Controlled release of paclitaxel from biodegradable unsaturated poly(ester amide)s/poly(ethylene glycol) diacrylate hydrogels

Biodegradable hydrogels (FPBe-G) were synthesized by the photopolymerization of two precursors: FPBe, a fumurate-based unsaturated poly(ester amide) (UPEA), and poly(ethylene glycol) diacrylate (PEG-DA). Depending on the feed ratio of these two precursors, the resultant FPBe-G hydrogels showed different crosslinking levels of network structure, mesh sizes (ξ) and matrix morphology. When a lipophilic drug, paclitaxel, was preloaded into FPBe-G hydrogels, the two-month drug-release kinetics from FPBe-G hydrogels in both pure PBS buffer and α-chymotrypsin media were measured. The paclitaxel-preloaded FPBe-G hydrogels in a α-chymotrypsin solution had significantly faster drug release rate than the corresponding hydrogels in a pure PBS buffer due to an enzyme catalyzed biodegradation of FPBe-G hydrogels. Sustained paclitaxel releases over a two-month period without initial burst release were also achieved by using hydrogels having certain feed ratios of hydrogel precursors. These paclitaxel release data correlated well with the molecular mesh size (ξ), molecular weight between cross-links (M _c) and matrix morphological structure of FPBe-G hydrogels.     

Controlled release of paclitaxel from biodegradable unsaturated poly(ester amide)s/poly(ethylene glycol) diacrylate hydrogels

Biodegradable hydrogels (FPBe-G) were synthesized by the photopolymerization of two precursors: FPBe, a fumurate-based unsaturated poly(ester amide) (UPEA), and poly(ethylene glycol) diacrylate (PEG-DA). Depending on the feed ratio of these two precursors, the resultant FPBe-G hydrogels showed different crosslinking levels of network structure, mesh sizes (xi) and matrix morphology. When a lipophilic drug, paclitaxel, was preloaded into FPBe-G hydrogels, the two-month drug-release kinetics from FPBe-G hydrogels in both pure PBS buffer and alpha-chymotrypsin media were measured. The paclitaxel-preloaded FPBe-G hydrogels in a alpha-chymotrypsin solution had significantly faster drug release rate than the corresponding hydrogels in a pure PBS buffer due to an enzyme catalyzed biodegradation of FPBe-G hydrogels. Sustained paclitaxel releases over a two-month period without initial burst release were also achieved by using hydrogels having certain feed ratios of hydrogel precursors. These paclitaxel release data correlated well with the molecular mesh size (xi), molecular weight between cross-links (M(c)) and matrix morphological structure of FPBe-G hydrogels.     

Synthesis and water-swelling of thermo-responsive poly(ester urethane)s containing poly(epsilon-caprolactone), poly(ethylene glycol) and poly(propylene glycol)

Thermo-responsive multiblock poly(ester urethane)s comprising poly(epsilon-caprolactone) (PCL), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments were synthesized. The copolymers were characterized by GPC, NMR, FTIR, XRD, DSC and TGA. Water-swelling analysis carried out at different temperatures revealed that the bulk hydrophilicity of the copolymers could be controlled either by adjusting the composition of the copolymer or by changing the temperature of the environment. These thermo-responsive copolymer films formed highly swollen hydrogel-like materials when soaked in cold water and shrank when soaked in warm water. The changes are reversible. The mechanical properties of the copolymer films were assessed by tensile strength measurement. These copolymers were ductile when compared to PCL homopolymers. Young's modulus and the stress at break increased with increasing PCL content, whereas the strain at break increased with increasing PEG content. The results of the cytotoxicity tests based on the ISO 10993-5 protocol demonstrated that the copolymers were non-cytotoxic and could be potentially used in biomedical applications.     

Synthesis and characterization of poly(ethylene glycol)-poly(D,L-lactide-co-glycolide) poly(ethylene glycol) tri-block co-polymers modified with collagen: a model surface suitable for cell interaction

