Multimorbidity and patterns of chronic conditions in a primary care population in Switzerland: a cross-sectional study.

OBJECTIVE: To characterise in details a random sample of multimorbid patients in Switzerland and to evaluate the clustering of chronic conditions in that sample. METHODS: 100 general practitioners (GPs) each enrolled 10 randomly selected multimorbid patients aged ≥18 years old and suffering from at least three chronic conditions. The prevalence of 75 separate chronic conditions from the International Classification of Primary Care-2 (ICPC-2) was evaluated in these patients. Clusters of chronic conditions were studied in parallel. RESULTS: The final database included 888 patients. Mean (SD) patient age was 73.0 (12.0) years old. They suffered from 5.5 (2.2) chronic conditions and were prescribed 7.7 (3.5) drugs; 25.7% suffered from depression. Psychological conditions were more prevalent among younger individuals (≤66 years old). Cluster analysis of chronic conditions with a prevalence ≥5% in the sample revealed four main groups of conditions: (1) cardiovascular risk factors and conditions, (2) general age-related and metabolic conditions, (3) tobacco and alcohol dependencies, and (4) pain, musculoskeletal and psychological conditions. CONCLUSION: Given the emerging epidemic of multimorbidity in industrialised countries, accurately depicting the multiple expressions of multimorbidity in family practices' patients is a high priority. Indeed, even in a setting where patients have direct access to medical specialists, GPs nevertheless retain a key role as coordinators and often as the sole medical reference for multimorbid patients.

How the probability of presentation to a primary care clinician correlates with cancer survival rates: a European survey using vignettes.

OBJECTIVE: European cancer survival rates vary widely. System factors, including whether or not primary care physicians (PCPs) are gatekeepers, may account for some of these differences. This study explores where patients who may have cancer are likely to present for medical care in different European countries, and how probability of presentation to a primary care clinician correlates with cancer survival rates. DESIGN: Seventy-eight PCPs in a range of European countries assessed four vignettes representing patients who might have cancer, and consensus groups agreed how likely those patients were to present to different clinicians in their own countries. These data were compared with national cancer survival rates. SETTING: A total of 14 countries. SUBJECTS: Consensus groups of PCPs. MAIN OUTCOME MEASURES: Probability of initial presentation to a PCP for four clinical vignettes. RESULTS: There was no significant correlation between overall national 1-year relative cancer survival rates and the probability of initial presentation to a PCP (r = -0.16, 95% CI -0.39 to 0.08). Within that there was large variation depending on the type of cancer, with a significantly poorer lung cancer survival in countries where patients were more likely to initially consult a PCP (lung r = -0.57, 95% CI -0.83 to -0.12; ovary: r = -0.13, 95% CI -0.57 to 0.38; breast r = 0.14, 95% CI -0.36 to 0.58; bowel: r = 0.20, 95% CI -0.31 to 0.62). CONCLUSIONS: There were wide variations in the degree of gatekeeping between countries, with no simple binary model as to whether or not a country has a "PCP-as-gatekeeper" system. While there was case-by-case variation, there was no overall evidence of a link between a higher probability of initial consultation with a PCP and poorer cancer survival. KEY POINTS European cancer survival rates vary widely, and health system factors may account for some of these differences. The data from 14 European countries show a wide variation in the probability of initial presentation to a PCP. The degree to which PCPs act as gatekeepers varies considerably from country to country. There is no overall evidence of a link between a higher probability of initial presentation to a PCP and poorer cancer survival.

Engineered acellular collagen scaffold for endogenous cell guidance, a novel approach in urethral regeneration.

