Material design for an artificial extracellular matrix: Cell entrapment in poly (N-isopropylacrylamide) (PNIPAM)-grafted gelatin hydrogel

As a thermoresponsive extracellular matrix, PNIPAM-derivatized gelatin (PNIPAM-gelatin) was synthesized by an iniferter-based graft polymerization of NIPAM on side chains of gelatin (molecular weight, ca. 9.5 ×10⁴ g/mol). The degree of grafting was 22.6 groups per molecule, and the estimated molecular weight of PNIPAM was ca. 1.2×10⁴ g/mol. The phase transition of dissolution/precipitation of PNIPAM-gelatin occurred at around 35°C. At concentrations above 15 w/v% over about 35°C, the solution was converted to hydrogel. The mechanical strength of the produced hydrogel increased with the concentration of PNIPAM-gelatin. The apparent elastic modulus of the hydrogel at a concentration of 20 w/v% was 1.2×10⁴Pa, which is nearly equal to that of collagen gel prepared at 0.15w/v%. When a culture medium containing the PNIPAM-gelatin (concentration, 20 w/v%) and bovine smooth muscle cells was incubated at 37°C, the cells were entrapped into a hydrogel. The entrapped cells apparently died in hydrogel with a thickness of 1 mm. However, the use of thinner hydrogel (thickness, 0.1 mm) or comixing with a small amount of PNIPAM-derivatized hyaluronic acid (PNIPAM-HA), even at 1 mm thickness, appeared to increase the survival of entrapped cells.     

Poly(N-isopropylacrylamide) (PNIPAM)-grafted gelatin as thermoresponsive three-dimensional artificial extracellular matrix: molecular and formulation parameters vs. cell proliferation potential

A series of poly(N-isopropylacrylamide)-grafted gelatins (PNIPAM gelatins) of three different graft densities (approx. 11, 22 and 34 graft chains per gelatin molecule) and three different molecular weights of their graft chains (molecular weight approximately 1.2 x 10(4), 5.0 x 10(4) and 1.3 x 10(5) g/mol) were prepared by multiple derivatization of dithiocarbamyl (DC) group in a gelatin molecule and subsequent iniferter (acts as an initiator, transfer-agent and terminator)-based photopolymerization of NIPAM. The weight ratio of PNIPAM graft chains to gelatin (P/G) varied from 1.4 to 49. Aqueous solutions of PNIPAM-gelatins showed thermo-responsiveness, depended on the graft density and the molecular weight of PNIPAM graft chain or P/G. Aqueous solutions (10 or 20%, w/v) of PNIPAM-gelatins with P/G of more than 5.8 were converted to gels at 37 degrees C. Focal plane images of PNIPAM-gelatin gels by confocal laser scanning microscopy revealed that the size of hydrophobically clustered aggregates increased with P/G, whereas the space of microvoids decreased with concentration. Compressive strain-stress measurements revealed that compressive strength of PNIPAM-gelatin increased with P/G. Bovine smooth muscle cells (SMCs)-entrapped gels were produced from PNIPAM-gelatin-containing cell-suspended medium solutions at 37 degrees C. The entrapped cells proliferated in the gel with P/G of more than 12. A higher cell proliferativity was obtained at low concentration (5%, w/v) and higher P/G (>18). Tissue formation composed of proliferative SMCs and cell-secreted extracellular matrices (collagen) was obtained at 14 days incubation. The inter-relationship between the molecular parameters of PNIPAM-gelatin, internal structural features and cell proliferation potential was discussed.     

Poly (N-isopropylacrylamide) (PNIPAM)-grafted gelatin as thermoresponsive three-dimensional artificial extracellular matrix: molecular and formulation parameters vs. cell proliferation potential

