2D Porphyrin-Based Covalent-Organic Framework/PEG Composites: A Rational Strategy for Photocatalytic Hydrogen Evolution.

Two-dimensional porphyrin-based covalent-organic frameworks (2D-por-COFs) have gained significant attention as attractive platforms for efficient solar light conversion into hydrogen production. Herein, it is found that introducing transition metal zinc and polyethylene glycol (PEG) into 2D-por-COFs can effectively improve the photocatalytic hydrogen evolution performance. The photocatalytic hydrogen evolution rate of ZnPor-COF is 2.82 times higher than that of H2Por-COF. Moreover, ZnPor-COF@PEG has the highest photocatalytic hydrogen evolution efficiency, which is 1.31 and 3.7 times that of pristine ZnPor-COF and H2Por-COF, respectively. The filling of PEG makes the layered structure of COFs more stable. PEG reduces the distortion and deformation of the carbon skeleton after the experiment of photocatalytic hydrogen evolution. The layered stacking and crystallization of 2D-por-COFs are also enhanced. Meanwhile, the presence of PEG also accelerates the transfer of excited electrons and enhances the photocatalytic hydrogen evolution activity. This strategy will provide valuable insights into the design of 2D-por-COFs as efficient solid photocatalysts for solar-driven hydrogen production.

Taxanes hypersensitivity is not a risk factor for severe reactions to SARS-CoV-2 vaccines.

Summary: Background. Hypersensitivity reactions (HSR) to taxanes have been related to a complement activation by their excipients, polyoxyethylated castor oil and Polysorbate 80, structurally related to those of SARS-CoV-2 vaccines. The aim of this study was to verify the presence of a higher risk of HSR to SARS-CoV-2 vaccines in patients with history of HSR to taxanes. Methods. Patients with history of HSR to taxanes were evaluated before the vaccination in our center and underwent skin tests for PEG and Polysorbate 80 (PandP). Some patients completed the vaccination course in other centers without prior PandP skin tests because they had not manifested taxanes hypersensitivity before vaccination, or because those tests were not available. Results. 50 patients were evaluated. 100% of patients with history of hypersensitivity to taxanes completed the vaccine course with no cases of anaphylaxis. 33 underwent skin tests for PandP before the vaccination and no correlation was found between the positivity of PandP and taxanes skin tests (p = 0.538). 7 patients developed mild symptoms during skin tests and vaccination, similar but weaker than those suffered at the time of the taxane infusion, independently from the results of skin tests. Conclusions. In our cohort patients with history of reaction to taxanes were not at higher risk to develop anaphylaxis to SARS-CoV-2 vaccines. However, a common non-IgE mediated mechanism behind those HSRs cannot be completely excluded. This can only account for mild and harmless symptoms in case of SARS-CoV-2 vaccines. However, prudence is still recommended in these patients.

Assembly of an A6 L6 Anion Trigonal Antiprism and Binding of Glucopyranosides and Polyethylene Glycols (PEGs).

Anion-coordination-driven assembly (ACDA) has proven to be a very effective strategy for the construction of polyhedral structures. Here we demonstrate that variation of the "angle" of the backbone of C3 -symmetric tris-bis(urea) ligands, from triphenylamine to triphenylphosphine oxide, results in the change of the final construct from an A4 L4 tetrahedron to a higher-nuclearity, A6 L6 trigonal antiprism (A=anion, herein PO4 3- ; L=ligand). Most interestingly, this assembly features a huge hollow internal space that is divided into three compartments: one central cavity and two large outer pockets. This multi-cavity character enables the binding of different guests, namely monosaccharides or polyethylene glycol molecules (PEG600, PEG1000 and PEG2000), respectively. The results prove that anion coordination by multiple hydrogen bonds may provide both sufficient strength and flexibility, thus making possible the formation of complicated structures with adaptive guest binding ability.

Randomized trial of oral sulfate solution versus polyethylene glycol-ascorbic acid for bowel cleansing in elderly people.

