Increasing Crosslinker Concentration Research Articles

Effect of Biodegradable Cross-Linkers on the Properties of the Novel Poly(NIPAAm) Hydrogels

In this article, a series of biodegradable cross-linkers, [poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l- lactide-co-glycolide), (PLGA-PEG-PLGA), diacrylate] (LGE dA) with different molar ratios of d,l-lactide (LA)/glycolide (GA) in PLGA, were prepared from the corresponding PLGA-PEG-PLGA diol (LGE diol) triblock copolymers and then acrylated with acryloyl chloride. The LGE diols were synthesized through ring-opening polymerization of LA and GA using PEG as an initiator and stannous octoate [Sn(Oct)2] as a catalyst in advance. A series of novel thermosensitive and biodegradable hydrogels were then prepared from N-isopropyl acrylamide (NIPAAm) and LGE dA as a cross-linker. The effect of different molar ratios of LA/GA in PLGA on the swelling ratio and physical properties of the poly(NIPAAm) hydrogels were investigated. The results showed that the swelling ratios of the poly(NIPAAm) hydrogels in deionized water decreased with increasing cross-linker content and increased with increasing GA content in the hydrogel. The compressive modulus and cross-linking density of the hydrogels also increased with an increase in the cross-linker content and molar ratio of LA/GA in the present hydrogel. The hydrogels can be degraded about 60% for the NL50 series of gels, but for NL78 about 53% can be degradable in 1-month biodegradable experiment. © 2012 Wiley Periodicals, Inc. Adv Polym Techn 32: E633–E650, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.21307

Preparation of pH- and ionic-strength responsive biodegradable fumaric acid crosslinked carboxymethyl cellulose

A novel biodegradable sodium carboxymethyl cellulose (NaCMC)-based hydrogel was synthesized by using fumaric acid (FA) as a crosslinking agent at various ratios. Hydrogels (CMCF) were characterized using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Swelling behaviors of hydrogels were investigated in distilled water, various salt, and pH solutions. The FTIR results indicated the crosslinking between carboxyl groups of FA with hydroxyl group of NaCMC through ester formation. AFM analyses showed that roughness of hydrogel surface decreased with increasing crosslinker concentration. The swelling capacity decreased with an increase in charge of the metal cation (Al3+<Ca2+<Na+). In order to investigate reversible pH sensitivity of CMCF hydrogels, pH-dependent swelling was studied at pH 2 and 10. Reversible pH-responsiveness of CMCF hydrogels was achieved. CMCF hydrogels containing the greatest ratio of FA exhibited the longest biodegradation time with a half life of 21h using cellulase.

Influence of environmental solution pH and microstructural parameters on mechanical behavior of amphoteric pH-sensitive hydrogels

Amphoteric hydrogels contain both ionizable acidic and basic groups attached on the polymer chains, which can change their volume in response to the slight alteration of the surrounding environmental p H. In this paper, a theory of equilibrium swelling of amphoteric p H-sensitive hydrogels which is an extension of the formalism proposed by Marcombe et al. and a new hybrid free-energy density function of amphoteric hydrogels composed of the Edwards-Vilgis slip-link model and the Flory-Huggins solution theory as well as the contributions of mixing the mobile ions with the solvent, and dissociating the acidic and basic groups are presented for the prediction of the influence of environmental solution p H, microstructural parameters and geometric constraints on mechanical behavior. The calculations were modeled on chitosan-genipin gels, and the results were compared to experimental data. Numerical calculations show that the model is able to predict the dependence of swelling on p H and crosslinker qualitatively well and quantitatively close to the experimental data. Each gel shows minimal swelling at low p H but an increase in swelling until a maximum was reached; for most of the p H range, a good fit was achieved except for where the maximum swelling occurs; for experimental data, the maximum swelling appears at about pH = 4 , but for modeled data the maximum swelling appears between pH = 4 and pH = 6 ; each gel swell decreasing with increasing crosslinker concentration was also successfully predicted. The calculated results also show that microstructural parameters and geometric constraints have a significant impact on the mechanical behavior of the amphoteric hydrogels; the gel swells less when the network is more densely entangled and the maximum swelling ratio of the gels under biaxial constraint is only about one-third of the maximum when the gels swell freely. The theory developed here is valuable for the design and optimization of a drug delivery system.