A series of poly(N-isopropylacrylamide)-grafted gelatins (PNIPAM gelatins) of three different graft densities (approx. 11, 22 and 34 graft chains per gelatin molecule) and three different molecular weights of their graft chains (molecular weight approximately 1.2 × 10⁴, 5.0 × 10⁴ and 1.3 × 10⁵ g/mol) were prepared by multiple derivatization of dithiocarbamyl (DC) group in a gelatin molecule and subsequent iniferter (acts as an initiator, transfer-agent and terminator)-based photopolymerization of NIPAM. The weight ratio of PNIPAM graft chains to gelatin (P/G) varied from 1.4 to 49. Aqueous solutions of PNIPAM-gelatins showed thermo-responsiveness, depended on the graft density and the molecular weight of PNIPAM graft chain or P/G. Aqueous solutions (10 or 20%, w/v) of PNIPAM-gelatins with P/G of more than 5.8 were converted to gels at 37°C. Focal plane images of PNIPAM-gelatin gels by confocal laser scanning microscopy revealed that the size of hydrophobically clustered aggregates increased with P/G, whereas the space of microvoids decreased with concentration. Compressive strain–stress measurements revealed that compressive strength of PNIPAM-gelatin increased with P/G. Bovine smooth muscle cells (SMCs)-entrapped gels were produced from PNIPAM-gelatin-containing cell-suspended medium solutions at 37°C. The entrapped cells proliferated in the gel with P/G of more than 12. A higher cell proliferativity was obtained at low concentration (5%, w/v) and higher P/G (> 18). Tissue formation composed of proliferative SMCs and cell-secreted extracellular matrices (collagen) was obtained at 14 days incubation. The inter-relationship between the molecular parameters of PNIPAM-gelatin, internal structural features and cell proliferation potential was discussed.     

The potential of poly(N-isopropylacrylamide) (PNIPAM)-grafted hyaluronan and PNIPAM-grafted gelatin in the control of post-surgical tissue adhesions

Poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAM-HA) and PNIPAM-grafted gelatin (PNIPAM-gelatin), which exhibit sol-to-gel transformation at physiological temperature, were applied as control of tissue adhesions: tissue adhesion prevention material and hemostatic aid, respectively. The rat cecum, which was abraded using surgical gauze, was coated with PNIPAM-HA-containing PBS (concentration: 0.5 w/v%). The coated solution was immediately converted to an opaque precipitate at body temperature, which weakly adhered to and covered the injured rat cecum. One week after coating, tissue adhesion between the PNIPAM-HA-treated cecum and adjacent tissues was significantly reduced as compared with that between non-treated tissue and adjacent tissues. On the other hand, the coating of bleeding spots of a canine liver with PNIPAM-gelatin-containing PBS (concentration: 20 w/v%) resulted in spontaneous gel formation on the tissues and subsequently suppressed bleeding. Although these thermoresponsive tissue adhesion prevention and hemostatic materials are still prototypes at this time, both thermoresponsive biomacromolecules bioconjugated with PNIPAM, PNIPAM-HA and PNIPAM-gelatin, may serve as a tissue adhesion prevention material and hemostatic aid, respectively.     

Poly(N-isopropylacrylamide)-grafted gelatin as a thermoresponsive cell-adhesive, mold-releasable material for shape-engineered tissues

Poly(N-isopropylacrylamide)-grafted gelatin (PNIPAM-gelatin) can be used as a thermoresponsive cell-adhesive matrix and mold-releasable material for shape-engineered tissues. An example of such a tissue with predetermined shape is realized by fabrication of a tubular endothelial cell construct. A solution containing a mixture of PNIPAM-gelatin and PNIPAM was coated on the luminal surface of a glass capillary tube. After air-drying, endothelial cells were seeded and cultured for four days at 37 degrees C. The infusion of the culture medium into the tube at 20 degrees C resulted in the spontaneous detachment and removal of a tubular vascular tissue composed of endothelial cells and supramolecularly organized extracellular matrices produced by endothelial cells on the basal side of the tissue. The potential use of a thermoresponsive cell-adhesive and mold-releasable material in complex-shaped tissue-engineered devices is discussed.     

System-engineered cartilage using poly(N-isopropylacrylamide)-grafted gelatin as in situ-formable scaffold: in vivo performance

Our previous study showed that cartilaginous tissue can be engineered in vitro with articular chondrocytes and poly(N-isopropylacrylamide)-grafted gelatin. This short-term in vivo study for cartilage repair was performed to screen a candidate method for a long-term study. In our previous in vitro study, however, two potential problems with the tissue-engineered cartilage were identified: (1). leakage of the transplant due to temperature decline and (2). concave deformation of transplant due to compressive loading. To solve these problems, we investigated in this study the usefulness of suturing with two different covering materials (periosteum or collagen film) and preculturing an engineered tissue for 2 weeks. PNIPAAm-gelatin-based engineered cartilage samples were evaluated at 5 weeks after operation by gross and microscopic examination. Leakage occurred only in specimens without precultured tissue and with a collagen film. Minimal surface deformation occurred in all specimens with precultured tissue. The score on gross examination showed that transplants with precultured tissue acquired a higher score than did the others. Histological evaluation showed a minimal foreign-body response of PNIPAAm-gelatin in all specimens and higher maturity as a cartilaginous tissue in specimens with precultured tissue. These results indicate that transplantation with precultured tissue may be a suitable method for a long-term in vivo study.     

