1.4 ± 0.4 μm in hydrogels synthesized at 8 and 30°C, respectively. Small-angle X-ray scattering indicates that the segregation of the F127 during the polymerization process induces F127 phase transitions from unimers (at 8°C) or cubic-packed micelles (at 30°C) to a lamellar structure. P(NIPAm-co-AAc) hydrogels charged with S-nitrosoglutathione (GSNO), released nitric oxide (NO) spontaneously during hydration. The decrease in the pore diameter led to a twofold to threefold increase in the rate of water absorption and a fourfold to sixfold increase in the rate of NO release of the hydrogels. F127 can be used to change the pore morphology of P(NIPAm-co-AAc) hydrogels, with concomitant changes in their rate of hydration and NO release from GSNO, opening a new perspective for their use in topical NO delivery.     

Application of syndiotacticity‐rich PVA hydrogels prepared at a low temperature to thermo‐ and pH‐responsive release devices

Three kinds of physically cross‐linked syndiotacticity‐rich poly(vinyl alcohol) (s‐PVA) hydrogels were prepared at 0°C with use of the buffer solutions (BS) of pHs 4.0, 7.4, and 9.0. Three gels swelled at first and then began to shrink after 12 h when they were dipped in the same BS for preparation at higher temperature than 0°C. The release of Brilliant Blue (3 mg/1 mL) from the cylindrical gels prepared using BS of pH 7.4 was studied at 27, 37, and 47°C. Brilliant Blue has been released spending 4–12 h almost completely. The rate of release from the gel at temperatures of 27, 37, and 47°C became large with increasing temperature. The main factor on release of Brilliant Blue is not the contraction of gel, but swelling, because the degree of swelling (DS) became large with increasing temperatures for 27, 37, and 47°C. The rate of release from the gel (pH 4.0) was larger than that (pH 7.4) due to the increased DS of the hydrogel in early step at pH of 4.0. The apparent diffusion exponents of these releases at pH 7.4 evaluated from first 60% of the fractional release were lower than 0.45 due to the swelling during release. The exponent at pH 4.0 was 0.45 due to immediate swelling. The on‐off of shrinking behavior of atactic PVA (a‐PVA) hydrogel was observed under several temperature changes. The rate of release of Brilliant Blue at 5°C was lower than that at 27°C and no change was observed at 5°C after one on‐off cycle. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 41–46, 2000     

Poly(N-isopropylacrylamide)/mesoporous silica thermosensitive composite hydrogels for drug loading and release

Temperature-sensitive hydrogels are attracting increasing attention for controlled drug delivery. However, achieving high drug loadings and sustained drug release remains challenging. Herein, we describe the successful synthesis of a series of novel temperature-sensitive poly(N-isopropylacrylamide) (PNIPA)/mesoporous silica nanoparticles (MSN) hydrogels by physical crosslinking of NIPA with MSN. The external and internal structures, temperature sensitivity, drug-loading capacity, and blood compatibility of the PNIPA/MSN composite hydrogels are studied. Results show that MSN addition improved the network structure and adjusted the size of the hole, MSN could also act as drug carrier, thereby enhancing the drug loading capacity. The composite hydrogels underwent a phase transition at 33.7 °C (at the lower critical solution temperature). The hemolysis rate of the composite hydrogels was less than 1%, thus they can be classified as a nonhemolytic materials with good biocompatibility. The composite hydrogels reported here thus have great potential in drug transport and temperature-activated drug release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48391.     

pH- and thermo-sensitive semi-IPN hydrogels composed of chitosan, <Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide,and poly(ethylene glycol)-<Emphasis Type="Italic">co</Emphasis>-poly(ε-caprolactone) macromer for drug delivery

In this study, semi-IPN chitosan/poly(N-isopropylacrylamide) (PNIPAAm) hydrogels have been prepared via in situ UV-photo-crosslinking of N-isopropylacrylamide monomer using poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-co-PCL) macromer as a crosslinker in the presence of chitosan. Swelling properties of the resultant hydrogels were studied by investigating pH- and temperature dependence of equilibrium swelling ratio and oscillatory swelling–deswelling kinetics. It was found that semi-IPN hydrogels responded to both temperature and pH changes, and such stimuli-responsiveness was rapidly reversible. The rheological measurements demonstrated that the incorporation of chitosan greatly improved the mechanical strength of the hydrogels prepared. The release profiles of bovine serum albumin (BSA) from the hydrogels were also evaluated. The results showed that the release rate of BSA was higher in pH 2.0 buffer solution than in pH 7.4 buffer solution at 37 °C. Such double-sensitive hydrogels have the potential to use as smart carriers for drug delivery systems.     