This study focused on the synthesis and characterization of poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) tri-block co-polymer (PEG-PDLLG-PEG), and its modification with type-I collagen. To this aim, a PEG-PDLLG-PEG tri-block co-polymer was synthesized in two steps by reacting poly(ethylene glycol)bis(carboxymethyl)ether with thionyl chloride to obtain an acyl-halide-terminated poly(ethylene glycol) and subsequently coupling this compound to hydroxyl-terminated poly(D,L-lactide-co-glycolide) (PDLLG). The new carboxyl endgroups of PEG-PDLLG-PEG were subsequently reacted with N-hydroxysuccinimide (NHS) in the presence of the hetero-bifunctional cross-linking agent dicyclohexylcarbodiimide (DCC) in order to activate the co-polymer for coupling with collagen. PEG-PDLLG-PEG and its activated form PEG-PDLLG-NHS were characterized by Fourier transform infrared (FT-IR) and 1H-NMR spectroscopy. Molecular weights of the polymeric products were determined by SEC. Type-I collagen in phosphate buffer was reacted with PEG-PDLLG-NHS. The resultant product, PEG-PDLLG-Col, was characterized by FT-IR. This biopolymer was used for preparation of a suitable surface for cell growth experiment. To measure the degree of cell proliferation, the films prepared with PDLLG, PEG-PDLLG-NHS and PEG-PDLLG-Col were seeded with L929 mouse fibroblasts. Cell growth was followed by SEM photography and quantitated by the neutral red uptake assay. It was shown that the attachment of collagen significantly increased the number of cells on the co-polymers.     

Functionalization of poly(ethylene glycol) and monomethoxy-poly(ethylene glycol)

Simple methods are described for the substitution of poly(ethylene glycol) and monomethoxy-poly(ethylene glycol) substitution. Affinity ligands, coenzymes, or enzymes can be covalently attached to the substitution product or they can be used as liquid ionexchangers.     

Room-temperature preparation and characterization of poly (ethylene glycol)-coated silica nanoparticles for biomedical applications

Monodisperse, spherical, polyethylene glycol (PEG)-coated silica nanoparticles have been prepared at room temperature and characterized for the purpose of biomedical applications. The particles were synthesized by the hydrolysis of tetramethyl orthosilicate (TMOS) in alcohol media under catalysis by ammonia, and their size can range from about 50-350 nm in diameter. We studied the particle size and size distribution using a scanning electron microscope (SEM) and an asymmetric field-flow fractionation (AFFF) multiangle static light-scattering instrument. The chemical and/or physical binding of PEG to the silica nanoparticles was studied by infrared spectroscopy, and the weight percentage of PEG attached to the particles was quantified. The PEG-coated silica nanoparticles showed enhanced colloidal stability when redispersed into aqueous solutions from the dried state as a result of the steric stabilization function of the PEG polymer grafted on the surface of particles. A nonspecific protein-binding test was also carried out to show that the PEG coating can help reduce the protein adsorption onto the surface of the particles, relating to the biocompatibility of these PEG-coated particles. Also, the inclusion of magnetic nanoparticles into the silica particles was shown as an example of the possible applications of PEG-coated silica particles. These silica nanoparticles, as a matrix for encapsulation of certain reagents, have potential for applications to in vivo diagnosis, analysis, and measurements inside intact biologic systems.     

Synthesis and characterization of functional elastomeric poly(ester amide) co-polymers

A new family of random co-poly(ester amides)s (co-PEAs) having reactive pendant functional carboxylic acid groups were synthesized by co-polycondensation of di-p-toluenesulfonic acid salts of bis-(L-alpha-amino acid (L-leucine and/or L-phenylalanine)) alpha,omega-alkylene diesters with active diesters of dicarboxylic acids using di-p-toluenesulfonic acid salt of L-lysine benzyl ester as a co-monomer. The lateral benzyl ester groups in the L-lysine segment of co-PEAs were subsequently transformed into free COOH groups by catalytic hydrogenolysis using Pd black as a catalyst. The co-PEA-based polyacids obtained, as well as the original co-PEA having lateral benzyl ester groups were characterized by standard methods. In vitro biodegradation studies in the presence of hydrolases like alpha-chymotrypsin and lipase showed significant enzymatic-catalyzed biodegradation of these co-PEAs. These co-PEA-based polyacids were used for covalent attachment of iminoxyl radicals (4-amino-TEMPO) and in vitro biodegradation of 4-aminoTEMPO attached polymer was studied along with releasing kinetic of iminoxyl radical.     