Temperature-dependent modulation of blood platelet movement and morphology on poly(N-isopropylacrylamide)-grafted surfaces

Poly(N-isopropylacrylamide) (PIPAAm) exhibits a reversible, temperature-dependent soluble/insoluble transition at its lower critical solution temperature (LCST) of 32 degrees C in aqueous media. The temperature-responsive PIPAAm was grafted onto tissue culture polystyrene (TCPS) dish surfaces by electron beam irradiation. Blood platelet behaviors on PIPAAm-grafted surface were examined by computerized image analysis and scanning electron microscopy. Platelet behaviors on this surface were dramatically dependent upon temperature, but those on poly(ethylene glycol)(PEG)-grafted or polystyrene remained unchanged. Below the 32 degrees C (LCST), platelets on PIPAAm-grafted surfaces retained a rounded shape and an oscillating vibratory microbrownian motion for extended times, similarly to those on PEG-grafted surfaces. Above the LCST, platelets readily adhered, spread and developed characteristic pseudopodia on PIPAAm-grafted surface similarly to those on TCPS. An ATP synthesis inhibitor failed to hinder prevention of platelet adhesion onto PIPAAm-grafted surface (below the LCST) suggesting that the preventive mechanism is ATP-independent similarly to that of PEG-grafted surfaces. These results correlate platelet surface activation state with the hydration and structure of polymer surfaces, and demonstrate the ability to modulate such reactions by a small temperature change in situ.     

Two-dimensional manipulation of confluently cultured vascular endothelial cells using temperature-responsive poly(N-isopropylacrylamide)-grafted surfaces

Temperature-responsive hydration/dehydration changes in surface-grafted poly(N-isopropylacrylamide) (PIPAAm) were utilized for hydrophilic/hydrophobic surface property alterations in cell culture. In this report, we utilized PIPAAm-grafted surfaces to recover confluently-cultured vascular endothelial cells as coherent monolayers from this cell culture substrate and to transfer to new cell culture substrates. For this purpose, we used two different methods to recover and transfer cell monolayer cultures: (1) chitin membranes used as an apical side cell support during cultured cell transfer, allowing cell basal side reattachment to new culture substrates after transfer; and (2) a cell culture insert? (porous PET) used as both a support as well as new substrate, allowing basal surfaces of cultured cells to be exposed to the medium after transfer. In both cases, all cells grown on PIPAAm-grafted surfaces detach completely with maintenance of basement membrane-like structure. Recovered cells attach to the second culture surfaces, covering more than 60% of the new substrate, and retain approximately 90% viability and their original function as judged from tissue-type plasminogen activator secretion. This technique could be utilized to prepare novel bioartificial organs as well as cell co-culture systems by multi-layering different cell types to mimic tissue structures for tissue engineering.     

Poly(acrylic acid)-grafted Poly(N-isopropyl acrylamide) Networks: Preparation,Characterization and Hydrogel Behavior

Poly(acrylic acid)-grafted poly(N-isopropylacrylamide) co-polymer networks (PNIPAAm-g-PAA) were prepared via the reversible addition-fragmentation transfer (RAFT) polymerization of N-isopropyl- acrylamide (NIPAAm) with trithiocarbonate-terminated PAA as a macromolecular chain-transfer agent in the presence of N,N-methylenebisacrylamide. The PNIPAAm-g-PAA co-polymer networks were characterized by means of Fourier transform infrared spectroscopy, differential scanning calorimetry and small-angle X-ray scattering. It is found that the PNIPAAm-g-PAA co-polymer networks were microphase-separated, in which the microdomains of PNIPAAm-PAA interpolymer complexes were dispersed into the PNIPAAm matrix. The PNIPAAm-g-PAA hydrogels displayed a dual response to temperature and pH values. The thermoresponsive properties of PNIPAAm-g-PAA networks were investigated. Below the volume phase transition temperatures, the PNIPAAm-g-PAA hydrogels possessed much higher swelling ratios than control PNIPAAm hydrogel. In terms of swelling, deswelling and reswelling tests, it is judged that the PNIPAAm-g-PAA hydrogels displayed faster response to the external temperature changes than control PNIPAAm hydrogel. The improved thermoresponsive properties of hydrogels are ascribed to the formation of PAA-grafted PNIPAAm networks, in which the water-soluble PAA chains behave as the hydrophiphilic tunnels and allow water molecules to go through and, thus, to accelerate the diffusion of water molecules.     

