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PubMed2000

Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate.

New injectable, in situ crosslinkable biodegradable polymer composites were investigated consisting of poly(propylene fumarate) (PPF), poly(ethylene glycol)-dimethacrylate (PEG-DMA), and beta-tricalcium phosphate (beta-TCP). We examined the effects of the PEG-DMA/PPF double-bond ratio and beta-TCP content on the crosslinking characteristics of the composites including the maximum crosslinking temperature and the gel point, as well as the properties of the crosslinked composites such as the compressive strength and modulus, and the water-holding capacity. The maximum crosslinking temperature was constant averaging 39.7 degrees C for the composite formulations tested. The gel points varied from 8.0 +/- 1.0 to 12.6 +/- 2.5 min and were not affected by the relative amounts of PEG-DMA. The compressive strength at yield of PEG-DMA/PPF composites without beta-TCP increased from 5.9 +/- 1.0 to 11.2 +/- 2.2 MPa as the double-bond ratio of PEG-DMA/PPF increased from 0.38 to 1.88. An increase in compressive modulus was also observed from 30.2 +/- 3.5 to 58.4 +/- 6.2 MPa for the same range of the PEG-DMA/PPF double-bond ratio. Also, the addition of beta-TCP (33 wt%) enhanced the mechanical properties of all composites. The equilibrium water content of networks without beta-TCP increased from 21.7 +/- 0.2 to 30.6 +/- 0.2% for a double-bond ratio of PEG-DMA/PPF ranging from 0.38 to 1.88. However, the mechanical properties of the swollen composites under compression were smaller than the dry ones. These data demonstrate the feasibility of fabricating injectable biodegradable polymer composites with engineered mechanical properties for orthopedic tissue engineering.

Acrylates↗
PubMed2002

Development of an injectable, in situ crosslinkable, degradable polymeric carrier for osteogenic cell populations. Part 2. Viability of encapsulated marrow stromal osteoblasts cultured on crosslinking poly(propylene fumarate).

The effect of temporary encapsulation of rat marrow stromal osteoblasts in crosslinked gelatin microparticles on cell viability and proliferation was investigated in this study for microparticles placed on a crosslinking poly(propylene fumarate) (PPF) composite over a 7 day time period. Encapsulated cells were seeded on crosslinking PPF composites at times up to 10 min following initiation of the crosslinking reaction, and also on fully crosslinked PPF composites and tissue culture polystyrene controls, with a cell seeding density of 5.3 x 10(4) cells/cm2. The crosslinked PPF composite exhibited an average gel point of 10.3 min and an average maximum crosslinking temperature of 47.5 degrees C. Cell viability and proliferation were assessed by DNA and 3H-thymidine assays and the results were compared with those for nonencapsulated cells. The results showed that the addition time of cells to a crosslinking PPF composite had a large effect on cell viability and proliferation for both encapsulated and nonencapsulated cells with more surviving cells added at later time points. Most importantly, the temporary encapsulation of cells significantly enhanced cell viability at earlier time points. The data indicate that the presence of gelatin microparticles does not affect the crosslinking of a PPF composite. They further suggest that the temporary encapsulation of cells in crosslinked gelatin microparticles may preserve the viability of cells contained in an actively crosslinking PPF composite used as an injectable polymeric scaffold serving also as a carrier for osteogenic cell populations.

Alkaline Phosphatase↗
PubMed2002

Development of an injectable, in situ crosslinkable, degradable polymeric carrier for osteogenic cell populations. Part 3. Proliferation and differentiation of encapsulated marrow stromal osteoblasts cultured on crosslinking poly(propylene fumarate).