UNLABELLED: The treatment of congenital malformations or injuries of the urethra using existing autologous tissues can be associated with post-operative complications. Using rat-tail collagen, we have engineered an acellular high-density collagen tube. These tubes were made of 2 layers and they could sustain greater burst pressures than the monolayered tubes. Although it remains a weak material this 2 layered tube could be sutured to the native urethra. In 20 male New Zealand white rabbits, 2cm long grafts were sutured in place after subtotal excision of the urethra. This long-term study was performed in Lausanne (Switzerland) and in Kuala Lumpur (Malaysia). No catheter was placed post-operatively. All rabbits survived the surgical implantation. The animals were evaluated at 1, 3, 6, and 9months by contrast voiding cysto-urethrography, histological examination and immunohistochemistry. Spontaneous re-population of urothelial and smooth muscle cells on all grafts was demonstrated. Cellular organization increased with time, however, 20% of both fistula and stenosis could be observed post-operatively. This off-the shelf scaffold with a promising urethral regeneration has a potential for clinical application. STATEMENT OF SIGNIFICANCE: In this study we have tissue engineered a novel cell free tubular collagen based scaffold and used it as a urethral graft in a rabbit model. The novelty of our technique is that the tube can be sutured. Testing showed better burst pressures and the grafts could then be successfully implanted after a urethral excision. This long term study demonstrated excellent biocompatibility of the 2cm graft and gradual regeneration with time, challenging the current literature. Finally, the main impact is that we describe an off-the-shelf and cost-effective product with comparable surgical outcome to the cellular grafts.

Tubular Compressed Collagen Scaffolds for Ureteral Tissue Engineering in a Flow Bioreactor System.

Ureteral replacement by tissue engineering might become necessary following tissue loss after excessive ureteral trauma, after retroperitoneal cancer, or even after failed reconstructive surgery. This need has driven innovation in the design of novel scaffolds and specific cell culture techniques for urinary tract reconstruction. In this study, compressed tubular collagen scaffolds were evaluated, addressing the physical and biological characterization of acellular and cellular collagen tubes in a new flow bioreactor system, imitating the physiological pressure, peristalsis, and flow conditions of the human ureter. Collagen tubes, containing primary human smooth muscle and urothelial cells, were evaluated regarding their change in gene and protein expression under dynamic culture conditions. A maximum intraluminal pressure of 22.43 ± 0.2 cm H2O was observed in acellular tubes, resulting in a mean wall shear stress of 4 dynes/cm(2) in the tubular constructs. Dynamic conditions directed the differentiation of both cell types into their mature forms. This was confirmed by their gene expression of smooth muscle alpha-actin, smoothelin, collagen type I and III, elastin, laminin type 1 and 5, cytokeratin 8, and uroplakin 2. In addition, smooth muscle cell alignment predominantly perpendicular to the flow direction was observed, comparable to the cell orientation in native ureteral tissue. These results revealed that coculturing human smooth muscle and urothelial cells in compressed collagen tubes under human ureteral flow-mimicking conditions could lead to cell-engineered biomaterials that might ultimately be translated into clinical applications.

Is there a need for smooth muscle cell transplantation in urethral reconstruction?

BACKGROUND: Hypospadias and urethral strictures are conditions requiring additional tissue for reconstruction. Due to a limited source of tissue, autologous skin and oral mucosa are frequently used. However, long-term follow-up studies demonstrated significant complications and diminished quality of life. Recently, a variety of tubular biodegradable biomaterials have been used. Cell seeding seems to be important to improve the host acceptance and neovascularization. OBJECTIVE: To compare in vivo performance of smooth muscle cell (SMC)-seeded and unseeded tubular collagen-based scaffolds in a rabbit urethral reconstruction model. MATERIALS AND METHODS: Sixteen New Zealand rabbits underwent an open-bladder biopsy for SMC harvesting. The SMCs were cultured for 3 weeks and labeled with ethynyldeoxyuridine (EdU). A 1-cm-length tubular collagen-based 0.5 wt% scaffold was seeded and cultured with SMCs and implantation in a rabbit model. Eight rabbits received SMC-seeded scaffolds for a 1-cm-length circumferential urethral repair, situated 1.5 cm from the meatus. After 1 and 3 months, four rabbits underwent a urethrography and were sacrificed. The penises underwent hematoxylin and eosin, immunohistochemistry, and EdU fluorescence staining. In the control group eight rabbits received acellular scaffolds. RESULTS: The SMC-seeded group presented one stricture at 1 month and one fistula at 3 months. Three strictures were present in the unseeded group at 1 month and one at 3 months. In the seeded group, more SMC expression and neovascularization was observed, and less mononuclear and giant cells could be found. All scaffolds showed luminal urothelial cell revetment. The detection of EdU-labeled SMCs revealed SMC transplantation survival. CONCLUSION: SMC-seeded tubular collagen scaffolds improved urethral regeneration in this rabbit model. Such constructs may be valuable for repair of severe urethral diseases.