In vivo evaluation of poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) (PNIPAM)-grafted gelatin as an in situ-formable scaffold

We examined whether poly(N-isopropylacrylamide)-grafted gelatin (PNIPAM-gelatin) with a lower critical solution temperature of approximately 34°C, which was prepared by quasi-living radical graft polymerization, can serve as an in situ-formable three-dimensional extracellular matrix or cell scaffold. A mixture of fibroblasts stained with fluorescent dye and PNIPAM-gelatin in Dulbeccos modified Eagles medium solution was injected into the subcutaneous tissue of Wistar rats, and immediately formed a white, opaque cell-incorporated gel. Fibroblasts immediately after injection were spherical in shape and were homogeneously distributed in the gel. Fibroblasts in the gel 2 weeks after injection had spread and proliferated. One day after injection, many macrophages and neutrophiles were observed around the gel. As the implantation period proceeded, the inflammation reaction subsided. One week after injection, fibroblasts in the native tissue and macrophages migrated into the gel. From 6 to 12 weeks after injection, some degree of calcification in the solid tissue was intermittently observed. The weight of the gel 6 weeks after implantation was reduced to almost one-half of the weight of the originally injected sample. The potential usefulness of PNIPAM-gelatin as an injectable scaffold is discussed.     

聚异丙基丙烯酰胺及其衍生物在组织工程中的应用

聚异丙基丙烯酰胺(PNIPAAm)是一种新型的智能高分子材料。PNIPAAm大分子侧链上由于同时具有亲水性的酰胺基和疏水性的异丙基而具有良好的温敏性能,同时它还显现出良好的生物相容性和无细胞毒性等特性,可作为理想的细胞外基质材料应用于组织工程领域。本文综述国内外关于PNIPAAm及其衍生物在组织工程中的研究及应用情况。     

Role of Thermo-responsiveness and Poly(ethylene glycol) Diacrylate Cross-link Density on Protein Release from Poly(N-isopropylacrylamide) Hydrogels

Thermo-responsive hydrogels have shown promise as injectable materials for local drug delivery. However, the phase-induced changes in polymer properties of N-isopropylacrylamide (NIPAAm) can pose additional challenges for achieving controlled protein release. In this work, thermo-responsive hydrogels derived from NIPAAm and cross-linked with poly(ethylene glycol) diacrylate (PEG-DA) were synthesized via free radical polymerization. The volume phase transition temperature (VPTT) of the hydrogels ranged from 32.9°C to 35.9°C. Below the VPTT, swelling ratios of the hydrogels decreased with cross-linker concentration, and showed a sharp drop (at least 4-fold) upon phase change. Protein encapsulation efficiency was high (84–90%) and decreased with cross-linker concentration. Release of bovine serum albumin, a model protein, at body temperature was significantly higher than at room temperature (67% at 37°C compared to 44% at 23°C after 48 h). The release kinetics of proteins from the hydrogels were initially expected to be a function of cross-link density. However, at the hydrogel compositions explored in this work, protein release did not change significantly with cross-linker mol fraction. The thermo-responsive hydrogels offer a promising platform for the localized delivery of proteins.     

Pulsatile peptide release from multi-layered hydrogel formulations consisting of poly(ethylene glycol)-grafted and ungrafted dextrans

Multi-layered hydrogel formulations consisting of poly(ethylene glycol)-grafted dextran (PEG-g-Dex) and ungrafted Dex were investigated as a model of pulsatile drug release. In these formulations, it is considered that the grafted PEG domains act as a drug reservoir dispersed in the Dex matrix based on aqueous polymer two-phase systems. The formulations exhibited surface-controlled degradation by dextranase, and insulin release was observed in a pulsatile manner because of the multi-layered structure: PEG-g-Dex hydrogel layers containing insulin and insulin-free Dex hydrogel layers. Thus, it is suggested that the multi-layered hydrogel formulations using PEG-g-Dex and Dex are feasible for chronopharmacological drug delivery systems.     

Pulsatile peptide release from multi-layered hydrogel formulations consisting of poly(ethylene glycol)-grafted and ungrafted dextrans

Multi-layered hydrogel formulations consisting of poly(ethylene glycol)-grafted dextran (PEG-g-Dex) and ungrafted Dex were investigated as a model of Pulsatile drug release. In these formulations, it is considered that the grafted PEG domains act as a drug reservoir dispersed in the Dex matrix based on aqueous polymer two-phase systems. The formulations exhibited surface-controlled degradation by dextranase, and insulin release was observed in a pulsatile manner because of the multi-layered structure, PEG-g-Dex hydrogel layers containing insulin and insulin-free Dex hydrogel layers. Thus, it is suggested that the multi-layered hydrogel formulations using PEG-g-Dex and Dex are feasible for chronopharmacological drug delivery systems.     