This study investigated the effect of temporary encapsulation of rat marrow stromal osteoblasts in crosslinked gelatin microparticles on long-term cell proliferation and phenotypic expression for microparticles placed on crosslinking poly(propylene fumarate) (PPF) composites using N-vinyl pyrollidinone (N-VP) as a crosslinking agent over a 28 day time period. Encapsulated cells (ECs) were seeded on actively crosslinking PPF composites 6 min after initiation of the crosslinking reaction, and also on fully crosslinked PPF composites and tissue culture polystyrene controls, with a cell seeding density of 5.3 x 10(4) cells/cm2. Composites prepared with three PPF:N-VP ratios were examined: 1:0.5, 1:0.1, and 1:0.05. Samples were taken at specified time points and analyzed by DNA, 3H-thymidine, alkaline phosphatase, osteocalcin, and calcium assays, and the measurements were compared with those for nonencapsulated cells (NCs). The results showed that encapsulated marrow stromal cells exhibited much higher viability, proliferation, and phenotypic expression when placed on crosslinking PPF composites than NCs. The assay results for ECs on crosslinking PPF composites were also similar to those on fully crosslinked PPF composites. The data further demonstrated that the PPF:N-VP ratio had no effect on the viability, proliferation, or phenotypic expression of the ECs. These results suggest that cells encapsulated in crosslinked gelatin microparticles may be part of an injectable, in situ crosslinkable, biodegradable polymeric composite for bone tissue engineering applications.

Alkaline Phosphatase↗
PubMed2003

In vivo bone and soft tissue response to injectable, biodegradable oligo(poly(ethylene glycol) fumarate) hydrogels.

This study was designed to assess in vivo bone and soft tissue behavior of novel oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels using a rabbit model. In vitro degradation of the OPF hydrogels was also investigated in order to compare with in vivo characteristics. Four groups of OPF hydrogel implants were synthesized by alternation of crosslinking density, poly(ethylene glycol) (PEG) block length of OPF, and cell-binding peptide content. The in vitro degradation rate of OPF hydrogels increased with decreasing crosslinking density of hydrogels, which was characterized by measuring weight loss and swelling ratio of hydrogels and medium pH change. Examination of histological sections of the subcutaneous and cranial implants showed that an uniform thin circumferential fibrous capsule was formed around the OPF hydrogel implants. Quantitative evaluation of the tissue response revealed that no statistical difference existed in capsule quality or thickness between implant groups, implantation sites or implantation times. At 4 weeks, there was a very limited number of inflammatory and multinuclear cells at the implant-fibrous capsule interface for all implants. However, at 12 weeks, OPF hydrogels with PEG block length of number average molecular weight 6090+/-90 showed extensive surface erosion and superficial fragmentation that was surrounded by a number of inflammatory cells, while OPF hydrogels with PEG block length of number average molecular weight 930+/-10 elicited minimal degradation. Constant fibrous capsule layers and number of inflammatory cells were observed regardless of the incorporation of cell-binding peptide and crosslinking density of OPF hydrogels with PEG block length of number average molecular weight 930+/-90. These results confirm that the degradation of implants can be controlled by tailoring the macromolecular structure of OPF hydrogels. Additionally, histological evaluation of implants proved that the OPF hydrogel is a promising material for biodegradable scaffolds in tissue engineering.

Animals↗
PubMed2000

Osteoconductivity of an injectable and bioresorbable poly(propylene glycol-co-fumaric acid) bone cement.

We have investigated an injectable form of a resorbable bone cement based on in situ crosslinking of the unsaturated polyester, poly(propylene glycol-co-fumaric acid) (PPF). This material, filled with calcium gluconate/hydroxyapatite (CG/HA), cures to a hard cement degradable by hydrolysis. The purpose of this study was to evaluate the osteoconductive properties of this injectable cement. The cement was used as an adjunct to fixation with an intramedullary rod in the rat femoral osteotomy model. Ingrowth of new bone into the cement was examined in vivo. Negative and positive controls with rigid and loose internal fixation were included for comparison. Animals were evaluated histologically and histomorphometrically at 4 weeks postoperatively. Results of this study showed osteoblastic activity and new bone formation at the interface between the femoral bone and the cement in the experimental group. However, there was little bone remodeling at the endosteal surface in positive and negative controls. Histologic evaluation of the cement revealed the formation of cavitations, which likely resulted from leaching of the highly soluble calcium gluconate portion of the filler from the cement. These cavitations were sites of ingrowth of vascular and bony tissues. Intimate contact between the bone cement and the endosteal surface of the cortex was found. Quantitative histomorphometric analysis corroborated these observations. Findings of this study demonstrated the osteoconductivity of this type of injectable PPF-based bone cement.

Animals↗
PubMed2000

Marrow stromal osteoblast function on a poly(propylene fumarate)/beta-tricalcium phosphate biodegradable orthopaedic composite.

