Validation of the BCIS CHIP Score in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The complex high-risk indicated percutaneous coronary intervention (CHIP) score is a tool developed using the British Cardiovascular Intervention Society (BCIS) database to define CHIP cases and predict in-hospital major adverse cardiac or cerebrovascular events (MACCE). AIM: To assess the validity of the CHIP score in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We evaluated the performance of the CHIP score on 8341 CTO PCIs from the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) performed at 44 centers between 2012 and 2023. RESULTS: In our cohort, 7.8% (n = 647) of patients had a CHIP score of 0, 50.2% (n = 4192) had a CHIP score of 1-2, 26.2% (n = 2187) had a CHIP score of 3-4, 11.7% (n = 972) had a CHIP score of 5-6, 3.3% (n = 276) had a CHIP score of 7-8, and 0.8% (n = 67) had a CHIP score of 9+. The incidence of MACCE for a CHIP score of 0 was 0.6%, reaching as high as 8.7% for a CHIP score of 9+, confirming that a higher CHIP score is associated with a higher risk of MACCE. The estimated increase in the risk of MACCE per one score unit increase was 100% (95% confidence interval [CI]: 65%-141%). The AUC of the CHIP score model for predicting MACCE in our cohort was 0.63 (95% CI: 0.58-0.67). There was a positive correlation between the CHIP score and the PROGRESS-CTO MACE score (Spearman's correlation: 0.37; 95% CI: 0.35-0.39; p < 0.001). CONCLUSIONS: The CHIP score has modest predictive capacity for MACCE in CTO PCI.

Impact of lesion length on the outcomes of chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: The impact of occlusion length on the procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 10,335 CTO PCIs at 42 US and non-US centers between 2012 and 2022. The cohort was divided into two groups based on lesion length (≥20 mm vs. <20 mm). RESULTS: Long lesions were present in 7208 (70%) patients. Comorbidities were more common in patients with long CTOs. Compared with short lesions, long lesions had higher J-CTO score (2.8 ± 1.1 vs. 1.3 ± 1; p < 0.001) and retrograde wiring was more often the initial (15.5% vs. 4.0%; p < 0.001) and successful (22.8% vs. 8.2%; p < 0.001) crossing strategy. Long lesions were more likely to require longer procedure (123 vs. 91 min; p < 0.001) and fluoroscopy (47.1 vs. 32.2 min; p < 0.001) time, larger contrast volume (218 vs. 200 mL; p < 0.001) and higher air kerma radiation dose (2.4 vs. 1.7 Gy; p < 0.001). After adjusting for potential confounders, long lesions were associated with lower technical success (odds ratio [OR]: 0.91 per 10 mm increase; 95% confidence interval [CI]: 0.88, 0.94) and higher major adverse cardiovascular events (MACE) (OR: 1.08 per 10 mm increase; 95% CI: 1.02, 1.15). CONCLUSIONS: CTO PCI of long occlusions is independently associated with lower rates of technical success and higher rates of in-hospital MACE.

Impact of preprocedural anemia on in-hospital and follow-up outcomes of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The impact of preprocedural anemia on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 8633 CTO PCIs performed at 39 US and non-US centers between 2012 and 2023. Anemia was defined as a hemoglobin level of <13 g/dL in men and <12 g/dL in women. RESULTS: Anemia was present in 1652 (19%) patients undergoing CTO PCI. Anemic patients had a higher incidence of comorbidities, such as diabetes mellitus, hypertension, dyslipidemia, heart failure, cerebrovascular disease, and peripheral arterial disease. CTOs in anemic patients were more likely to have complex angiographic characteristics, including smaller diameter, longer length, moderate to severe calcification, and moderate to severe proximal tortuosity. Anemic patients required longer procedure (119 vs. 107 min; p < 0.001) and fluoroscopy (45 vs. 40 min; p < 0.001) times but received similar contrast volumes. Technical success was similar between the two groups. In-hospital major adverse cardiac events (MACE) rates were higher in patients with anemia; however, this association was no longer significant after adjusting for confounding factors. Baseline anemia was independently associated with follow-up MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.07-2.49; p = 0.023) and all-cause mortality (adjusted HR: 3.03; 95% CI: 1.41-6.49; p = 0.004). CONCLUSIONS: Preprocedural anemia is associated with more comorbidities, higher lesion complexity, longer procedure times, and higher follow-up MACE and mortality after CTO PCI.