Thermo-Sensitive Hydrogels Based on Interpenetrating Polymer Networks Made of Poly(N-isopropylacrylamide) and Polyurethane

A series of interpenetrating polymer networks (IPNs) of vinyl-terminated polyurethane (VTPU) and poly(N-isopropylacrylamide) (PNIPAAm) was prepared by free radical polymerization. The effects of IPN composition and cross-linking density on the thermo-responsive and mechanical properties have been studied in terms of particle size, dynamic mechanical thermal properties, transmittance, swelling and de-swelling behavior and water transport mechanism. Results showed that the swelling ability of hydrogels increased over four orders of magnitude in terms of diffusivity, and phase transition became faster with increasing N-isopropylacrylamide (NIPAAm) content. Regarding the mechanical reinforcement of swollen gel, a significant increase in compression properties has been obtained by forming IPNs with polyurethane, which was tailor-made depending on the IPN composition and structure of polyurethane. Furthermore, a cross-linking density increase in the NIPAAm domain augmented rubbery modulus, decreased water swelling and increased water deswelling of the IPNs.     

Poly(N-isopropylacrylamide)-Based Polymers: Recent Overview for the Development of Temperature-Responsive Drug Delivery and Biomedical Applications

Temperature is a widely incorporated stimulus in pharmaceutical applications because of its efficiency as a therapeutic medium; thus, substantial evidence on temperature-responsive polymer applications is reported. Poly(N-isopropylacrylamide) (PNIPAAm) is a well-established, temperature-responsive polymer that exhibits a low critical solution temperature (LCST) at ≈ 32°C, which is close to physiological temperature. Hence, they are widely used in various pharmaceutical applications, such as drug delivery with nanocarriers and thermogels. Varying the LCST for different applications can be achieved by copolymerization with other hydrophobic or hydrophilic molecules, making it a favorable smart polymer. PNIPAAm is reported to enhance drug delivery by incorporation with nanocarriers and to facilitate prolonged drug delivery, thereby avoiding the burst release of drugs in temperature-responsive hydrogels. The application of PNIPAAm is not limited to drug delivery, and it is also applied in biomedical applications such as chromatography systems and cell culture applications, where its incorporation in cell culture media enhances cell production. The unique and versatile properties of PNIPAAm render it a promising smart polymer for various functional applications. Hence, this review focuses on the diverse applications of PNIPAAm.     

Raman spectroscopic study on water in aqueous solutions of temperature-responsive polymers: Poly(N-isopropylacrylamide) and poly[N-(3-ethoxypropyl)acrylamide]

A Raman spectroscopic study on property changes of water in the course of a temperatureresponsive solution-aggregate transition phenomenon of aqueous poly(N-isopropylacrylamide) and poly[N-(3-ethoxypropyl)acrylamide] solutions was carried out. Upon the transition of polymers from coil to globule followed by the aggregation of individual polymer chains, the height ratio of the the peaks at 3250 and 3 400 cm^?1, corresponding to the O? H stretching of water molecules, was drastically changed. Contribution of small water domains included in polymer aggregates (so-called interstitial water) to the change in the Raman spectra was suggested. Effects of polymer concentration and molecular weight of polymers on the spectra were also examined.     

Poly(epsilon-caprolactone) and poly(epsilon-caprolactone)-polyvinylpyrrolidone-iodine blends as ureteral biomaterials: characterisation of mechanical and surface properties,degradation and resistance to encrustation in vitro