Release of tritium-labeled estradiol steroids from fully swollen hydrogels of polyurethane networks

Diffusion of uniformly dispersed tritium-labeled estradiol in water-swollen poly(ethylene oxide) -based hydrogels was studied by assaying the release of solute from cylindrical hydrogels into a finite volume of solution at 37°C. Fractional release followed a t^0.5 relationship for a range of radil between 0.20 and 0.35 cm and different polymer compositions with equilibrium water uptake of 220–750 parts per hundred dry polymer. Values of the diffusion coefficient were calculated from the fully swollen hydrogels, which represents the swelling and release profile quite accurately. © 1994 John Wiley & Sons, Inc.     

Synthesis and characterization of poly{N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid} hydrogels for drug delivery

A novel pH‐sensitive hydrogel system composed of itaconic acid (IA) and N‐[3‐(dimethylamino) propyl] methacrylamide was designed. This system was prepared by aqueous copolymerization with N,N‐methylene bisacrylamide as a chemical crosslinker. The chemical structure of the hydrogels was characterized by Fourier transform infrared (FTIR) spectroscopy. The microstructure and morphology of the hydrogels were evaluated by X‐ray diffraction (XRD) and scanning electron microscopy (SEM). The SEM study of hydrogels on higher magnification revealed a highly porous morphology with uniformly arranged pores ranging from 40 to 200 μm in size. XRD analysis revealed the amorphous nature of the hydrogels, and it was found that an increase in the IA content in the monomer feed greatly reduced the crystallinity of the hydrogels. Swelling experiments were carried out in buffer solutions at different pH values (1.2–10) at 37°C ± 1°C to investigate their pH‐dependent swelling behavior and dimensional stability. An increase in the acid part (IA) increased the swelling ratio of the hydrogels. Temperature‐sensitive swelling of the hydrogels was investigated at 20–70°C in simulated intestinal fluid. The hydrogels swelled at higher temperatures and shrank at lower temperatures. 5‐Aminosalicylic acid (5‐ASA) was selected as a model drug, and release experiments were carried out under simulated intestinal and gastric conditions. 5‐ASA release from the poly N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid‐80 (PDMAPMAIA‐80) hydrogel was found to follow non‐Fickian diffusion mechanism under gastric conditions, and a super case II transport mechanism was found under intestinal conditions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Properties of hydrogels of atactic poly(vinyl alcohol)/NaCl/H2O system and their application to drug release

In order to prepare cost‐effective physically cross‐linked hydrogels including food salt sodium chloride, samples, were prepared with various concentrations of NaCl and respective atactic poly(vinyl alcohol) (a‐PVA), and were evaluated. It had been observed that hydrogels containing NaCl concentration (9–11 wt%) along with a‐PVA concentration 9–5% respectively exhibited higher melting points (91.5–95.1 °C). A higher melting point characterizes the hydrogel composition of a system like a‐PVA(7%)/NaCl(11%)/H₂O. The swelling degree of this hydrogel was found to be comparatively better at 37 °C than at any other temperature studied here. However, irregular Fickian swelling was found at this temperature. The UV light absorption maximum at 362–364 nm and minimum at 351 nm for this hydrogel had been found as evidence of physical cross‐linking. A drug, theophylline was loaded by solvent‐sorption and feed‐mixture dissolving methods. The feed‐mixture dissolving method is better than solvent sorption because of high drug loading, comparatively low fraction release rate and more sustained‐release of drug than that of solvent‐sorption. Theophylline was released twice as fast from the hydrogel after solvent‐sorption drug loading (3 h) than from that which used the feed‐mixture dissolving method (6.5 h). Theophylline‐loaded hydrogels of this system (feed‐mixture dissolving) were then prepared at high temperature (60 °C) thawing for 6 h followed by chilling at 0.4 °C for 3 h as one cycle. And the drug release behaviour and mass transfer were found almost the same as for chilling (24 h at 0.4 °C)–thawing (48 h at room temperature). Drug release behaviour was studied as apparently irregular Fickian diffusion (Higuchi Matrix Dissolution Model). © 2002 Society of Chemical Industry     