Synthesis and characterization of functional elastomeric poly(ester amide) co-polymers

A new family of random co-poly(ester amides)s (co-PEAs) having reactive pendant functional carboxylic acid groups were synthesized by co-polycondensation of di-p-toluenesulfonic acid salts of bis-(L-α-amino acid (L-leucine and/or L-phenylalanine)) α,ω-alkylene diesters with active diesters of dicarboxylic acids using di-p-toluenesulfonic acid salt of L-lysine benzyl ester as a co-monomer. The lateral benzyl ester groups in the L-lysine segment of co-PEAs were subsequently transformed into free COOH groups by catalytic hydrogenolysis using Pd black as a catalyst. The co-PEA-based polyacids obtained, as well as the original co-PEA having lateral benzyl ester groups were characterized by standard methods. In vitro biodegradation studies in the presence of hydrolases like α-chymotrypsin and lipase showed significant enzymatic-catalyzed biodegradation of these co-PEAs. These co-PEA-based polyacids were used for covalent attachment of iminoxyl radicals (4-amino-TEMPO) and in vitro biodegradation of 4-aminoTEMPO attached polymer was studied along with releasing kinetic of iminoxyl radical.     

Biodegradable poly(terephthalate-co-phosphate)s: synthesis, characterization and drug-release properties

To develop biodegradable polymers with favorable physicochemical and biological properties, we have synthesized a series of poly(terephthalate-co-phosphate)s using a two-step poly-condensation. The diol 1,4-bis(2-hydroxyethyl) terephthalate was first reacted with ethylphosphorodichloridate (EOP), and then chain-extended with terephthaloyl chloride (TC). Incorporation of phosphate into the poly(ethylene terephthalate) backbone rendered the co-polymers soluble in chloroform and biodegradable, lowered the Tg, decreased the crystallinity and increased the hydrophilicity. With an EOP/TC molar feed ratio of 80: 20, the polymer exhibited good film-forming property, yielding at 86.6 +/- 1.6% elongation with an elastic modulus of 13.76 +/- 2.66 MPa. This polymer showed a favorable toxicity profile in vitro and good tissue biocompatibility in the muscular tissue of mice. In vitro the polymer lost 21% of mass in 21 days, but only 20% for up to 4 months in vivo. It showed no deterioration of properties after sterilization by gamma-irradiation at 2.5 Mrad on solid CO2. Release of FITC-BSA from the microspheres was diffusion-controlled and exceeded 80% completion in two days. Release of the hydrophobic cyclosporine-A from microspheres was however much more sustained and near zero-ordered, discharging 60% in 70 days. A limited structure-property relationship has been established for this co-polymer series. The co-polymers became more hydrolytically labile as the phosphate component (EOP) was increased and the side chains were switched from the ethoxy to the methoxy structure. Converting the methoxy group to a sodium salt further increased the degradation rate significantly. The chain rigidity as reflected in the Tg values of the co-polymers decreased according to the following diol structure in the backbone: ethylene glycol > 2-methylpropylene diol > 2,2-dimethylpropylene diol. The wide range of physicochemical properties obtainable from this co-polymer series should help the design of degradable biomaterials for specific biomedical applications.     

Biodegradable and injectable paclitaxel-loaded poly(ester amide)s microspheres: fabrication and characterization

Novel biodegradable submicron microspheres of amino acid based poly(ester amide)s (PEAs) were fabricated by an oil-in-water (O/W) emulsion/solvent evaporation technique and their morphology and drug loading efficiency were examined. PEAs microspheres of mean diameter <1 microm with very narrow size distribution were obtained at a fair yield about 80%. The effects of PEA polymer concentration, polyvinyl alcohol emulsifier concentration, and the homogenizer speed on the size and morphology of final PEA microspheres were examined by analyzing their SEM images. It is found that a low PEA concentration, a high PVA concentration, and a high homogenizer speed are the optimal conditions for obtaining smaller microspheres. The biodegradation behaviors of these PEA microspheres at 37 degrees C were investigated as a function of enzyme (alpha-chymotrypsin) concentration and incubation time. The data showed similar surface erosion degradation mechanism as PEA polymers reported previously. Paclitaxel loaded PEA microspheres with high encapsulation efficiency were obtained without significantly affecting their size and surface morphology. The high drug loading efficiency close to 100% suggested that PEA microspheres may have the potential for the injection administration of highly hydrophobic anticancer drugs.     