This study describes the physicochemical properties and in vitro resistance to encrustation of solvent cast films composed of either poly(epsilon-caprolactone) (PCL), prepared using different ratios of high (50,000) to low (4000) (molecular weight) m.wt., or blends of PCL and the polymeric antimicrobial complex, poly(vinylpyrrolidone)-iodine (PVP-I). The incorporation of PVP-I offered antimicrobial activity to the biomaterials. Films were characterised in terms of mechanical (tensile analysis, dynamic mechanical thermal analysis) and surface properties (dynamic contact angle analysis, scanning electron microscopy), whereas degradation (at 37 degrees C in PBS at pH 7.4) was determined gravimetrically. The resistance of the films to encrustation was evaluated using an in vitro encrustation model. Reductions in the ratio of high:low-m.wt. PCL significantly reduced the ultimate tensile strength, % elongation at break and the advancing contact angle of the films. These effects were attributed to alterations in the amorphous content and the more hydrophilic nature of the films. Conversely, there were no alterations in Young's modulus, the viscoelastic properties and glass-transition temperature. Incorporation of PVP-I did not affect the mechanical or rheological properties of the films, indicative of a limited interaction between the two polymers in the solid state. Manipulation of the high:low m.wt. ratio of PCL significantly altered the degradation of the films, most notably following longer immersion periods, and resistance to encrustation. Accordingly, maximum degradation and resistance to encrustation was observed with the biomaterial composed of 40:60 high:low m.wt. ratios of PCL; however, the mechanical properties of this system were considered inappropriate for clinical application. Films composed of either 50:50 or 60:40 ratio of high:low m.wt. PCL offered an appropriate compromise between physicochemical properties and resistance to encrustation. This study has highlighted the important usefulness of degradable polymer systems as ureteral biomaterials.     

Efficacy of antibiotics-loaded interpenetrating network (IPNs) hydrogel based on poly(acrylic acid) and gelatin for treatment of experimental osteomyelitis: in vivo study

The safety and efficacy of gentamycin sulphate (GS)- or vancomycin hydrochloride (VCl)-loaded polymer devices based on poly(acrylic acid) and gelatin crosslinked selectively using 0.3 mol % N,N'-methylene bisacrylamide and 1 wt% glutaraldehyde were evaluated by varying the drug concentration onto the devices. The placebo and drug-loaded device of AxGx (acrylic acid:gelatin: 1:1 w/w) were employed for the treatment of experimental osteomyelitis in rabbit. Rabbits were categorized into four groups. Twelve rabbits in each group were treated with 12+/-1 mg of AxGx-1a (22% w/w GS), 12+/-1 mg of AxGx-1b (44% w/w GS), 16+/-1 mg of AxGx-1b (44% w/w GS) and 16+/-1 mg of AxGx-1c (44% w/w VCl). The drug concentration was measured following implantation in the adjacent tissue of femoral cavity, and serum. In femoral cavity maximum drug concentration was found on the 7th day with all the four types of devices. No drug was found after 21 days, at the local site with devices AxGx-1a and AxGx-1b (12+/-1 mg), whereas it was detected after 6 weeks with 16+/-1 mg device (44% w/w GS or VCl). Macroscopic evaluation after treatment revealed that swelling, redness, local warmth and drainage decreased depending upon the drug loading of the implants. Sequential radiographs, histology, microbiologic assay and scanning electron micrography demonstrated devices AxGx-1b and AxGx-1c (16+/-1 mg of 44% w/w drug loading) to be the most suitable device, which heals the infection after 6 weeks of treatment. No significant difference (p>0.05) in the rate of healing was observed between GS- and VCl-loaded devices. None of the implant showed toxic level of drug in serum at any given time.     

Poly(anhydride-ester) fibers: role of copolymer composition on hydrolytic degradation and mechanical properties

Poly(anhydride-esters), based on carboxyphenoxydecanoate (CPD), are biocompatible polymers that hydrolytically degrade. The mechanical properties of the poly(anhydride-esters) can be altered by copolymerization with para-carboxyphenoxyhexane (pCPH). Mechanical properties of three CPD:pCPH compositions (30:70, 40:60, and 50:50) are reported as a function of hydrolytic degradation. The mechanical characteristics evaluated were tensile modulus at 1% strain (E(1%)), tensile strength (sigma(B)), ultimate elongation (epsilon(B)), and toughness (E(r)). The 30:70 CPD:pCPH fibers maintained higher values for tensile modulus at all time points than the two other fiber compositions. In addition, the 30:70 CPD:pCPH fibers maintained lower values for both tensile strength and toughness than the two other fiber compositions. These phenomena resulted from the brittle nature of pCPH, the major component of the 30:70 CPD:pCPH fibers; increasing the pCPH concentration in the polymer lowers both tensile strength and toughness of the polymer by decreasing ductility. With increasing amounts of pCPH, the hydrolytic degradation occurred more slowly, as reflected in the copolymers' improved ability to retain their mechanical properties. Therefore, copolymerization is useful for controlling the mechanical properties of the fibers as well as the polymer degradation rate, which ultimately determines the rate at which physically or chemically encapsulated drugs can be released.