3-Mercaptopropionic Acid-Ce(IV) Redox Couple for Preparing Cross-Linked Gels with Moderate Swelling Ratios

3-Mercaptopropionic acid–Ce(IV) redox couple has been demonstrated to be useful for cross-linking polymerization of acrylamide (AAm) with N,N′-methylene bis(acrylamide) (MBAA). Effects of the cross-linker ratio, acid concentration, and Ce(IV) molar ratios on swelling behavior of the resulting hydrogels have been studied. These experiments show that increasing cross-linker content has greatly reduced the equilibrium swelling ratios as expected. Interestingly, the increase in the Ce(IV) concentration (nCe(IV)=nMPA) has resulted in a decrease in the swelling ratio. Because the thiol group in 3-mercaptosuccinic acid acts as a cross-linking agent, more cross-linking occurs with an increase in the Ce(IV) concentration and Ce(III) forming in the cross-linking polymerization reaction of AAm with MBAA may provide the formation of intermolecular complexes between amide groups in polymer chains; the swelling equilibrium ratio and swelling rate decrease with an increase in their concentrations in the cross-linking polymerization reaction of AAm with MBAA. Kinetics and equilibrium swelling values have been discussed in terms of reaction parameters. © 2012 Wiley Periodicals, Inc. Adv Polym Techn 32: E241–E248, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.21270

Influence of Chemical Cross-Linking on Properties of Gelatin/Chitosan Microspheres

Gelatin/chitosan (Gel/Cs) microspheres were prepared by water/oil (W/O) elusion with the use of chemical cross–linking agent of glutaraldehyde. The effects of cross-linking, including cross-linker concentration and cross-linking time, on the diameter, swelling ratio and cytotoxicity in-vitro of the microspheres were investigated. The results showed that the diameter of Gel/Cs microspheres decreased with increasing cross-linker content and cross-linking time period. Further, the swelling ratio of microspheres also decreased as increasing cross-linker content and cross-linking time. This indicated that the diameter and swelling ratio of the Gel/Cs microspheres can be achieved by controlling the amount of the cross-linking agent and the cross-linking time. The microsphere extracts with lower contents of glutaraldehyde (0.5 wt% and 1 wt%) were no toxic; however, the extract with 2.5 wt% of glutaraldehyde showed potential cytotoxicity.

Preparation and Properties of Polyvinyl Alcohol/Collagen Hydrogel

Hydrogel scaffolds based on poly(vinyl alcohol) (PVA) collagen films were prepared by a chemical cross-linking method. The effects of the contents of PVA and cross-linker on compressive strength and swelling ratio were studied, and the effect of the pH value of the immersion medium on the swelling ratio was also investigated. The results showed that the introduction of PVA improved the compressive strength of PVA/collagen hydrogel, and the swelling ratio of the hydrogel scaffold increased with increasing PVA content in the blends. With increasing cross-linker content, the swelling ratio decreased; however, the compressive strength increased. The swelling ratio of PVA/collagen scaffold increased when pH was decreased. In conclusion, swelling ratio and compressive strength in PVA/collagen blends can be controlled by variation of their contents, cross-linking agent content, and pH value.

Formulation and Characterization of Sodium Alginate g-Hydroxy Ethylacrylate Bio-Degradable Polymeric Beads: In Vitro Release Studies

Novel type of highly swollen beads were prepared by grafting 2-hydroxyethylacrylate onto biodegradable Sodium alginate (SA) via free-radical polymerization using potassium persulphate as an initiator and Triprolidine hydrochloride as a model drug. Evidence of grafting was obtained by fourier transform infrared spectroscopic technique. Morphological properties of the beads were studied by SEM analysis. Thermal properties and crystallinity of the beads were characterized using differential scanning calorimetry and thermogravimetric analysis and X-ray diffraction techniques, respectively. Dissolution experiments were performed to study the release profiles at 37 °C in phosphate buffer solution (pH-7.4). Effect of monomer content, crosslinking agent and drug/polymer ratio on swelling properties and release profiles were also comparatively studied. A dissolution result concludes that drug release decreases with increasing crosslinker content. The highest release (96%) was obtained for the beads prepared with 0.5 mL crosslinking agent. Equilibrium swelling degree also supports the drug release profiles confirming SA-g-HEA beads showed better release profiles compare to plain SA beads.