Synthesis, characterization and cytotoxicity of poly(ethylene glycol)-graft-trimethyl chitosan block copolymers

PEGylated trimethyl chitosan (TMC) copolymers were synthesized in an attempt to both increase the solubility of chitosan in water, and improve the biocompatibility of TMC. A series of copolymers with different degrees of substitution were obtained by grafting activated poly(ethylene glycol)s (PEG) of different MW onto TMC via primary amino groups. Structure of the copolymers was characterized using 1H, 13C NMR spectroscopy and GPC. Solubility experiments demonstrated that PEG-g-TMC copolymers were completely water-soluble over the entire pH range of 1-14 regardless of the PEG MW, even when the graft density was as low as 10%. Using the methyl tetrazolium (MTT) assay, the effect of TMC molecular weight, PEGylation ratio, PEG and TMC molecular weight in the copolymers, and complexation with insulin on the cytotoxicity of TMC was examined, and IC50 values were calculated with L929 cell line. All polymers exhibited a time- and dose-dependent cytotoxic response that increased with molecular weight. PEGylation can decrease the cytotoxicity of TMC to a great extent in the case of low molecular weight TMCs. According to the cytotoxicity results, PEG 5 kDa is superior for PEGylation when compared to PEG 550 Da at similar graft ratios. Complexation with insulin further increased cell viability. In addition, Lactate dehydrogenase (LDH) assays were performed to quantify the membrane-damaging effects of the copolymers, which is in line with the conclusion drawn from MTT assay. Moreover, the safety of the copolymers was corroborated by observing the morphological change of the cells with inverted phase contrast microscopy. Based upon these results PEG-g-TMC merits further investigations as a drug delivery vehicle.     

Amphotericin B-loaded poly(ethylene glycol)-poly(lactide) micelles: preparation, freeze-drying, and in vitro release

Polymeric micelles prepared from a series of poly(ethylene glycol)-poly(lactide) (PEG-PLA) diblock copolymers with various PLA chain lengths were designed as drug carriers for water insoluble drug amphotericin B (AmB). Physicochemical properties of AmB-loaded micelles were evaluated. Micelles were freeze-dried to obtain long-time stable formulations. The redispersibility of the freeze-dried samples was poor when the weight ratio of PLA block was bigger than the PEG block of the copolymer. Various types of lyoprotectants including saccharides and PEGs with different molecular weight were tested to improve the redispersion performance of the freeze-dried samples. PEG was proved to be more effective than saccharides on stabilizing the micelles during lyophilization when the weight ratio of PLA block was bigger than PEG block. The sustained release in vitro of AmB was evidenced. About 80% of AmB was released in 80 h. The in vitro release behavior could be best described by the first-order equation. The release rate was reduced as enhancing PLA chain length due to the stronger interaction between poorly water-soluble AmB and longer hydrophobic chain length of PLA.     

Branched poly(ethylene glycol) linkers

Novel types of methoxy poly(ethylene glycol) (PEG) linkers (U-PEG linkers) have been synthesized. These PEG linkers are linear polymers that attach to bioactive agents via a functional group, derived from a 2° alcohol, located in the center of the polymer chain versus the traditional terminal attachment site. These new types of linkers can be prepared with different functional groups (e.g. active ester, succinimidyl carbonate, and carbazate) for selected point of attachment, including ethylene oxide oligomers to provide “stems” when steric factors need to be addressed. Conversion of p-nitrophenyl carbonates to the more desirable succinimidyl carbonates has also been accomplished by a novel nucleophilic displacement procedure. Modification of proteins with these reagents is easily accomplished and is illustrated by the conjugation of a U-PEG linker with L -asparaginase.     

Synthesis and characterization of tunable poly(ethylene glycol): gelatin methacrylate composite hydrogels

Poly(ethylene glycol) (PEG) hydrogels are popular for cell culture and tissue-engineering applications because they are nontoxic and exhibit favorable hydration and nutrient transport properties. However, cells cannot adhere to, remodel, proliferate within, or degrade PEG hydrogels. Methacrylated gelatin (GelMA), derived from denatured collagen, yields an enzymatically degradable, photocrosslinkable hydrogel that cells can degrade, adhere to and spread within. To combine the desirable features of each of these materials we synthesized PEG-GelMA composite hydrogels, hypothesizing that copolymerization would enable adjustable cell binding, mechanical, and degradation properties. The addition of GelMA to PEG resulted in a composite hydrogel that exhibited tunable mechanical and biological profiles. Adding GelMA (5%-15% w/v) to PEG (5% and 10% w/v) proportionally increased fibroblast surface binding and spreading as compared to PEG hydrogels (p<0.05). Encapsulated fibroblasts were also able to form 3D cellular networks 7 days after photoencapsulation only within composite hydrogels as compared to PEG alone. Additionally, PEG-GelMA hydrogels displayed tunable enzymatic degradation and stiffness profiles. PEG-GelMA composite hydrogels show great promise as tunable, cell-responsive hydrogels for 3D cell culture and regenerative medicine applications.     