BACKGROUND AND AIM: The efficacy and safety of the recently introduced low-volume purgatives in elderly people are not well known. Therefore, in this trial, we aimed to evaluate and compare the efficacy of two low-volume agents, oral sulfate solution (OSS) and 2-L polyethylene glycol with ascorbic acid (PEG-Asc), in elderly people. METHODS: A prospective, randomized, single-blinded, multicenter, non-inferiority trial was performed at three university-affiliated hospitals in South Korea. Outpatients aged 65-80 years, who underwent elective colonoscopy, were enrolled. The primary outcome was the rate of adequate bowel preparation assessed using the Boston Bowel Preparation Scale. RESULTS: A total of 199 subjects were randomized into the OSS (n = 99) or the 2-L PEG-Asc (n = 100) group. Of them, 189 subjects were included in the analysis of the primary outcome (OSS group 95 vs PEG-Asc group 94). The proportion of adequate bowel preparation was 89.5% (85/95) in the OSS group and 93.6% (88/94) in the 2-L PEG-Asc group. OSS was not inferior to 2-L PEG-Asc according to the prespecified non-inferiority margin of -15% (95% confidence interval for the difference, -12.1 to 3.8). Vomiting (11.6% vs 2.1%) and thirst (24.2% vs 11.7%) were more common in the OSS group than in the 2-L PEG-Asc group. CONCLUSIONS: OSS is an effective low-volume purgative that is non-inferior to 2-L PEG-Asc in elderly people. Both the low-volume agents were identified to be well tolerated and safe in the healthy elderly population.

Pre-administration of super-low volume polyethylene glycol is as effective as senna laxative as bowel preparation for colonoscopy: a randomized controlled phase 2 trial.

BACKGROUND AND PURPOSE: Senna laxatives are commonly used for bowel preparation before colonoscopies in Japan. However, this laxative frequently causes complications such as abdominal pain. This study aimed to establish a novel method of bowel preparation, which involved the pre-administration of super-low volume polyethylene glycol (PEG) for three days followed by the same-day administration of low volume PEG. METHODS: This study was a prospective, multicenter, investigator-blinded, phase 2, randomized control trial. The intake of 13.9 g (120 mL) of PEG or 1 g of a senna laxative for 3 days before the examination was indicated for each group, and 2 L of PEG solution was used for preparation on the examination day. The primary endpoint was the efficacy of bowel cleansing, as assessed by the Boston bowel preparation scale. The secondary endpoints were the adenoma detection rate and occurrence of complications. RESULTS: A total of 250 patients were initially enrolled. A total of 122 patients from each group were included in the intention-to-treat analysis. In the intention-to-treat analysis, the responder rates were the same for the two groups (56.6% vs 50.8%). Additionally, the adenoma detection rate did not differ between the two groups (34.9% vs 41.8%, P = 0.3795). In contrast, adherence was higher in the PEG group (93.4% vs 82.8%, P = 0.0101), and the occurrence of complications was lower in the PEG group (1.7% vs 16.4%, P = 0.0001). CONCLUSION: The novel super-low volume PEG method for bowel preparation was as effective as the conventional method with senna laxatives.

Modeling Binary and Multicomponent Systems Containing Supercritical CO2 with Polyethylene Glycols and Compounds Relevant to the Biodiesel Production.

The CPA equation of state is applied to model binary, ternary, and multicomponent mixtures that contain CO2 with polyethylene glycols or compounds relevant to biodiesel production, such as glycerol and various triglycerides. Effort has been made to evaluate the model performance on correlating both the liquid and the vapor phase compositions, which is a demanding task, revealing the model's and parameters' limitations, due to the rather low concentrations of heavy compounds in the vapor phase. Initially the model's binary parameters, which in all cases were temperature independent, were estimated using experimental data for binary systems. Those parameters were used to predict the phase behavior of supercritical CO2 containing ternary and multicomponent mixtures. Since no parameter was adjusted to ternary or multicomponent systems' data, the reported CPA results for such mixtures are considered as pure predictions. This is the final part of a series of studies [Tsivintzelis et al. Fluid Phase Equilibria 430 (2016) 75-92 and 504 (2020) 112337] that complete the parameterization of the CPA equation of state for systems relevant to the biodiesel production, which allows the application of the model to multicomponent mixtures of the relevant processes.

[Allergic reactions to COVID-19 vaccines: evidence and practice-oriented approach]. / Allergische Reaktionen auf COVID-19-Impfstoffe ­ Evidenz und praxisorientiertes Vorgehen.