In-vivo performance of high-density collagen gel tubes for urethral regeneration in a rabbit model.

Congenital malformations or injuries of the urethra can be treated using existing autologous tissue, but these procedures are sometimes associated with severe complications. Therefore, tissue engineering may be advantageous for generating urethral grafts. We evaluated engineered high-density collagen gel tubes as urethral grafts in 16 male New Zealand white rabbits. The constructs were either acellular or seeded with autologous smooth muscle cells, isolated from an open bladder biopsy. After the formation of a urethral defect by excision, the tissue-engineered grafts were interposed between the remaining urethral ends. No catheter was placed postoperatively. The animals were evaluated at 1 or 3 months by contrast urethrography and histological examination. Comparing the graft caliber to the control urethra at 3 months, a larger caliber was found in the cell-seeded grafts (96.6% of the normal caliber) than in the acellular grafts (42.3%). Histology of acellular and cell-seeded grafts did not show any sign of inflammation, and spontaneous regrowth of urothelium could be demonstrated in all grafts. Urethral fistulae, sometimes associated with stenosis, were observed, which might be prevented by urethral catheter application. High-density collagen gel tubes may be clinically useful as an effective treatment of congenital and acquired urethral pathologies.

Urodynamic score in children with lipomyelomeningocele: a prospective study.

PURPOSE: We assessed the correlation between urodynamic score and presence of symptoms in children with lipomyelomeningocele, and the usefulness of this measure in monitoring these children. MATERIALS AND METHODS: We prospectively evaluated 29 patients 1 month to 13 years old (mean 1.9 years) with lipomyelomeningocele from 1995 to 2010. A 4-parameter urodynamic score ranging from 0 to 17 was assigned to each patient at diagnosis and followup. Indications for surgery were presence of symptoms and signs or abnormal urodynamic score. Children were divided into 2 groups, symptomatic and asymptomatic. The latter group was further divided into operated and conservatively managed cases. Average followup was 6.7 years (range 2 to 16). RESULTS: The symptomatic group contained 11 children (38%) operated on at a mean age of 2.9 years. Mean followup was 6.7 years (range 2 to 12). All patients presented with an abnormal urodynamic score. Postoperative urodynamic score improved in 6 patients (55%), remained abnormal in 4 (36%) and deteriorated in 1 (9%). The asymptomatic group contained 18 patients, of whom 7 (39%) were operated on at a mean age of 1.4 years. Mean followup was 10 years (range 3 to 16). Postoperative score improved in 6 patients (86%) and remained unchanged in 1 (14%). A total of 11 cases (61%) were managed conservatively, with a mean followup 4.3 years (range 2 to 7). Of these patients 3 (27%) presented with late urodynamic score deterioration at 3, 5 and 6 years of followup while remaining asymptomatic. CONCLUSIONS: Urodynamic score is a useful tool in monitoring children with lipomyelomeningocele because it has a good correlation with the presence of symptoms.

Identification of prenyl ethyl ether as a source of metallic, solvent-like off-flavor in hazelnut.