Block copolymer of poly(ester amide) and polyesters: synthesis, characterization, and in vitro cellular response

In order to expand the properties and applications of aliphatic absorbable polyesters, a new biodegradable block copolymer family, poly(ester amide)-b-poly(ε-caprolactone) (PEA-b-PCL), was synthesized and characterized. These copolymers were synthesized by first preparing l-phenylalanine-based poly(ester amide) macroinitiators (Phe-PEAs) with free amine end groups via a solution polycondensation. The amine-terminated Phe-PEA macroinitiators were then used to initiate the ring-opening polymerization of ε-caprolactone monomer to prepare the PEA-b-PCL copolymers. The molecular weight (MW) of PEA-b-PCLs can be well controlled by adjusting the Phe-PEA MW and weight ratio of ε-caprolactone to Phe-PEA, and ranged from 7 to 50kgmol(-1). The copolymers' structure and properties were characterized by various physicochemical methods, such as nuclear magnetic resonance, gel permeation chromatography and solubility testing. The in vitro enzymatic biodegradation tests were performed to evaluate the biodegradation rate of the copolymers. The results showed that the introduction of Phe-PEA to PCL did not significantly change the degradation rate of PCL. Biological studies were conducted to assess the polymer's biological properties, like supporting the cell attachment and proliferation, and inflammation response. The results showed that the bovine aortic endothelial cells had very good attachment and proliferation performance on PEA-b-PCL coating surface. TNF-α release profiles showed that PEA-b-PCL exhibited a muted J774 macrophage inflammatory response.     

Preparation and characterization of ibuprofen-loaded poly(lactide-co-glycolide)/poly(ethylene glycol)-g-chitosan electrospun membranes

Ibuprofen-loaded composite membranes composed of poly(lactide-co-glycolide) (PLGA) and poly(ethylene glycol)-g-chitosan (PEG-g-CHN) were prepared by electrospinning. The electrospun membranes were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), mechanical evaluation and contact angle measurements. Shrinkage behavior of the membrane in buffer at 37 degrees C was also evaluated. It was found that PLGA glass transition temperature (Tg) decreased with increasing PEG-g-CHN content in the composite membranes, which results in a decrease in tensile stress at break but an increase in tensile strain of the membranes. The degree of shrinkage of these composite membranes decreased from 76 to only 3% when the PEG-g-CHN content in the membranes increased from 10 to 30%. The presence of PEG-g-CHN significantly moderated the burst release rate of ibuprofen from the electrospun PLGA membranes. Moreover, ibuprofen could be conjugated to the side chains of PEG-g-CHN to prolong its release for more than two weeks. The sustained release capacity of the PLGA/PEG-g-CHN composite membranes, together with their compliant and stable mechanical properties, renders them ideal matrices for atrial fibrillation.     

Preparation, characterization and properties of poly(2,2-dimethyl trimethylene carbonate-co-epsilon-caprolactone)-block-poly(ethylene glycol)

Degradable terpolymers were synthesized by bulk copolymerization of 2,2-dimethyl trimethyle necarbonate (DTC), epsilon-caprolactone (CL) and poly(ethylene glycol) (PEG) using stannous octoate as catalyst at 140 degrees C for 36 h. The molar ratio in feed of DTC to CL was fixed at 20:80. The molecular weight and the mol% of PEG were varied in order to obtain copolymers with different properties. The copolymers were characterized by 1H-NMR, 13C-NMR, FT-IR, GPC and DSC. It was found that the hydrophilicity of these materials increased with increasing PEG content in the copolymers, according to the measurements of static contact angles of distilled water on the surface of polymer films. Mechanical tests and hydrolytic degradation assays showed that copolymers of different degradability and mechanical properties could be tailored by adjusting the compositions. For the copolymer T-4 (11.9 mol% of PEG with Mn 2000), the tensile strength and the elastic modulus could reach 6.2 MPa and 25 MPa, respectively. It took only 4 weeks for the copolymer T-4 to degrade to 83% (M(n,t)/M(n,0)) and 10 weeks to 63% in 0.1 M PBS at pH 7.4 and 37 degrees C. There was no obvious acceleration of degradation rate in vivo in comparison with that in vitro. These materials might be useful for nerve regeneration guides and other biomedical applications.     