NHLBI-Sponsored Randomized Trial of Postconditioning During Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

RATIONALE: Postconditioning at the time of primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction may reduce infarct size and improve myocardial salvage. However, clinical trials have shown inconsistent benefit. OBJECTIVE: We performed the first National Heart, Lung, and Blood Institute-sponsored trial of postconditioning in the United States using strict enrollment criteria to optimize the early benefits of postconditioning and assess its long-term effects on left ventricular (LV) function. METHODS AND RESULTS: We randomized 122 ST-segment-elevation myocardial infarction patients to postconditioning (4, 30 seconds PTCA [percutaneous transluminal coronary angioplasty] inflations/deflations)+PCI (n=65) versus routine PCI (n=57). All subjects had an occluded major epicardial artery (thrombolysis in myocardial infarction=0) with ischemic times between 1 and 6 hours with no evidence of preinfarction angina or collateral blood flow. Cardiac magnetic resonance imaging measured at 2 days post-PCI showed no difference between the postconditioning group and control in regards to infarct size (22.5±14.5 versus 24.0±18.5 g), myocardial salvage index (30.3±15.6% versus 31.5±23.6%), or mean LV ejection fraction. Magnetic resonance imaging at 12 months showed a significant recovery of LV ejection fraction in both groups (61.0±11.4% and 61.4±9.1%; P<0.01). Subjects randomized to postconditioning experienced more favorable remodeling over 1 year (LV end-diastolic volume =157±34 to 150±38 mL) compared with the control group (157±40 to 165±45 mL; P<0.03) and reduced microvascular obstruction ( P=0.05) on baseline magnetic resonance imaging and significantly less adverse LV remodeling compared with control subjects with microvascular obstruction ( P<0.05). No significant adverse events were associated with the postconditioning protocol and all patients but one (hemorrhagic stroke) survived through 1 year of follow-up. CONCLUSIONS: We found no early benefit of postconditioning on infarct size, myocardial salvage index, and LV function compared with routine PCI. However, postconditioning was associated with improved LV remodeling at 1 year of follow-up, especially in subjects with microvascular obstruction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01324453.

Quantifying cellular protrusion in alginate capsules with covalently crosslinked shells.

This work describes viability and distribution of INS-1E beta cells in shell-crosslinked alginate capsules, focussing on cells located near the capsule surface. Capsules were formed by air-shearing alginate suspensions of INS-1E cells into a gelling bath, and coating with poly-l-lysine (PLL) and 50% hydrolysed poly(methylvinylether-alt-maleic anhydride) to form crosslinked networks reinforcing the capsule surfaces. The percentage of cells at the capsule surface were determined using 2D and 3D confocal colocalization mapping. Encapsulated INS-1E cells showed high cell viability and progressive cell clustering out to six weeks. About 30% of cells were initially colocated with the 20 micrometer thick alginate-PLL-PMM50 shell, with 7% of cells protruded at the capsule surfaces, both reflecting random cell distributions. Protruding cells may cause cell-based immune responses, weaken capsules, and potentially result in cell escape from the capsules. The data shown indicate that reinforcing capsules with crosslinked shells may assist in preventing cell exposure and escape.

Cross-Linked Hydrogels Formed through Diels-Alder Coupling of Furan- and Maleimide-Modified Poly(methyl vinyl ether-alt-maleic acid).