Shape memory polymer system of semi-interpenetrating network structure composed of crosslinked poly (methyl methacrylate) and poly (ethylene oxide)

Shape memory semi-interpenetrating polymer networks (semi-IPNs) composed of crystalline poly (ethylene oxide) (PEO) and crosslinked poly (methyl methacrylate) (x-PMMA) have been investigated. The selected compositions show shape memory property with a reasonable fast recovery (recovery time ∼1 min) and shape recovery ratio of 99%. Effects of composition (x-PMMA/PEO = 80/20…60/40) and crosslinker (triethyleneglycol dimethacrylate) concentration (up to 6 wt.%) on the creep property were also studied. The recovery time of the semi-IPNs increased and the creep compliance decreased with increasing crosslinker concentration. The network structure containing PEO crystal was characterized by scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) indicated that the PEO, present confined in the semi-IPN, melts at a lower temperature compared to the pure PEO. Dynamic mechanical analysis (DMA) showed a decrease in the glass transition (Tg) of the semi-IPN due to the phase mixing of amorphous PEO and PMMA. Both the glassy and rubbery moduli (Eg and Er, respectively) were lower for the semi-IPNs than for the x-PMMA network. On the other hand, the Eg/Er ratio was markedly increased for the semi-IPNs supporting an easy shaping along with a good shape fixing.

Composite hydrogels with temperature sensitive heterogeneities: influence of gel matrix on the volume phase transition of embedded poly-(N-isopropylacrylamide) microgels

The thermo-responsive behaviour of poly-(N-isopropylacrylamide) (PNiPAM) microgels embedded in covalently cross-linked non-temperature-sensitive polyacrylamide (PAam) hydrogel matrixes with different compositions was investigated by using small angle neutron scattering (SANS). The composition of the composite hydrogel was varied by (a) increasing the cross-linker and acrylamide concentration leading to strong hydrogel matrixes and (b) by increasing the microgel concentration to obtain composite gels with an internal structure. Additionally we synthesized composite hydrogels by using γ-irradiation as initiation for the polymerisation. This leads to the formation of chemical bonds between the PNiPAM microgels and the surrounding polyacrylamide matrix. Thus it is possible to synthesize hydrogels without an additional cross-linker, as well as pure particle networks. Some samples were prepared at two different temperatures, below and above the volume phase transition temperature of PNiPAM, resulting in highly swollen or totally collapsed microgels during the incorporation step. The volume phase transition of microgels is not influenced by a hydrogel matrix with high acrylamide concentration independent of the preparation temperature. However, an increased cross-linker concentration leads to a corset like constraint on microgel swelling. Microgels, which are embedded in the collapsed state (at 50 °C), are not able to swell upon cooling, whereas microgels embedded in the swollen state can collapse upon heating. For samples with an increased microgel concentration, the close microgel packing was disturbed by the formation of the polyacrylamide matrix. The hydrogel matrix squeezes the microgels together and leads to partial aggregation. The experiments demonstrate how composite hydrogels with stimuli-sensitive heterogeneities can be prepared such that the full responsiveness of the embedded microgels is retained while the macroscopic dimensions of the gel are not affected by the volume phase transition of the microgels.

Dynamic rheology studies of in situ polymerization process of polyacrylamide–cellulose nanocrystal composite hydrogels

A series of dynamic small-amplitude oscillatory shear experiments for in situ polymerization process of polyacrylamide–cellulose nanocrystal (PAM–CNC) nanocomposite hydrogels were performed to investigate the relationship between rheological properties and synthesis parameters including chemical cross-linker concentration, polymerization temperature, initiator concentration, and CNC aspect ratios. The results showed that CNCs accelerated the onset of gelation (tonset) and acted as a multifunctional cross-linker during the gelation reaction. The composite hydrogels exhibited enhanced steady-state elastic modulus \( \left( {G_\infty^\prime } \right) \) and plateau loss factor (tanδ) compared to these of the pure PAM hydrogels, indicating that adding CNCs not only reinforced but also toughened PAM hydrogels. \( \left( {G_\infty^\prime } \right) \) and the effective network junction density (N) increased with increased cross-linker concentration, polymerization temperature, and CNC aspect ratios, but decreased with increased initiator concentration. The changes of plateau tanδ were opposite to that of \( G_\infty^\prime \). The sol–gel transition kinetics of PAM–CNC hydrogels accelerated with increased cross-linker concentration and polymerization temperature and, however, reached optimization at 0.25 wt% of initiator concentration. CNCs with lower aspect ratios promoted tonset and the sol–gel transition of PAM–CNC hydrogels, suggesting the fact that CNCs with lower aspect ratios further facilitated the formation of network of PAM–CNC nanocomposite hydrogels.