The objective of this study was to assess the osteoconductivity of a poly(propylene fumarate)/beta-tricalcium phosphate (PPF/beta-TCP) composite in vitro. We examined whether primary rat marrow stromal cells would attach, proliferate, and express differentiated osteoblastic function when seeded on PPF/beta-TCP substrates. Attachment studies showed that a confluent monolayer of cells had adhered to the substrates within an 8 h time frame for marrow stromal cells seeded at confluent numbers. Proliferation and differentiated function of the cells were then investigated for a period of 4 weeks for an initial seeding density of 42,000 cells/cm2. Rapid proliferation during the first 24 h as determined by 3H-thymidine incorporation was mirrored by an initial rapid increase in total cell number by DNA assay. A lower proliferation rate and a gradual increase in cell number persisted for the remainder of the study, resulting in a final cell number of 128,000 cells/cm2. Differentiated cell function was assessed by measuring alkaline phosphatase (ALP) activity and osteocalcin (OC) production throughout the time course. Both markers of osteoblastic differentiation increased significantly over a 4-week period. By day 28, cells grown on PPF/beta-TCP reached a maximal ALP activity of 11 (+/- 1) x 10(-7) micromol/min/cell, while the OC production reached 40 (+/- 1) x 10(-6) ng/cell. These data show that a PPF/beta-TCP composite exhibits in vitro osteoconductivity similar to or better than that of control tissue culture polystyrene.

Absorbable Implants↗
PubMed2002

Dosing and switching strategies for quetiapine fumarate.

BACKGROUND: The atypical antipsychotic agent quetiapine fumarate has demonstrated efficacy and tolerability in clinical trials in patients with chronic or subchronic exacerbations of schizophrenic symptoms. OBJECTIVE: This review summarizes clinical trial data and other practical information regarding the initiation and routine administration of quetiapine. Appropriate strategies for switching from other antipsychotic agents to quetiapine are also discussed. RESULTS: Quetiapine is an appropriate initial treatment for psychotic disturbances in patients with schizophrenia of any stage and for those in whom a therapeutic switch is indicated for clinical reasons, such as inability to tolerate the side effects of treatment. Titration to 400 mg/d is recommended using the following schedule, administered BID in divided doses: day 1, 50 mg; day 2, 100 mg: day 3, 200 mg; day 4, 300 mg; and day 5, 400 mg. In patients who respond to quetiapine, therapy should be continued at the optimal dose that maintains remission, within the range of 150 to 750 mg/d. When a change in therapy is indicated, several strategies for switching from one antipsychotic agent to another may be applied to switching to quetiapine. Whereas studies have shown that an abrupt switch to or withdrawal from quetiapine does not produce significant clinical consequences, in practice the switch should be carefully individualized to minimize the potential for psychotic relapse or development of withdrawal symptoms. CONCLUSIONS: Quetiapine has antipsychotic effects and good tolerability at doses from 150 to 750 mg/d. Patients can be switched to quetiapine and their treatment individualized to achieve the optimal therapeutic effect with a minimum of dose-limiting side effects. There are several strategies for switching to quetiapine from another antipsychotic agent that do not appear to cause significant exacerbation of psychosis or withdrawal reactions.

Adolescent↗
PubMed2003

In vitro release of transforming growth factor-beta 1 from gelatin microparticles encapsulated in biodegradable, injectable oligo(poly(ethylene glycol) fumarate) hydrogels.