Preparation and property of starch nanoparticles reinforced aldehyde–hydrazide covalently crosslinked PNIPAM hydrogels

Injectable, de‐crosslinkable, and thermosensitive hydrogels are obtained by hydrazide‐functionalized poly(N‐isopropylacrylamide) and aldehyde‐functionalized dextrin through in situ crosslinked method. Natural based and degradable starch nanoparticles (SNPs) are used as fillers in order to improve mechanical property of hydrogels. Internal morphology, dynamic modulus, thermosensitivity property, de‐crosslinking performance, drug release, and in vitro cytotoxicity of hydrogels are investigated. Results show that SNPs disperse well throughout hydrogel and have no significant influence on gelation time and de‐crosslinking performance. Elasticity property of composite hydrogel prepared from 9.0 wt % precursors with 1.5 wt % fillers is improved significantly by SNPs and maximum storage modulus reaches 399.2 kPa, but 89.6 kPa of unreinforced hydrogels. Hydrogels exhibit good thermosensitive performance at alternating cyclic temperature of 25 and 37 °C. Doxorubicin hydrochloride‐loaded hydrogels can release more than 25 days. No significant cytotoxicity to L929 fibroblast cells is observed through a CCK‐8 assay for hydrogels, precursors, and SNPs. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45761.     

Chitosan‐based interpolymeric pH‐responsive hydrogels for in vitro drug release

Two series of pH‐responsive biodegradable interpolymeric (IPN) hydrogels based on chitosan (Ch) and poly(vinyl alcohol) (PVA) were prepared for controlled drug release investigations. The first series was chemically crosslinked with different concentrations of glutaraldehyde and the second was crosslinked upon γ‐irradiation by different doses. The equilibrium swelling characteristics were investigated for the gels at 37°C in buffer solutions of pH 2.1 and 7.4 as simulated gastric and intestinal fluids, respectively. 5‐Fluorouracil (FU) was entrapped in the hydrogels, as a model therapeutic agent, and the in vitro release profiles of the drug were established at 37°C in pH 2.1 and 7.4. FTIR, SEM, and X‐ray diffraction analyses were used to characterize and investigate the structural changes of the gels with the variation of the blend composition and crosslinker content before and after the drug loading. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2864–2874, 2007     

Fluconazole release through semi‐interpenetrating polymer network hydrogels based on chitosan,acrylic acid,and citraconic acid

Semi‐interpenetrating polymer network hydrogels with different compositions of chitosan (Cs), acrylic acid, and citraconic acid were synthesized via free‐radical polymerization with ethylene glycol dimethacrylate as a crosslinker. The variations of the swelling percentages of the hydrogels with time, temperature, and pH were determined, and Cs–poly(acrylic acid) (PAA) hydrogels were found to be most swollen at pH 7.4 and 37°C. Scanning electron micrographs of Cs–PAA and Cs–P(AA‐co‐CA)‐1 (Cs‐poly(acrylicacid‐co‐citraconir acid)^?1) were taken to observe the morphological differences in the hydrogels. Although the less swollen hydrogel, Cs–P(AA‐co‐CA)‐1, had a sponge‐type structure, the most swollen hydrogel, Cs–PAA, displayed a uniform porous appearance. Fluconazole was entrapped in Cs–P(AA‐co‐CA)‐1 and Cs–PAA hydrogels, and the release was investigated at pH 4.0 and 37°C. The kinetic release parameters of the hydrogels (the gel characteristic constant and the swelling exponent) were calculated, and non‐Fickian diffusion was established for Cs–PAA, which released fluconazole much more slowly than the Cs–P(AA‐co‐CA)‐1 hydrogel. A therapeutic range was reached at close to 1 h for both hydrogels. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Thermoresponsive/low‐fouling Zwitterionic hydrogel for controlled drug release