Synthesis and properties of methacrylate‐based networked polymers having ionic liquid structures

AbstractMethacrylate‐based networked polymers having ionic liquid structures were prepared by radical copolymerization of methyl methacrylate (MMA) with multifunctional crosslinkers: ethyleneglycol dimethacrylate (EGDMA), trimethylolpropane trimethacrylate (TMPTMA), or triethyleneglycol dimethacrylate (TEGDMA), in the presence of 1‐ethyl‐3‐methylethyl‐1‐imidazolium bis(trifluoromethane)sulfonyl imide (EMImTFSI). The fundamental physical properties of several film samples prepared by varying the monomer composition and ionic liquid content were investigated. The obtained materials became turbid with increasing crosslinker content and ionic liquid content. Their ionic conductivity increased with increasing ionic liquid content, while it was almost independent of the crosslinker content. EGDMA‐derived materials and TMPTMA‐derived materials showed higher ionic conductivity than TEGDMA‐derived materials. TMPTMA‐derived materials showed higher thermal stability than EGDMA or TEGDMA‐derived materials. EGDMA and TMPTMA‐derived materials were stiffer than the TEGDMA‐derived materials. The elastic modulus of the film samples increased but the film became more brittle with the increase of crosslinker content. Scanning electron microscopy and atomic force microscopy observation revealed that phase separation of networked polymers and ionic liquid occurred in the highly crosslinked samples, and the phase separation structures became larger in scale with the increase of crosslinking density. This phase separation was considered to have a strong effect on the mechanical properties of the film samples. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

Maillard-Type Cross-Linked Soy Protein Hydrogels as Devices for the Release of Ionic Compounds: An In Vitro Study

The contribution of cross-linking degree on soy protein hydrogels release properties was studied in vitro using a Maillard-type cross linker and amaranth and methylene blue as tracers. Increased cross-linker concentration or salt presence in the gel generally led to decreased swelling/release rates in the absence of digestive enzyme. Surprisingly, at pH 1.2, amaranth was not released. In the presence of pepsin or pancreatin, increased cross-linker concentration or the presence of salt in the gel was also shown to decrease compound release, particularly for methylene blue at pH 7.5. Compound release was strongly dependent on medium pH and compound ionic status. Amaranth, an anionic molecule, showed slower release in gastric conditions, whereas methylene blue, a cationic drug, showed the opposite result. Partition coefficients of these compounds matched these results. This paper demonstrates the potential of food proteins as carriers of ionic compounds.

Kinetic study of swelling-induced surface pattern formation and ordering in hydrogel films with depth-wise crosslinking gradient

Hydrogels undergo extensive three-dimensional volume changes when immersed in water, the degree of which is determined by the network chemical composition and degree of crosslinking. When the hydrogel is attached to a rigid substrate, it swells preferentially perpendicular to the substrate. This anisotropic swelling generates a compressive stress, which drives the formation of surface patterns when exceeding a critical stress value (σ ≥ σc). In order to develop an indepth understanding of the mechanism of surface pattern formation in hydrogels, we investigated the dynamic evolution of surface patterns in photocured hydrogel films from poly(2-hydroxyethyl methacrylate) (PHEMA) crosslinked with different concentrations of ethylene glycol dimethacrylate (EGDMA, 0–3 wt%). During curing in the presence of oxygen, a modulus gradient along the film depth was generated due to oxygen inhibition of the radical polymerization near the film surface. The swelling-induced wrinkling pattern formation followed Fickian-type kinetics (λ ∼ t1/2) at early stages, which was independent of the final pattern morphology. The onset of wrinkling was found at a linear expansion of αc ≈ 1.12, which remained constant with increasing EGDMA concentration but decreased with increasing film thickness, indicating an increase in critical stress with crosslinker concentration. In contrast, the equilibrium linear expansion value, αe, decreased significantly (from 2.55 to 1.20) with increasing crosslinker concentration (from 0 to 3 wt%), resulting in transition from random patterns to highly ordered hexagonal structures.