This research investigates the in vitro release of transforming growth factor-beta1 (TGF-beta1) from novel, injectable hydrogels based on the polymer oligo(poly(ethylene glycol) fumarate) (OPF). These hydrogels can be used to encapsulate TGF-beta1-loaded-gelatin microparticles and can be crosslinked at physiological conditions within a clinically relevant time period. Experiments revealed that OPF formulation and crosslinking time may be adjusted to influence the equilibrium swelling ratio, elastic modulus, strain at fracture, and mesh size of these hydrogels. Studies with OPF-gelatin microparticle composites revealed that OPF formulation and crosslinking time, as well as microparticle loading and crosslinking extent, influence composite swelling. In vitro TGF-beta1 release studies demonstrated that burst release from OPF hydrogels with a mesh size of 136 A was approximately 53%, while burst release from hydrogels with a mesh size of 93 A was only 34%. For hydrogels with a large mesh size (136 A), encapsulation of loaded gelatin microparticles allowed burst release to be reduced to 29-32%, depending on microparticle loading. Likewise, final cumulative release after 28 days was reduced from 71% to 48-66% by encapsulation of loaded microparticles. However, inclusion of gelatin microparticles within OPF hydrogels of smaller mesh size (93 A) was seen to increase TGF-beta1 release rates. The equilibrium swelling ratio of the microparticle component of these composites was shown to be greater than the equilibrium swelling ratio of the OPF component. Therefore, increased release rates are the result of disruption of the polymer network during swelling. These combined results indicate that the kinetics of TGF-beta1 release can be controlled by adjusting OPF formulation and microparticle loading, factors affecting the swelling behavior these composites. By systematically altering these parameters, in vitro release rates from hydrogels and composites loaded with TGF-beta1 at concentrations of 200 ng/ml can be varied from 13 to 170 pg TGF-beta1/day for days 1-3 and from 7 to 47 pg TGF-beta1/day for days 6-21. Therefore, these studies demonstrate the potential of these novel hydrogels and composites in the sustained delivery of low dosages of TGF-beta1 to articular cartilage defects.

Capsules↗
PubMed1998

Chemopreventive potential of fumaric acid, N-acetylcysteine, N-(4-hydroxyphenyl) retinamide and beta-carotene for tobacco-nitrosamine-induced lung tumors in A/J mice.

Four agents, fumaric acid (FA), N-acetylcysteine (NAC), N-(4-hydroxyphenyl) retinamide (4-HPR) and beta-carotene (beta-CT), were evaluated for potential chemopreventive activity using the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor model in female A/J mice. The agents were evaluated in both 16-week and 52-week bioassays at two dose levels corresponding to 0.8 maximum tolerated dose (MTD) and 0.4 MTD administered throughout the bioassay either in the diet (FA, 160 and 80 mmol/kg diet; NAC, 160 and 80 mmol/kg diet; 4-HPR, 4 and 2 mmol/kg diet) or by subcutaneous injection twice a week (beta-CT, 32 and 16 mg/kg b.w.). Mice were treated with a single i.p. dose of 10 micromol NNK in saline 1 week after administration of test agent. Lung adenomas were evaluated in the 16-week bioassay, whereas both adenomas and adenocarcinomas of the lung were determined in the 52-week bioassay. Both bioassays showed that all four agents did not significantly inhibit the total tumor incidence and multiplicity of the lung. However, the incidence of adenocarcinomas was reduced (P < 0.01) at 52 weeks in NNK groups given either 0.8 MTD NAC or 0.8 MTD beta-CT compared with the NNK control group. The decreases in adenocarcinomas were accompanied by corresponding increases in adenomas in these treatment groups. Thus, this study showed that FA, NAC, 4-HPR and beta-CT did not inhibit the total tumor formation, however, at the higher doses both NAC and beta-CT significantly retarded the malignant progression in the lung of NNK-treated A/J mice.

Acetylcysteine↗
PubMed1998

Antihepatotoxic activity of monomethyl fumarate isolated from Fumaria indica.

Monomethyl fumarate, isolated for the first time from the methanolic extract of the whole plant of Fumaria indica, was characterised and screened for its antihepatotoxic activity in albino rats. The compound showed significant (P < 0.01) antihepatotoxic activity against thioacetamide in vitro, and against hepatotoxicities induced by carbon tetrachloride, paracetamol and rifampicin in vivo to an extent almost similar to that of silymarin, a known antihepatotoxic agent.

Acetaminophen↗
PubMed1999

Simultaneous determination of oxalic, fumaric, maleic and succinic acids in tartaric and malic acids for pharmaceutical use by ion-suppression reversed-phase high performance liquid chromatography.

A reliable method for the simultaneous determination of oxalic, fumaric, maleic, and succinic acids in tartaric and malic acids for pharmaceutical use by reversed-phase ion-suppression high performance liquid chromatography is presented. HPLC was achieved on a Nova-Pak C18 column by isocratic elution using water adjusted to pH 2.10-2.15 with perchloric acid, and detection was by UV adsorption at a wavelength of 210 nm. This method was found to be superior to previous liquid chromatography as well as other classical assay, and to be an attractive choice for the analysis of these compounds.