In a large batch of ground hazelnuts, a metallic, solvent-like off-note was detected. In this investigation, the volatiles from the batch showing off-notes were compared to a batch without off-notes. On the basis of gas chromatography (GC) sniffing and instrumental analysis, a terpenoid compound, prenyl ethyl ether, was identified as a key contributor to the off-note. The compound was quantified, and its contribution to the metallic, solvent-like off-flavor was confirmed by spiking experiments and sensory evaluation. Analytical and sensory experiments found that the off-note was still present in hazelnut cakes. Fat oxidation did not contribute to the off-flavor. Analysis of market products demonstrated the correlation between the identified terpenoid and the off-flavor. It is assumed that fungi are involved in off-flavor formation.

In vivo study of an injectable poly(acrylonitrile)-based hydrogel paste as a bulking agent for the treatment of urinary incontinence.

Urinary incontinence can be treated by endoscopic injection of bulking agents, however, no optimal therapeutic effect has been achieved upon this treatment yet. In the present study, the development of a injectable poly(acrylonitrile) hydrogel paste is described, and its efficacy and histological behavior, once injected into the submucosal space of the minipig bladder, are evaluated. A device was developed to mix poly(acrylonitrile) hydrogel powder with glycerin, used as carrier, prior to injection into the submucosal space of the bladder. Several paste deposits, depending on the size of the bladder, were injected per animal. The implants were harvested at days 7, 14, 21, 28, 84 and 168 and analyzed morphologically and by histology. The persistence of the implants was demonstrated. However, at later time points the implants were split up and surrounded by granulomatous tissue, which was gradually replaced by histiocytes and adipocytes. Transitory focal urothelial metaplasia was observed only at day 7 and moderate foreign body reaction was detected predominantly between the second and fifth week. This study demonstrated the feasibility to develop an injectable paste of poly(acrylonitrile) hydrogel thought to provide the expected bulking effect, necessary for the treatment of urinary incontinence.

Management of cryptorchidism in children: guidelines.

QUESTION: To develop clinical guidelines for the management of cryptorchidism in pre-pubertal boys, from early diagnosis through therapy to long-term follow-up and prognosis. METHOD: Systematic review of articles from the medical literature, referenced since 1966, using validated search strategies through the following databases: Medline, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, EMBASE, DARE, ACP Journal Club, National Guidelines Clearinghouse, Guidelines International Network. Relevant articles published after 1988 were taken as the basis for the statements. Each statement was graded on the basis of the study design and on its methodological quality (GRADE approach). A multidisciplinary panel of local experts discussed and evaluated each statement on the strength of this evidence. RESULTS: 28 statements based on the best available evidence were drafted. The experts agreed with all but two statements, which were rated uncertain. CONCLUSIONS: Cryptorchidism is best diagnosed clinically, and treated by surgical orchiopexy at age 6-12 months, without a routine biopsy. If no testis is palpable, or if other signs of hypovirilisation such as hypospadias are present, the chromosomal sex and hormonal status must be assessed. Laparoscopy is the best way of diagnosing and managing intra-abdominal testes.

The effect of enzymatically degradable poly(ethylene glycol) hydrogels on smooth muscle cell phenotype.

The formation of scar tissue due to dedifferentiation of smooth muscle cells (SMCs) is one of the major issues faced when engineering bladder tissue. Furthermore, cell sources for regenerating the SMC layer are also limiting. Here we explore if human mesenchymal stem cells (MCSs), cultured in enzymatically degradable poly(ethylene glycol) (PEG) hydrogel scaffolds can be differentiated into SMC-like cells. We explored the degree to which a less synthetic SMC phenotype can be achieved when primary human SMCs are cultured within these scaffolds, It was observed that when both MSCs and SMCs are cultured in the PEG hydrogel scaffolds, but not on traditional tissue culture plastic, they up-regulate markers associated with the less synthetic SMC phenotype, decreased expression of alpha(5) integrin and THY-1, and increased expression of alpha-smooth muscle actin (alphaSMA) and myosin. Furthermore, we show that MSCs and SMCs cultured in the PEG hydrogels are able to proliferate and express matrix metalloproteinases for up to 21d in culture, the duration of the study. This study addresses the importance of the cellular microenvironment on cell fate, and proposes synthetic instructive biomaterials as a means to direct cell differentiation and circumvent scar tissue formation during bladder reconstruction.