Stress–strain behavior in main chain liquid crystalline elastomers: effect of crosslinking density and transverse rod incorporation on “Poisson's ratio”

AbstractStress–strain results are reported for two series of smectic C main chain liquid crystalline elastomers (MCLCEs). The structural variable in one series is crosslink density; in the other, transverse rod content. With increasing crosslinker content, the LCEs exhibit increased modulus, a shorter polydomain‐to‐monodomain (P–M) plateau, and a lower elongation at break. Increasing transverse rod content leads to lower clearing temperatures and lower modulus. For each series, stress–strain measurement was made simultaneously with Poisson's ratio determination. For the variable crosslinker series, typical behavior showed the Poisson's ratio increased at small strain, rose to a maximum about 50% strain, then decreased with greater strain. For the transverse rod series, typical behavior also showed the Poisson's ratio increased at small strain, rose to a maximum about 50% strain, then decreased with greater strain. In both series, the maximum in the Poisson's ratio corresponded to the onset of the P–M transition. Possible deformation mechanisms are presented.

Uptake of anionic gold nanoparticles by cationic microgel particles in dispersion: The effect of pH

The interactions of negatively charged gold nanoparticles with positively charged poly(2-vinylpyridine) microgel particles, initially in either their collapsed (pH 6) or swollen (pH 3) states, have been studied in aqueous dispersion. When the gold nanoparticles are mixed with the collapsed microgel particles, at pH 6, they adsorb around the surface of the microgel particles, having no appreciable affect on the size or structure of the microgel particles. However, this uptake of the anionic nanoparticles onto the surface of the microgel particles does lead to a reversal of the surface charge of the latter. When the gold nanoparticles are mixed with swollen cationic microgel particles at pH 3, the anionic gold nanoparticles are initially taken up into the interior of the cationic polymer network, due to electrostatic attraction. Addition of further gold particles leads to the (irreversible) collapse and reversal of sign of the microgel particles. The amount of gold particles absorbed into the interior of the microgel particles is found to decrease with increasing cross-linker content of the P2VP particles.

Enhanced insulin secretion of physically crosslinked pancreatic β-cells by using a poly(ethylene glycol) derivative with oleyl groups

A polymeric crosslinker was developed to promote the formation of cellular spheroids. Our approach was based on the crosslinking of cell membrane using a polymeric crosslinker that worked via hydrophobic interaction. The crosslinker, a poly(ethylene glycol) derivative with oleyl groups as a hydrophobic group at both ends, was synthesized and characterized by gel permeation chromatography and Fourier-transform infrared spectroscopy. Cell culture experiments were then performed to confirm spheroid formation. The rat pancreatic islet β-cell line RIN, which possesses the ability to secrete insulin, was cultured with the crosslinker in a round-bottomed 96-well plate. The formation of a spheroid was achieved when the crosslinker was added to the cell suspension, especially in the absence of serum. The size of the spheroid decreased with time and with increasing crosslinker concentration, and depended on the number of cells plated in each well. The number of cells cultured with crosslinker was almost constant during 7 days and hardly proliferated in crosslinker concentrations of 0–2.5 mg ml −1, while the number of cells showed a decrease in the 25 mg ml −1 crosslinker concentration. It was shown that the insulin protein secretion in the spheroid cultured with crosslinker for 1 week was enhanced. The cell adhesion protein E-cadherin mRNA expression of the resulting spheroid was also enhanced. These results indicate that the promoted cell function was due to the cell–cell and cell–matrix interactions in the spheroid, suggesting that this polymeric crosslinker was useful for the formation of cell spheroids.