The Diels-Alder [4 + 2] cycloaddition between furan- and maleimide-functional polyanions was used to form cross-linked synthetic polymer hydrogels. Poly(methyl vinyl ether-alt-maleic anhydride) was reacted with furfurylamine or N-(2-aminoethyl)maleimide in acetonitrile to form pairs of furan- and maleimide-functionalized poly(methyl vinyl ether-alt-maleic acid)s. Mixtures of these mutually reactive polyanions in water gelled within 15 min to 18 h, depending on degree of functionalization and polymer concentrations. Solution and magic-angle spinning (1)H NMR were used to confirm the formation of the Diels-Alder adduct, to analyze competing hydrolytic side reactions, and demonstrate postgelation functionalization. The effect of the degree of furan and maleimide functionalization, polymer concentration, pH, and calcium ion concentration, on gelation time, gel mechanical properties, and equilibrium swelling, are described. Release of dextran as a model drug was studied using fluorescence spectroscopy, as a function of gel composition and calcium treatment.

Tunable hydrogel thin films from reactive synthetic polymers as potential two-dimensional cell scaffolds.

This article describes the formation of cross-linked 10-200-nm-thick polymer hydrogel films by alternating the spin-coating of two mutually reactive polymers from organic solutions, followed by hydrolysis of the resulting multilayer film in aqueous buffer. Poly(methyl vinyl ether-alt-maleic anhydride) (PMM) was deposited from acetonitrile solution, and poly(N-3-aminopropylmethacrylamide-co-N-2-hydroxypropylmethacrylamide) (PAPMx, where x corresponds to the 3-aminopropylmethacrylamide content ranging from 10 to 100%) was deposited from methanol. Multilayer films were formed in up to 20 deposition cycles. The films cross-linked during formation by reaction between the amine groups of PAPMx and the anhydride groups of PMM. The resulting multilayer films were covalently postfunctionalized by exposure to fluoresceinamine, decylamine, d-glucamine, or fluorescently labeled PAPMx solutions prior to the hydrolysis of residual anhydride in aqueous PBS buffer. This allowed tuning the hydrophobicity of the film to give static water contact angles ranging from about 5 to 90°. Increasing the APM content in PAPMx from 10 to 100% led to apparent Young's moduli from 300 to 700 kPa while retaining sufficient anhydride groups to allow postfunctionalization of the films. This allowed the resulting (PMM/PAPMx) multilayer films to be turned into adhesion-promoting or antifouling surfaces for C2C12 mouse myoblasts and MCF 10A premalignant human mammary epithelial cells.

Decreased blood flow in the throwing arm of professional baseball pitchers.

BACKGROUND: As a consequence of the repetitive forces placed on the throwing arm of a baseball player, various bony, capsuloligamentous, and muscular adaptations occur and have been identified. However, no research has identified whether adaptations also exist in the vasculature of the upper extremity in the competitive baseball player. METHODS: Fifty-one professional baseball pitchers and 34 position players participated. Diagnostic ultrasound was used to measure bilateral blood flow of the brachial artery. These measurements were taken with the participant standing with the test arm resting at the participant's side and again with the test arm in a provocative shoulder position. RESULTS: The throwing arm of the pitchers had significantly less blood flow volume when in the provocative shoulder position compared with their nonthrowing arm (P = .01). Pitchers did not have any bilateral difference while in the resting position (P = .19). There were no bilateral differences among the position players while in the resting (P = .64) or provocative positions (P = .63). Pitchers had significantly less blood flow of the throwing shoulder while in the provocative position compared with position players (P = .02). There were no other between-group differences. CONCLUSIONS: While in a provocative shoulder position, pitchers have significantly less blood flow in their throwing arm compared with their nonthrowing arm and with the throwing arm of position players. These results provide a descriptive profile of blood flow volume among baseball players, which may be used in the evaluation and treatment of such athletes with vascular disorders.

Incidence, treatment and outcomes of coronary artery dissection during percutaneous coronary intervention.