Less than a year after the first detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccines have been approved for routine use in numerous countries and have already been used in mass vaccination programs. Vaccines include the mRNA BNT162b2 and mRNA 1273. Allergic reactions and anaphylaxis account for a substantial proportion of the adverse reactions to these vaccines observed to date, but overall they are rare. The incidence of anaphylaxis in the context of SARS-CoV­2 vaccination with the mRNA vaccines appears to be approximately 10-fold higher than with previous vaccines, at approximately 1 per 100,000 vaccine injections. One focus of the present article is a systematic review of the components of mRNA vaccines against " coronavirus disease 2019 " (COVID-19). Differences from established vaccines are addressed and the allergic potential of liposomes, polyethylene glycol, tromethamine/trometamol, and mRNA are discussed. Another focus is on the clinical presentation and course of allergic reactions to the COVID-19 vaccines. This is followed by a discussion of the therapeutic approach to anaphylactic reactions, as well as the drugs and medical supplies required to treat them. It is important to note that any vaccinee may be affected by anaphylaxis, regardless of whether or not allergic diseases are already known. Therefore, every vaccination site and every vaccinator must be prepared to recognize and treat severe allergic reactions.

Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals.

Polyethylene glycols are synthetic polymers composed of repeating oxyethylene subunits, which have been known for non-toxic, non-immunogenic, non-antigenic, good solubility in water and therefore approved for pharmaceutical applications. Recently, attachment or amalgamation of polyethylene glycols to therapeutic small molecules, peptides, proteins, or nanoparticles has become a mature technology for the sake of improving their pharmacokinetic and pharmacological profiles, also referred to as PEGylation. By comparison, there are only a few PEGylated pharmaceuticals have been registered for further clinical trials and even less was approved for marketing. High failure rate of PEGylated pharmaceuticals in pre-clinical and clinical trials could be majorly attributed to their unclear pharmacokinetic behaviors. Therefore, the in vivo fate of the PEGylated pharmaceuticals for the various routes of administration needs to be thoroughly investigated An accurate in vivo pharmacological study thereof highly depends on the precise detection of polyethylene glycols as well as their fragments in biological matrixes. The goal of this review is to highlight the analytical methods that were developed and applied to evaluate the polyethylene glycols in pharmaceutical ingredients and excipients, which bring us closer to bridging the gap between the development of polyethylene glycol-based drug delivery systems and their clinical application.

Polyethylene Glycol 35 (PEG35) Protects against Inflammation in Experimental Acute Necrotizing Pancreatitis and Associated Lung Injury.

Acute pancreatitis is an inflammatory disorder of the pancreas. Its presentation ranges from self-limiting disease to acute necrotizing pancreatitis (ANP) with multiorgan failure and a high mortality. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic, and water-soluble chemicals composed of repeating units of ethylene glycol. The present article explores the effect of PEG35 administration on reducing the severity of ANP and associated lung injury. ANP was induced by injection of 5% sodium taurocholate into the biliopancreatic duct. PEG35 was administered intravenously either prophylactically or therapeutically. Three hours after ANP induction, pancreas and lung tissue samples and blood were collected and ANP severity was assessed. To evaluate the inflammatory response, gene expression of pro-inflammatory cytokines and chemokine and the changes in the presence of myeloperoxidase and adhesion molecule levels were determined in both the pancreas and the lung. To evaluate cell death, lactate dehydrogenase (LDH) activity and apoptotic cleaved caspase-3 localization were determined in plasma and in both the pancreatic and lung tissue respectively. ANP-associated local and systemic inflammatory processes were reduced when PEG35 was administered prophylactically. PEG35 pre-treatment also protected against acute pancreatitis-associated cell death. Notably, the therapeutic administration of PEG35 significantly decreased associated lung injury, even when the pancreatic lesion was equivalent to that in the untreated ANP-induced group. Our results support a protective role of PEG35 against the ANP-associated inflammatory process and identify PEG35 as a promising tool for the treatment of the potentially lethal complications of the disease.

Formulation, Physiochemical, and Microbial Assay of Henna Oil Vaginal Suppository Formulated with Polyethylene Glycol Bases.