Chromatography, High Pressure Liquid↗
PubMed1999

Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic seroquel (quetiapine fumarate).

The interplay between dopamine and glutamate appears to be relevant in the etiopathology of schizophrenia. Although currently used antipsychotics do not interact with glutamatergic receptors, previous results have demonstrated that the expression profile of ionotropic glutamate receptors can be regulated by drugs such as haloperidol or clozapine. In the present investigation, the mRNA levels for NMDA and AMPA receptor subunits were measured after chronic treatment with the novel antipsychotic agent Seroquel (quetiapine fumarate, quetiapine) as compared to haloperidol and clozapine. Similarly to the prototype atypical clozapine, quetiapine reduced the mRNA expression for NR-1 and NR-2C, two NMDA forming subunits, in the nucleus accumbens. Furthermore, quetiapine, but not haloperidol or clozapine, increased the hippocampal expression for the AMPA subunits GluR-B and GluR-C. The differences between classical and atypical antipsychotics, as well as among the novel agents, might be relevant for specific aspects of their therapeutic activity and could provide valuable information for the role of glutamate in specific symptoms of schizophrenia.

Animals↗
PubMed1998

Attentional improvement following quetiapine fumarate treatment in schizophrenia.

This study examined changes in attentional performance in patients with schizophrenia during the 2 months after initiating treatment with quetiapine fumarate. Prior to treatment, attentional performance in patients with schizophrenia (n = 10) was significantly (p < 0.01) worse than in matched controls (n = 12). During treatment with quetiapine, performance in patients with schizophrenia improved, and by 2 months, did not differ significantly from that of the controls. These results suggest that quetiapine produces a significant improvement in attentional functioning in patients with schizophrenia.

Adult↗
PubMed2006

Effect of formoterol fumarate treatment on exercise-induced bronchoconstriction in children.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is common, particularly in children. OBJECTIVES: To compare the protective effect of single doses of formoterol fumarate via Aerolizer with placebo and albuterol in children with EIB. METHODS: In this randomized, double-blind, double-dummy, crossover trial, 23 children (aged 4-11 years) received formoterol, 12 or 24 microg; albuterol, 180 microg; or placebo at 4 separate visits. Protection against EIB was evaluated as the maximum percentage decrease in forced expiratory volume in 1 second (FEV1) from the preexercise value after exercise challenge tests (6-minute treadmill) conducted 15 minutes and 4, 8, and 12 hours after administration of the dose. RESULTS: The maximum percentage decrease in FEV1 after the 4-hour exercise test (primary efficacy variable) was significantly less for formoterol, 12 and 24 microg, vs placebo (P < .001 for both) or albuterol (P = .016 and .010, respectively); albuterol was not significantly different from placebo. Formoterol, 12 and 24 microg, differed from placebo at 8 hours (P = .002 and .001, respectively), with a smaller difference between albuterol and placebo (P = .045). Rescue medication use and a high dropout rate may have biased treatment differences at later time points. Protection against EIB (<20% maximum decrease in FEV1) across all time points was observed for 17 (77%) of 22 and 17 (74%) of 23 children with formoterol, 12 and 24 microg, respectively, compared with 8 (35%) of 23 with albuterol and 6 (27%) of 22 with placebo. CONCLUSIONS: Single doses of formoterol, 12 or 24 microg, are effective in protecting against EIB in children, affording a statistically significantly greater protective effect than placebo or albuterol.

Administration, Inhalation↗
PubMed1979

Diaspirins that cross-link beta chains of hemoglobin: bis(3,5-dibromosalicyl) succinate and bis(3,5-dibromosalicyl) fumarate.

Two double-headed aspirins, bis(3,5-dibromosalicyl) succinate and bis(3,5-dibromosalicyl) fumarate, have been found to be potent acylating agents of intracellular hemoglobin (A or S) in vitro. Furthermore, each of these reagents cross-links beta chains of hemoglobin, probably at the beta cleft. The modified hemoglobins show increased oxygen affinities and reduced gelation or sickling tendencies.

Acylation↗
PubMed2006

Deuterium isotope effects in the unusual addition of toluene to fumarate catalyzed by benzylsuccinate synthase.