Effects of glycerol co-solvent on the rate and form of polymer gel dose response

A factor currently limiting the clinical utility of x-ray CT polymer gel dosimetry is the overall low dose sensitivity (and hence low dose resolution) of the system. Hence, active research remains in the investigation of polymer gel formulations with increased CT dose response. An ideal polymer gel dosimeter will exhibit a sensitive CT response which is linear over a suitable dose range, making clinical implementation reasonably straightforward. This study reports on the variations in rate and form of the CT dose response of irradiated polymer gels manufactured with glycerol, which is a co-solvent that permits dissolution of additional bisacrylamide above its water solubility limit (3% by weight). This study focuses on situations where the concentration of bisacrylamide is kept at or below its water solubility limit so that the influence of the co-solvent on the dose response can be explored separately from the effects of increased cross-linker concentration. CT imaging and Raman spectroscopy are used to construct dose–response curves for irradiated gels varying in (i) initial total monomer (%T) and (ii) initial co-solvent concentration. Results indicate that: (i) for a fixed glycerol concentration, gel response increases linearly with %T. Furthermore, the functional form of the dose response remains constant, in agreement with a previous model of polymer formation. (ii) Polymer gels with constant %T and increasing co-solvent concentrations also show enhanced CT response. In addition, the functional form of the response is altered in these gels as co-solvent concentration is increased. Raman data indicate that the fraction of bis-acrylamide incorporated into polymerization, as opposed to cyclization, increases as co-solvent concentration increases. The changes in functional form indicate varying polymer yields (per unit dose), akin to relative fractional monomer/cross-linker (i.e. %C) changes in earlier studies. These results are put into context of the model of polymer formation. The implications of these results on the clinical utility of polymer gels with co-solvent are highlighted.

Ring‐opening metathesis polymerization of a modified linseed oil with varying levels of crosslinking

AbstractA commercial norbornyl‐functionalized linseed oil, blended with a bicyclic norbornene‐based crosslinking agent (at loadings ranging from 0 to 50 wt %) undergoes ring‐opening metathesis polymerization with the 1st generation Grubbs' catalyst to form a biorenewable polymer network. Comonomers are characterized, the thermal and mechanical properties of the cured systems are investigated by dynamic mechanical analysis, and thermal decomposition is evaluated by thermogravimetric analysis. The resin is shown to consist of a modified linseed oil and small oligomers of cyclopentadiene. Broad tan δ peaks suggest inhomogeneous phase morphologies, which result in complex crosslinking behaviors. The thermal stability of the polymers increases with increasing crosslinker content. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6851–6860, 2008

The Effect of Serum on the PEG-Based Crosslinker-Induced Spheroid Formation of Pancreatic β-Cell

A polymeric crosslinker poly(ethylene glycol) derivative with dioleyl groups as hydrophobic group at both ends was developed for promoting cellular spheroid formation. Our approach to bridge cells was based on the crosslinking of cell membrane using a crosslinker via the hydrophobic interaction. Using the crosslinker, spheroid formation of pancreatic β-cell line RIN in a round bottom 96-well plate was evaluated, especially in effect of serum on spheroid formation. In the presence or absence of serum, the size of prepared spheroid was found to decrease with increasing culture time and with increasing crosslinker concentration. However, the medium without serum proved to be a favorable condition for promoting cell aggregation because in this case spheroid with smaller size could be obtained. It was clarified that spheroid formation and insulin secretion of the spheroid prepared by the crosslinker were enhanced, especially in the medium without serum.

Characterization of alkali-treated collagen gels prepared by different crosslinkers

We have developed a naturally-derived crosslinker named malic acid derivative (MAD). In the present study, we prepared alkali-treated collagen (AlCol) gels with different crosslinkers including MAD and commercially available crosslinkers such as 1-ethyl-3-(3('-dimethylaminopropyl) carbodiimide (EDC) and glutaraldehyde (GA). There are named as AlCol-MAD, AlCol-EDC, and AlCol-GA. We then compared their physicochemical properties. The residual amino groups in AlCol-MAD were not detected at MAD concentrations higher than 30 mM. On the other hand, the residual amino groups in AlCol-EDC and AlCol-GA were detected at crosslinker concentrations of 30 mM. The swelling ratios of AlCol-MAD, AlCol-EDC, and AlCol-GA decreased with increasing crosslinker concentration. Enzymatic degradation rate of AlCol-GA was slower than that of AlCol-MAD and AlCol-EDC. The cytotoxicity of MAD was clearly lower than that of EDC and GA. The number of adhered L929 on AlCol-MAD was higher than on AlCol-EDC and AlCol-GA after incubation for 1 day. After the culture for 3 and 7 days, excellent growth of L929 was observed on AlCol-MAD. These results suggested that MAD was excellent crosslinker for the reactivity with amino groups and cytocompatibility. Therefore, the resulting AlCol-MAD has potential for various biomedical applications like tissue engineering scaffolds and carrier for drug delivery systems.