BACKGROUND: Coronary artery dissection is a feared and potentially life-threatening complication of percutaneous coronary intervention (PCI). METHODS: We examined the clinical, angiographic, and procedural characteristics, and outcomes of coronary dissection at a tertiary care institution. RESULTS: Between 2014 and 2019, unplanned coronary dissection occurred in 141 of 10,278 PCIs (1.4%). Median patient age was 68 (60, 78) years, 68% were men, and 83% had hypertension. The prevalence of diabetes (29%), and prior PCI (37%) was high. Most target vessels were significantly diseased: 48% had moderate/severe tortuosity and 62% had moderate/severe calcification. The most common cause of dissection was guidewire advancement (30%), followed by stenting (22%), balloon angioplasty (20%), and guide-catheter engagement (18%). TIMI flow was 0 in 33% and 1-2 in 41% of cases. Intravascular imaging was used in 17% of the cases. Stenting was used to treat the dissection in 73% of patients. There was no consequence of dissection in 43% of patients. Technical and procedural success was 65% and 55%, respectively. In-hospital major adverse cardiovascular events occurred in 23% of patients: 13 (9%) had an acute myocardial infarction (MI), 3 (2%) had emergency coronary artery bypass graft surgery, and 10 (7%) died. During a mean follow up of 1612 days, 28 (20%) patients died, and the rate of target lesion revascularization was 11.3% (n=16). CONCLUSION: Coronary artery dissection is an infrequent complication of PCI, but is associated with adverse clinical outcomes, such as death and acute MI.

Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention After a Previous Failed Attempt.

The impact of a previous failure on procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We examined the clinical and angiographic characteristics and procedural outcomes of 9,393 patients who underwent 9,560 CTO PCIs at 42 United States and non-United States centers between 2012 and 2022. A total of 1,904 CTO lesions (20%) had a previous failed PCI attempt. Patients who underwent reattempt CTO PCI were more likely to have a family history of coronary artery disease (37% vs 31%, p <0.001) and dyslipidemia (87.9% vs 84.3%, p <0.001) but were less likely to have heart failure (25.1% vs 29.5%; p <0.001) and cerebrovascular disease (8.7% vs 10.4%, p = 0.04). Patients with previous failure had a higher Japanese CTO (3.33 ± 1.16 vs 2.12 ± 1.19, p <0.001) score and required longer procedure (120 vs 111 minutes, p <0.001) and fluoroscopy (46.9 vs 40.4 minutes, p <0.001) times and higher air kerma radiation dose (2.3 vs 2.1 gray, p = 0.013). Technical success rates (84.3% vs 86.5%, p = 0.011) were lower in patients with a previous failure compared with patients who underwent first-attempt CTO PCI with no significant difference in in-hospital major adverse cardiac events. After adjusting for potential confounders, a previous failure was not associated with technical failure. Operators performing >30 CTO PCIs annually were more likely to achieve technical success in patients with previous failure. In conclusion, a previous failed CTO PCI attempt was associated with higher lesion complexity, longer procedure time, and lower technical success; however, the association with lower technical success did not remain significant in multivariable analysis.

Case series analysis of eight underground tunnellers with chronic silicosis in Queensland.

Within Australia, chronic silicosis has been long thought of as being a well-controlled occupational lung disease. While recent cases of acute silicosis in artificial stone benchtop cutters have emerged, chronic silicosis within the general workforce population has not been recorded. Our case series describes the re-emergence of chronic silicosis amongst workers within the tunnelling industry representing the potential for a more widespread insidious occupational lung disease. While undertaking pre-employment medicals, eight tunnellers have been diagnosed with chronic silicosis. These eight tunnellers had a minimum of 10 years of cumulative dust exposure prior to diagnosis. Diagnosis was made by radiological evaluation of chest X-rays and computerized tomography scans by International Labour Organization B Readers. The re-emergence of chronic pneumoconiosis as illustrated by this case series suggests the presence of undiagnosed occupational lung disease with far reaching implications for workers, employers, compensation systems, and the public healthcare sectors.