Microstructure and drug-release studies of sirolimus-containing poly(lactide-co-glycolide) films

Sirolimus-containing poly(lactide-co-glycolide) (PLGA) films were prepared by solution casting and removing the residual solvent, 1,4-dioxane, by liquid and supercritical carbon dioxide (CO(2) ) extraction. The effect of lactide:glycolide ratio, stereochemistry of PLGA, and extraction condition (i.e., temperature and pressure) on the polymer and drug morphologies was studied using wide-angle X-ray scattering and differential scanning calorimetry. The polymer and drug crystallinity increased after liquid and supercritical CO(2) extraction, and the level of drug crystallinity within the film depended on the extraction conditions. Generally, higher levels of drug crystallinity were observed in the films with amorphous polymer matrices, and the drug crystallinity increased with temperature and pressure of the extraction conditions. In vitro drug elution from these films was studied using a USP 4 apparatus. Polymer crystallinity was found to be the determining factor for drug release, whereby films with higher polymer crystallinity eluted less drug compared to films with amorphous polymer matrices.     

Poly(glutamic acid) poly(ethylene glycol) hydrogels prepared by photoinduced polymerization: Synthesis,characterization, and preliminary release studies of protein drugs

A class of new biodegradable hydrogels based on poly(ethylene glycol) methacrylate-graft-poly(glutamic acid) and poly(ethylene glycol) dimethacrylate was synthesized by photoinduced polymerization. Because all the polymeric constituents were highly hydrophilic, crosslinking could be performed in aqueous solutions. This type of crosslinked hydrogel was prepared by modifying a select number of acidic side-groups on poly(glutamic acid) with poly(ethylene glycol) methacrylate. These modified chains were then crosslinked in the presence of poly(ethylene glycol) dimethacrylate under a photoinduced polymerization at a wavelength of 365 nm. Swelling experiments were conducted to study the crosslinking density, pH-responsive behavior, and degradation of the hydrogel. Results showed that the degree of swelling of this type of hydrogels increased as the crosslinker concentration (or density) was reduced. Because of the presence of acidic side chains on poly(glutamic acid), swelling behavior was found to be pH-responsive, increasing at high pH in response to the increase in the amount of ionized acidic side chains. The degradation rate of these hydrogels also varied with pH. More rapid degradation was observed under stronger alkaline conditions because of the hydrolysis of the ester bonds between the crosslinker and the polymer backbone. Practically useful degradation rates could be achieved for such hydrogels under physiological conditions. Drug release rates from these hydrogels were found to be proportional to the protein molecular weight and the crosslinker density; increasing at lower protein molecular weight or crosslinker density. The preliminary findings presented in this article suggest that this class of biodegradable hydrogels could be an attractive avenue for drug delivery applications. The specific photoinduced crosslinking chemistry used would permit hydrogels to be synthesized in existence of the entrapped macromolecular drugs including peptides, proteins, and cells. In addition, the rapid feature of this polymerization procedure along with the ability to perform hydrogel synthesis and drug loading in an aqueous environment would offer great advantages in retaining drug activity during hydrogel synthesis.     

Preparation and characterization of poly(ethylene glycol) hydrogels cross-linked by hydrolyzable polyrotaxane

PEG hydrogels cross-linked by a hydrolyzable polyrotaxane were prepared and their hydrolytic erosion characterized in terms of supramolecular dissociation of the polyrotaxane. The hydrolyzable polyrotaxane, in which many α-cyclodextrins (α-CDs) are threaded onto a poly(ethylene glycol) (PEG) chain capped with L-phenylalanine via ester linkages, was used as a multifunctional cross-linker: the PEG network was covalently bound to hydroxyl groups of α-CDs in the polyrotaxane. The contact angle and water content of the hydrogels were varied with the polyrotaxane content in the feed. In vitro hydrolysis study revealed that the time to reach complete gel erosion was shortened by increasing the polyrotaxane content in the feed in relation to the decreased number of chemical crosslinks between PEG and α-CDs in the polyrotaxane. The hydrogel degradation in a physiological condition was found to be followed by bulk mechanism. These findings suggest that changing the preparative conditions such as polyrotaxane content will make it possible to control programmed gel erosion for tissue engineering.