A controlled/ living free‐radical polymerization technique was introduced to prepared a homogeneous poly(N‐isopropylacrylamide)‐g‐poly(sulfobetaine methacrylate) hydrogel (RG) possessing a highly porous architecture via two steps. Compared to a poly(N‐isopropylacrylamide)‐co‐poly(sulfobetaine methacrylate) hydrogel (CG) prepared by conventional radical polymerization, RG exhibited a much faster shrinking rate (it lost over 72% of the water in 15 min) in response to the temperature changes. The release behaviors of tetracycline hydrochloride (TCHC) of the hydrogels indicated the TCHC release from the RG could be prolonged to 48 h at 37°C; this was much longer than that for CG (5 h at 37°C). Bovine serum albumin (BSA) was chosen as the model protein to examine the low‐fouling properties of the RG. The BSA adsorption data showed that improved antifouling properties could be achieved by the RG at both 25 and 37°C. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39816.     

Synthesis and Characterization of Temperature-Sensitive Poly(N-isopropylacryamide) Hydrogel with Comonomer and Semi-IPN material

A series of temperature and pH sensitive hydrogels were synthesized using N-isopropylacrylamide (NIPAAm) as main monomer, sodium alginate (SA) as semi-IPN material, ethyl acrylate (EA) and acrylic acid (AA) as comonomer, and N-maleyl chitosan (N-MACH) as cross-linker. The temperature and pH sensitive behavior, swelling/deswelling kinetics of the hydrogels were investigated. And the mechanism of the phase transition was summed up. Sodium alginate/Poly(N-isopropylacryamide) semi-interpenetrating polymer network (SA/PNIPAAm semi-IPN) hydrogels exhibited a lower critical solution temperature (LCST) at about 32 °C with no significant deviation from the conventional PNIPAAm hydrogels. Poly(N-isopropylacryamide-co-ethyl acrylate) (P(NIPAAm-co-EA)) hydrogels exhibited LCST at 29–31°C, increasing the amount of EA in the hydrogel gradually decreased the LCST. Poly(N-isopropylacryamide-co-acrylic acid) [P(NIPAAm-co-AA)] hydrogels exhibited LCST at 34–39°C, with decreasing NIPAAm/AA from 96/4 to 92/8 and 90/10, the LCST increased from 34°C to 37°C and 39°C. In the swelling/deswelling kinetics, all the dried hydrogels exhibited fast swelling/deswelling behavior, which might be attributed to macroporous structures of the hydrogels.     

Evaluation of a water-resistant and biocompatible adhesive with potential use in bone fractures

The use of osteosynthesis materials when complex fractures are presented is well known. However, the use of these materials has not achieved a correct fixation and reduction of all bone fragments. Therefore, an adhesive for bones would provide a simple and quick method to fix this kind of fractures. The aim of this work is to propose and to evaluate an adhesive based on chitosan hydrogels that could have a potential use as a bone adhesive underwater and will not develop cytotoxic effects. Ionically and covalently crosslinked hydrogels based on chitosan were used in this study. Butt joint test with bovine cancellous bone specimens were used in order to measure the tensile bond strength (TBS) in ideal (completely dry) and physiological (immersed in water at 37 °C) conditions. Additionally, TBS was estimated as a function of time of bone specimens immersed in water at 37 °C. Cell viability was studied using MTT assay and cell morphology on the adhesive surface was examined by scanning electron microscope. Mechanical studies revealed that only covalently crosslinked hydrogels maintain their TBS at physiological condition with respect to the dry environment. In addition, it was observed that the TBS, using only covalently crosslinked hydrogels adhesives, dramatically changes as a function of time and its behavior increases as calcium carbonate and hydroxyapatite is added. Finally, in vitro cell testing of covalently crosslinked hydrogel with calcium carbonate and hydroxyapatite exhibited excellent biocompatibility. Therefore, this formulation is proposed as a potential candidate for clinical use in orthopedic surgery.