Cross-linked microcapsules formed from self-deactivating reactive polyelectrolytes.

Poly(methyl vinyl ether-alt-maleic anhydride) (PMM(0)) was partially hydrolyzed in a 9/1 acetonitrile-d(3)/D(2)O mixture and then diluted with an aqueous buffer and coated onto poly-L-lysine (PLL)-coated calcium alginate capsules. The resulting 50% hydrolyzed polymer (PMM(50)) is bound to the surface-immobilized PLL through both electrostatic and covalent interactions, resulting in a shell-cross-linked hydrogel capsule that is resistant to chemical challenges. Further hydrolysis of PMM(50) in aqueous buffer was monitored by potentiometry and was found to proceed with a half-life time of about 2.5 min at 20 degrees C such that residual anhydride groups not consumed by cross-linking with PLL would be deactivated by hydrolysis within several minutes of shell formation, removing potential sites for undesired protein binding. Initial protein-binding tests involving incubation of the capsules in bovine serum albumin solutions for 24 h showed no indication of protein binding. The effects of coating temperature, PLL concentration and molecular weight, PMM(50) molecular weight, and multiple PLL-PMM(50) coatings on shell morphology and behavior were studied using confocal fluorescence microscopy as well as chemical challenges involving sodium citrate and sodium hydroxide. The resilience of the cross-linked shell improved with increasing concentrations of PLL and decreasing molecular weight of PMM(50), both of which resulted in more polyelectrolyte being bound to the capsule. The permeability of these covalently cross-linked capsules was studied using fluorescently labeled dextrans and was found to be comparable to standard calcium alginate-PLL-alginate (APA) capsules.

Clinical Characteristics and Outcomes of STEMI Patients With Cardiogenic Shock and Cardiac Arrest.

OBJECTIVES: This study sought to compare the clinical characteristics and long-term outcomes of patients with ST-segment elevation myocardial infarction (STEMI) with and without cardiogenic shock (CS) or cardiac arrest (CA) before percutaneous coronary intervention (PCI). BACKGROUND: Patients with STEMI complicated by CS or CA are underrepresented in STEMI registries. METHODS: Consecutive patients with STEMI or new left bundle branch block within 24 h of symptom onset were included in a regional STEMI program comprising a PCI center (Minneapolis Heart Institute at Abbott Northwestern Hospital), 11 hospitals <60 miles from PCI center (zone 1), and 19 hospitals 60 to 210 miles from PCI center (zone 2). No patients were excluded. Patients were stratified based on the presence (+) or absence (-) of CS or CA before PCI. Patients with CA were further classified based on initial rhythm. Primary outcomes were in-hospital and 5-year mortality. RESULTS: Between March 2003 and December 2014, 4,511 STEMI patients were included in the regional program, including 398 (9%) with CS and 499 (11%) with CA. Hospital mortality was: CS+ and CA+, 44%; CS+ and CA-, 23%; CS- and CA+, 19%; and CS- and CA-, 2% (p < 0.001). The 5-year survival probability for CS+ and CA+ patients was 0.69 (95% confidence interval: 0.61 to 0.76) and 0.89 (95% confidence interval: 0.84 to 0.93), respectively (p < 0.01). Compared with patients with shockable rhythms, CA patients with nonshockable rhythms had significantly lower odds of survival at hospital discharge and at 5 years (both p < 0.001). CONCLUSIONS: The combination of CS and CA significantly increases short-term mortality in patients with STEMI. After 5 years of follow-up, CS patients remained at high risk of fatal events, whereas the prognosis of CA patients was determined by initial rhythm at presentation.

Impact of Successful Chronic Total Occlusion Percutaneous Coronary Interventions on Subsequent Clinical Outcomes.