The first step in the anaerobic metabolism of toluene is a highly unusual reaction: the addition of toluene across the double bond of fumarate to produce (R)-benzylsuccinate, which is catalyzed by benzylsuccinate synthase. Benzylsuccinate synthase is a member of the glycyl radical-containing family of enzymes, and the reaction is initiated by abstraction of a hydrogen atom from the methyl group of toluene. To gain insight into the free energy profile of this reaction, we have measured the kinetic isotope effects on Vmax and Vmax/Km when deuterated toluene is the substrate. At 30 degrees C the isotope effects are 1.7 +/- 0.2 and 2.9 +/- 0.1 on Vmax and Vmax/Km, respectively; at 4 degrees C they increase slightly to 2.2 +/- 0.2 and 3.1 +/- 0.1, respectively. We compare these results with the theoretical isotope effects on Vmax and Vmax/Km that are predicted from the free energy profile for the uncatalyzed reaction, which has previously been computed using density functional theory [Himo, F. (2002) J. Phys. Chem. B 106, 7688-7692]. The comparison allows us to draw some conclusions on how the enzyme may catalyze this unusual reaction.

Carbon-Carbon Lyases↗
PubMedDate not supplied

Synthesis and characterization of triblock copolymers of methoxy poly(ethylene glycol) and poly(propylene fumarate).

Amphiphilic block copolymers were synthesized by transesterification of hydrophilic methoxy poly(ethylene glycol) (mPEG) and hydrophobic poly(propylene fumarate) (PPF) and characterized. Four block copolymers were synthesized with a 2:1 mPEG:PPF molar ratio and mPEGs of molecular weights 570, 800, 1960, and 5190 and PPF of molecular weight 1570 as determined by NMR. The copolymers synthesized with mPEG of molecular weights 570 and 800 had 1.9 and 1.8 mPEG blocks per copolymer, respectively, as measured by NMR, representing an ABA-type block copolymer. The number of mPEG blocks of the copolymer decreased with increasing mPEG block length to as low as 1.5 mPEG blocks for copolymer synthesized with mPEG of molecular weight 5190. At a concentration range of 5-25 wt % in phosphate-buffered saline, copolymers synthesized with mPEG molecular weights of 570 and 800 possessed lower critical solution temperatures (LCST) between 40 and 45 degrees C and between 55 and 60 degrees C, respectively. Aqueous solutions of copolymer synthesized with mPEG 570 and 800 also experienced thermoreversible gelation. The sol-gel transition temperature was dependent on the sodium chloride concentration as well as the mPEG block length. The copolymer synthesized from mPEG 570 had a transition temperature between 40 and 20 degrees C with salt concentrations between 1 and 10 wt %, while the sol-gel transition temperatures of the copolymer synthesized from mPEG molecular weight 800 were higher in the range 75-30 degrees C with salt concentrations between 1 and 15 wt %. These novel thermoreversible copolymers are the first biodegradable copolymers with unsaturated double bonds along their macromolecular chain that can undergo both physical and chemical gelation and hold great promise for drug delivery and tissue engineering applications.

Biocompatible Materials↗
PubMedDate not supplied

In vitro cytotoxicity of injectable and biodegradable poly(propylene fumarate)-based networks: unreacted macromers, cross-linked networks, and degradation products.

This study evaluates the in vitro biocompatibility of an injectable and biodegradable polymeric network based on poly(propylene fumarate) (PPF) and the cross-linking agent PPF-diacrylate (PPF-DA). Using a methyl tetrazolium (MTT) assay, the effect of the concentrations of PPF and PPF-DA on the cytotoxicity of its unreacted macromers, cross-linked networks, and degradation products was examined. The influence of network structure properties on cell viability and attachment to the cross-linked material was also investigated. The unreacted macromers exhibited a time- and dose-dependent cytotoxic response that increased with more PPF-DA in the mixture. Conversely, the cross-linked networks formed with more PPF-DA did not demonstrate an adverse response because increases in conversion and cross-linking density prevented the extraction of toxic products. Fibroblast attachment was observed on the PPF/PPF-DA networks with the highest double bond conversions. The degradation products, obtained from the complete breakdown of the networks in basic conditions, displayed a dose-dependent cytotoxic response. These results show that there are concerns regarding the biocompatibility of injectable, biodegradable PPF/PPF-DA networks but also sheds light onto potential mechanisms to reduce the cytotoxic effects.

Absorbable Implants↗