BACKGROUND: Persian Medicine is one of the oldest and richest complementary and alternative options in the field of medicine and has a comprehensive medical system. Henna oil is recommended in Persian Medicine for the treatment of numerous women's diseases such as cervicitis. To date, henna has been used for many medical purposes, including astringent, bleeding, cardioinhibitory, hypotension, and relaxation. Accordingly, the present study aimed to provide the formulation of a henna-oil-based vaginal suppository and examine its physicochemical and antimicrobial properties. METHODS: The present study was approved and performed in accordance with the regulations of Research Council, Kerman University of Medical Sciences, Kerman, Iran, in July 2016. Different percentages of henna oil, glycerin, and gelatin, as well as henna oil and polyethylene glycol 400 and 4000, were mixed to achieve a formulation with proper appearance features and, particularly, without any oil leakage from the suppository surface. Uniformity of weight, uniformity of content, disintegration time, and dissolution test of the suppositories were evaluated. The growth-inhibiting activity of the suppositories and aqueous extract of henna was evaluated against bacteria, including the Gram-positive bacterium Gardnerella vaginalis, Neisseria gonorrhoeae, and group B streptococcus. RESULTS: The formulations had a smooth appearance without any cracks or fractures. Disintegration times for glycero-gelatin and polyethylene glycol suppositories were 60 and 10 min, respectively. 40% of the drug was released from polyethylene glycol suppositories after 60 min, but glycero-gelatin suppositories had no release after three hours. Minimum inhibitory concentration (MIC) of suppositories and aqueous extract were 0.4 mg/mL and 0.01 mg/mL, respectively. CONCLUSION: Polyethylene glycol suppositories had acceptable physicochemical properties, and the henna extract and suppositories inhibited the three studied pathogens.

A novel volume-reduced CT colonography regimen using hypertonic laxative (polyethylene glycol with ascorbic acid): randomized controlled trial.

OBJECTIVES: The aim of this study is to investigate the feasibility of bowel preparation using a hypertonic laxative (polyethylene glycol with ascorbic acid, PEG + Asc) for CT colonography (CTC) and to examine the volume limit of laxative. METHODS: In one institution, patients who met the indications for CTC were enrolled and randomly assigned to CTC with regimen A (800 ml PEG + Asc), B (600 ml PEG + Asc), or C (400 ml PEG + Asc). Sodium diatrizoate was given orally for fecal tagging. On the previous day, patients ate low-residue meals and took the assigned lavage solution after dinner. A reader blinded to the preparation graded residual stool/fluid and fecal tagging quality in six segments of the colorectum. The primary outcome was a proportion of colon segments without stool. One hundred twenty segments in 20 patients with each regimen were needed to show a non-inferiority margin of 15%, assuming 85% of no stool. RESULTS: A total of 360 segments in 60 patients were analyzed. There were 83% of segments with no stool in regimen A, 89% in regimen B, and 88% in regimen C. Using the delta method, the 95% confidence interval of the risk difference (6.7%) between regimens A and B was - 2.2% to 15.6%, and the risk difference (5.0%) between regimens A and C was - 4.1% to 14%, both within the non-inferiority margin. Residual fluid and fecal tagging quality were also within the non-inferiority margin. No adverse events occurred. CONCLUSIONS: A novel CTC regimen using hypertonic laxative demonstrated optimal colon cleansing effectiveness even with the lowest volume of laxative (UMIN000022851). KEY POINTS: • A novel CTC regimen using a hypertonic laxative is feasible. • The lowest volume of laxative provides excellent colon imaging. • However, the lowest volume of laxative did not improve patient acceptance.

Monodisperse oligoethylene glycols modified Camptothecin, 10-Hydroxycamptothecin and SN38 prodrugs.

Camptothecin, which represents a class of natural products with high anticancer activity, suffers low water solubility which hampers its clinic application. To address this issue, monodisperse polyethylene glycols were employed to modify this class of natural products, including Camptothecin, 10-Hydroxycamptothecin, and SN38. Through selective modification with a series of monodisperse polyethylene glycols, 31 Camptothecin derivatives, including 9 ethers and 22 carbonates, were prepared using a macrocyclic sulfate-based strategy with high efficacy. Monodisperse polyethylene glycols modification provided the Camptothecin derivatives with high purity and fine-tunable water solubility. Through the physicochemical and biological assays, a few novel prodrugs with good solubility, cytotoxicity, and valuable drug release profile were identified as promising anticancer drug candidates.

Treatment failure in children diagnosed with constipation in a paediatric emergency department in relation to Rome III criteria.