BACKGROUND: The impact of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on angina and subsequent incidence of major adverse cardiovascular event (MACE) rate remains controversial. METHODS: We compared patient- reported angina change and the incidence of MACE (defined as death, myocardial infarction [MI], target-vessel revascularization) between successful vs failed CTO-PCI in 1612 patients participating in a large, multicenter registry. RESULTS: CTO-PCI was successful in 1387 patients (86%). Compared with failed CTO-PCI, successful CTO-PCI patients were less likely to have history of heart failure (33% vs 41%; P=.02), prior MI (49% vs 62%; P<.01), or prior coronary revascularization (63% vs 71% [P=.03] for PCI and 30% vs 40% [P<.01] for coronary artery bypass graft surgery). Patients in the successful CTO-PCI group had lower J-CTO scores (2.4 ± 1.3 vs 3.1 ± 1.1; P<.01) and lower PROGRESS-CTO Complications scores (1.1 ± 1.0 vs 1.6 ± 1.0; P<.01). After a mean follow-up of 181 ± 153 days, patients with successful PCI were more likely to have angina improvement (83% vs 38%; P<.01) and had lower incidence of 1-year MACE (8% vs 15%; P<.01), death (3% vs 7%; P<.01), and MI (2% vs 4%; P=.02). On multivariable analysis, however, CTO-PCI success was not independently associated with MACE. CONCLUSION: Compared with failed CTO-PCI, successful CTO-PCI is associated with better angina improvement and lower incidence of MACE (on univariable analysis) during follow-up.

Core-cross-linked alginate microcapsules for cell encapsulation.

Self-cross-linkable polyelectrolyte pairs comprised of poly(methacrylic acid, sodium salt-co-2-[methacryloyloxy]ethyl acetoacetate) (70:30 mol ratio, A70) and poly-L-lysine are incorporated into CaAlg beads to form either a covalently cross-linked shell or a core-cross-linked bead. In both cases the reactive polyanion is added to a solution of sodium alginate that may contain live cells and dropped into a calcium chloride gelling bath. Subsequent exposure to poly-L-lysine (15-30 kDa) leads to formation of a cross-linked shell, while exposure to lower molecular weight poly-L-lysine (4-15 kDa) leads to formation of an interpenetrating matrix of covalently cross-linked synthetic polymer within the CaAlg template. The resulting spherical composites are resistant to chemical and mechanical stress yet remain cyto-compatible. This approach to cell-encapsulation may be useful for cell immuno-isolation in therapeutic cell transplants.

Australian military primary care practitioners do not believe clinical practice guidelines are needed for postdeployment medically unexplained symptoms.

In Australia, little research has been undertaken on the development of clinical practice guidelines (CPGs) to assist with the impact of postdeployment ill-health including medically unexplained symptoms (MUS) and it has been unclear whether such a development is desired by Australian primary care practitioners. In response an empirical investigation into the perceptions and experiences of 24 medical officers from the Australian military with regard to postdeployment ill-health, medically unexplained symptoms, and the potential development of CPGs in this area was undertaken. The analysis suggests that although MUS are accepted as common in general practice they are not perceived by practitioners to be as prevalent in the Australian Defense Forces. Although the medical officers do not perceive clinical practice guidelines as the best tool for managing MUS, there was interest in the development of practical tools to assist in the diagnosis of medically unexplained symptoms. The response by practitioners is of critical importance for the potential implementation of clinical practice guidelines in this area.

Self-cross-linking polyelectrolyte complexes for therapeutic cell encapsulation.

Self-cross-linking polyelectrolytes are used to strengthen the surface of calcium alginate beads for cell encapsulation. Poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), containing 30 mol % 2-aminoethyl methacrylate, and poly(sodium methacrylate), containing 30 mol % 2-(methacryloyloxy)ethyl acetoacetate, were prepared by radical polymerization. Sequential deposition of these polyelectrolytes on calcium alginate films or beads led to a shell consisting of a covalently cross-linked polyelectrolyte complex that resisted osmotic pressure changes as well as challenges with citrate and high ionic strength. Confocal laser fluorescence microscopy revealed that both polyelectrolytes were concentrated in the outer 7-25 microm of the calcium alginate beads. The thickness of this cross-linked shell increased with exposure time. GPC studies of solutions permeating through analogous flat model membranes showed molecular weight cut-offs between 150 and 200 kg/mol for poly(ethylene glycol), suitable for cell encapsulation. C 2C 12 mouse cells were shown to be viable within calcium alginate capsules coated with the new polyelectrolytes, even though some of the capsules showed fibroid overcoats when implanted in mice due to an immune response.

Synthetic polycations with controlled charge density and molecular weight as building blocks for biomaterials.

A series of polycations prepared by RAFT copolymerization of N-(3-aminopropyl)methacrylamide hydrochloride (APM) and N-(2-hydroxypropyl)methacrylamide, with molecular weights of 15 and 40 kDa, and APM content of 10-75 mol%, were tested as building blocks for electrostatically assembled hydrogels such as those used for cell encapsulation. Complexation and distribution of these copolymers within anionic calcium alginate gels, as well as cytotoxicity, cell attachment, and cell proliferation on surfaces grafted with the copolymers were found to depend on composition and molecular weight. Copolymers with lower cationic charge density and lower molecular weight showed less cytotoxicity and cell adhesion, and were more mobile within alginate gels. These findings aid in designing improved polyelectrolyte complexes for use as biomaterials.

Systematic study of alginate-based microcapsules by micropipette aspiration and confocal fluorescence microscopy.

Micropipette aspiration and confocal fluorescence microscopy were used to study the structure and mechanical properties of calcium alginate hydrogel beads (A beads), as well as A beads that were additionally coated with poly-L-lysine (P) and sodium alginate (A) to form, respectively, AP and APA hydrogels. A beads were found to continue curing for up to 500 h during storage in saline, due to residual calcium chloride carried over from the gelling bath. In subsequent saline washes, micropipette aspiration proved to be a sensitive indicator of gel weakening and calcium loss. Aspiration tests were used to compare capsule stiffness before and after citrate extraction of calcium. They showed that the initial gel strength is largely due to the calcium alginate gel cores, while the long term strength is solely due to the poly-L-lysine-alginate polyelectrolyte complex (PEC) shells. Confocal fluorescence microscopy showed that calcium chloride exposure after PLL deposition led to PLL redistribution into the hydrogel bead, resulting in thicker but more diffuse and weaker PEC shells. Adding a final alginate coating to form APA capsules did not significantly change the PEC membrane thickness and stiffness, but did speed the loss of calcium from the bead core.

Poly(methyl vinyl ether-alt-maleic acid) polymers for cell encapsulation.

Polyanions based on poly(methyl vinyl ether-alt-maleic acid) were investigated as materials for cell encapsulation. These water-soluble polyanions having molecular masses ranging from 20 to 1980 kDa were prepared by functionalization of poly(methyl vinyl ether-alt-maleic anhydride) with 5-aminofluorescein and/or α-methoxy-ω-amino-poly(ethylene glycol), followed by base hydrolysis of the residual anhydride groups to form the corresponding poly(methyl vinyl ether-alt-sodium maleate). Their potential to replace alginate both in the core and, in particular, the outer shell of calcium alginate-poly(L-lysine)-alginate (APA) capsules was determined using confocal fluorescence microscopy, osmotic pressure tests, permeability studies, protein binding and cell viability assays. These polymers were shown to be able to replace the outer layer of alginate, forming more resilient capsule shells. The resulting capsules showed similar permeability and resistance to bovine serum albumin binding, as well as superior viability for encapsulated cells, when compared to standard APA capsules. In addition, these polymers showed promise for use as functional additives to the capsule cores.