OBJECTIVE: To determine if treatment failure varies based on ROME III classification and adherence to guideline congruent therapy among children diagnosed in an emergency department with functional constipation. METHODS: Children aged 1 month to 18 years who were diagnosed with constipation in a paediatric emergency department underwent chart review and 7-day phone follow-up to complete the ROME III questionnaire, confirm treatments administered, and assess treatment failure. Participants were classified according to the ROME III criteria as having functional constipation (FC) or irritable bowel syndrome - constipation (IBS-C) subtype. The primary outcome was treatment failure defined as ≥ 2 of the following: 1) presenting symptom persistence; 2) < 1 bowel movement every other day; 3) pain/difficulty passing stools; and 4) abdominal pain between bowel movements. RESULTS: Five hundred and thirteen children completed follow-up; 40% (204/513) had FC, 23% (118/513) IBS-C, and 37% (191/513) did not meet either criteria. Treatment failure rates in children who received guideline congruent treatment were 28% (38/135) among those classified as FC and 43% (37/86) among those with IBS-C; P=0.02, a difference of 15% (95% confidence interval [CI]: 0.02, 0.27). On regression analysis, ROME III classification was not an independent predictor of treatment failure (odds ratio [OR]: 1.56 [95% CI: 0.97, 2.51]). At 7-day follow up, pain in between bowel movements was present in 22% (44/204) in FC patients versus 45% (53/118) of IBS-C patients; P=0.001. CONCLUSIONS: Treatment failure rates in children who receive guideline congruent therapy are higher among those with IBS-C, however, after adjustment for known confounders the relationship was not statistically significant.

Thermoresponsive PEG-Coated Nanotubes as Chiral Selectors of Amino Acids and Peptides.

A series of nanotubes with a dense layer of short poly(ethylene glycol) (PEG) chains on the inner surface are prepared by means of a coassembly process using glycolipids and PEG derivatives. Dehydration of the PEG chains by heating increases the hydrophobicity of the nanotube channel and fluorescent-dye-labeled amino acids are extracted from bulk solution. Rehydration of the PEG chains by cooling results in back-extraction of the amino acids into the bulk solution. Because of the supramolecular chirality of the nanotubes, amino acid enantiomers can be separated in the back-extraction procedure, which is detectable with the naked eye as a change in fluorescence as the amino acids are released from the nanotubes. The efficiency and selectivity of the chiral separation are enhanced by tuning the chemical features and inner diameter of the nanotube channels. For example, compared with wide nanotube channels (8 nm), narrow nanotube channels (4 nm) provide more effective electrostatic attraction and hydrogen bond interaction environments for the transporting amino acids. Introduction of branched alkyl chains to the inner surface of the nanotubes enables chiral separation of peptides containing hydrophobic amino acids. The system described here provides a simple, quick, and on-site chiral separation in biological and medical fields.

Monodisperse oligoethylene glycols modified Propofol prodrugs.

The low water solubility of Propofol resulted in complicated formulation and adverse effects during its clinical application. To improve its water solubility and maintain its anesthetic effects, Propofol prodrugs with monodisperse oligoethylene glycols as solubility enhancer were designed and synthesized. Monodisperse oligoethylene glycols enable the concise manipulation of water solubility, biocompatibility and anesthetic effects. Through the physicochemical and biological assay, a few water soluble prodrugs of Propofol were identified as promising anesthetic to overcome the drawbacks associated with Propofol.

Application of Monodisperse PEGs in Pharmaceutics: Monodisperse Polidocanols.

Polydisperse PEGs are ubiquitously used in pharmaceutical industry and biomedical research. However, the monodispersity in PEGs may play a role in the development of safe and effective PEGylated small molecular drugs. Here, to avoid the polydispersity in polidocanol, the active ingredient in a clinically used drug, a macrocyclic sulfate-based strategy for the efficient and scalable synthesis of monodisperse polidocanols, their sulfates, and their methylated derivatives, was developed. TLC and HPLC analysis indicated a complex mixture in regular polidocanol and high purities in monodisperse polidocanols and their derivatives. Assay on HUVEC, L929, and HePG2 cells showed that monodisperse polidocanols have much higher cytotoxicity and safety than that of regular polidocanol. It was found that the monodispersity of PEGs in polidocanols is crucial for achieving the optimal therapeutic results. Therefore, based on this case study, it would be beneficial to optimize PEGylated small molecular drugs with monodisperse PEGs in pharmaceutical research and development.

Randomized trial comparing oral sulfate solution with 4-L polyethylene glycol administered in a split dose as preparation for colonoscopy.

BACKGROUND AND AIM: The present study aimed to evaluate the non-inferiority of low-volume oral sulfate solution (OSS) to 4-L polyethylene glycol (PEG) solutions administered in a split-dose regimen as bowel preparation for colonoscopy. The safety and tolerability were also compared between the two regimens. METHODS: In this prospective, randomized, single-blind, active-control, parallel group, and non-inferiority trial, consecutive outpatients and health checkup recipients aged 19-65 years undergoing elective colonoscopy were enrolled to receive OSS or 4-L PEG in a split-dose regimen. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. The occurrence of any adverse events, acceptance, compliance, and satisfaction during bowel preparation were evaluated by participant interviews. RESULTS: Overall, 210 participants were randomized, and 199 were administered by the study agents. Adequate bowel preparation was achieved in 98.0% (97/99) of the OSS group, which was non-inferior to the PEG group (96%; 96/100) with a difference of +2.8% (95% confidence interval; -2.8, +6.8). There were no differences in the incidence of adverse events except for abdominal pain, which was more frequent in the OSS (7.1%, 7/99) than in the PEG (1.0%, 1/100; P = 0.035) group. Acceptance, compliance, and satisfaction were significantly higher in the OSS than in the PEG group (all P < 0.05). CONCLUSIONS: Split-dose OSS was non-inferior to split-dose 4-L PEG with regard to bowel preparation efficacy before colonoscopy in adult outpatients or screening colonoscopy recipients aged ≤65 years with acceptable safety and superior tolerability.

Bone augmentation at peri-implant dehiscence defects comparing a synthetic polyethylene glycol hydrogel matrix vs. standard guided bone regeneration techniques.

OBJECTIVES: The aim of the study was to test whether or not the use of a polyethylene glycol (PEG) hydrogel with or without the addition of an arginylglycylaspartic acid (RGD) sequence applied as a matrix in combination with hydroxyapatite/tricalciumphosphate (HA/TCP) results in similar peri-implant bone regeneration as traditional guided bone regeneration procedures. MATERIAL AND METHODS: In 12 beagle dogs, implant placement and peri-implant bone regeneration were performed 2 months after tooth extraction in the maxilla. Two standardized box-shaped defects were bilaterally created, and dental implants were placed in the center of the defects with a dehiscence of 4 mm. Four treatment modalities were randomly applied: i)HA/TCP mixed with a synthetic PEG hydrogel, ii)HA/TCP mixed with a synthetic PEG hydrogel supplemented with an RGD sequence, iii)HA/TCP covered with a native collagen membrane (CM), iv)and no bone augmentation (empty). After a healing period of 8 or 16 weeks, micro-CT and histological analyses were performed. RESULTS: Histomorphometric analysis revealed a greater relative augmented area for groups with bone augmentation (43.3%-53.9% at 8 weeks, 31.2%-42.8% at 16 weeks) compared to empty controls (22.9% at 8 weeks, 1.1% at 16 weeks). The median amount of newly formed bone was greatest in group CM at both time-points. Regarding the first bone-to-implant contact, CM was statistically significantly superior to all other groups at 8 weeks. CONCLUSIONS: Bone can partially be regenerated at peri-implant buccal dehiscence defects using traditional guided bone regeneration techniques. The use of a PEG hydrogel applied as a matrix mixed with a synthetic bone substitute material might lack a sufficient stability over time for this kind of defect.

Biodegradation and tissue integration of various polyethylene glycol matrices: a comparative study in rabbits.

OBJECTIVES: To test whether or not chemical and/or physical modifications of polyethylene glycol (PEG) hydrogels influence degradation time, matrix/membrane stability, and integration into surrounding hard and soft tissues. MATERIAL AND METHODS: In 28 rabbits, six treatment modalities were randomly applied to six sites on the rabbit skull: a dense network PEG hydrogel (PEG HD), a medium-dense network PEG hydrogel (PEG MD), a medium-dense network PEG hydrogel modified with an RGD sequence (PEG MD/RGD), a medium-dense network PEG hydrogel modified with RGD with reduced carboxymethyl cellulose (PEG MD/RGD_LV), a loose network PEG hydrogel modified with RGD (PEG LD/RGD), and a collagen membrane (BG). Descriptive histology and histomorphometry were performed at 1, 2, 4, and 6 weeks. RESULTS: PEG HD revealed the highest percentage of residual matrix at all time points starting with 47.2% (95% CI: 32.8-63.8%) at 1 week and ending with 23.4% (95% CI: 10.3-49.8%) at 6 weeks. The hydrogel with the loosest network (PEG LD/RGD) was stable the first 2 weeks and then degraded continuously with a final area of 8.3% (95% CI: 3.2-21.2%). PEG HD was the most stable and densely stained membrane, whereas PEG MD and PEG LD matrices integrated faster, but started to degrade to a higher degree between 2 and 4 weeks. PEG MD degradation was dependent on the addition of RGD and the amount of CMC. CONCLUSIONS: Chemical and/or physical modifications of PEG hydrogels influenced matrix stability. PEG MD/RGD demonstrated an optimal balance between degradation time and integration into the surrounding soft and hard tissues.