Endoscopic and surgical treatment of vesico-ureteral reflux in children. Comparative long-term follow-up.

PRINCIPLES: This retrospective study analyzes the long-term results of endoscopic and surgical treatment of vesico-ureteral reflux in children. METHODS: A cohort of 130 patients, 67 girls and 63 boys with a mean age of 30 months were treated either by endoscopic subureteral collagen injection (SCIN) in 92 and by Cohen reimplantation surgery in 123 refluxing ureteral units. Mean follow-up was 4.2 years varying from 1 to 8.7 years. Reflux recurrence, urinary tract infection (UTI) and renal function were evaluated. RESULTS: After SCIN reflux was absent in 64% at 6 months. 20% of the initially 92 refluxing ureters were injected twice. After one or two injections reflux was absent in 71%. In 21% recurrent reflux was of grade I or II, not requiring further treatment. UTI was observed in 27%. After Cohen ureteral reimplantation reflux was absent in 96% at 6 months. UTI was observed in 23%. Renal function at diagnosis and follow-up was compared in children with bilateral grade III reflux only. In patients treated with SCIN it was normal in 77% preoperatively and in 90% at follow-up. In patients treated by open surgery it was normal in 47% preoperatively and in 76% at follow-up. CONCLUSION: For high-grade vesico-ureteral reflux re-implantation surgery remains the gold standard. SCIN is indicated for low and medium grade reflux. Recurrent bacteriuria was observed more often after SCIN and pyelonephritis more often after open surgery. The renal function seems to be preserved with both techniques.

A lower fistula rate in hypospadias surgery.

OBJECTIVE: To determine whether specific steps taken after a critical quality control of our results in hypospadias surgery lead to a decrease in fistula rate. PATIENTS AND METHODS: Retrospective review of prospectively collected data. Between 1994 and 2001, our series of 85 tubularized plate urethroplasties (modified Duplay or Duplay-Snodgrass procedure) had a fistula rate of 25.9%. In 2001, we modified our approach by systematically padding the urethral suture with a layer of vascularized subcutaneous preputial tissue, as described by Snodgrass. Scrotal hypospadias were excluded. Surgical outcome was assessed at 1 and 12 months. In both groups, all repairs were performed by or under direct supervision of the senior author (BJM). RESULTS: After 2001, 57 hypospadias repairs were performed in 57 patients aged 8 months to 14 years (median 1.4 years). Fistula occurred in two cases, one of which closed spontaneously within 6 months. Our fistula rate had dropped to 3.5%, with a minimum follow up of 12 months. CONCLUSION: Covering the urethral suture with a padding flap of vascularized preputial tissue helps avoid fistula formation. Technique modification after critical appraisal of our own series led to a much better outcome in this demanding surgery.

Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host.

Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-beta (Abeta)-containing brain extracts from humans with Alzheimer's disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by Abeta immunodepletion, protein denaturation, or by Abeta immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains.

Neuropeptide alterations in the hippocampal formation and cortex of transgenic mice overexpressing beta-amyloid precursor protein (APP) with the Swedish double mutation (APP23).

The role of neuropeptides and the significance of peptidergic mechanisms in neurodegenerative diseases are still unclear. In the periphery, nerve injury results in dramatic changes in the expression of neuropeptides. An important question regards to what extent similar changes occur, and similar mechanisms operate, after lesions and/or degeneration in the brain. The purpose of this work is, therefore, to study neuropeptides with regard to their presence and distribution in the APP23 mouse (HuAPP(751) K670M/N671L under the murine Thy-1 promoter), a model for Alzheimer's disease, or cerebral amyloidosis, using the immunohistochemical technique. In addition, tyrosine hydroxylase and acetylcholinesterase were analyzed. This study shows marked neuropeptide changes in the hippocampal formation and the ventral cortex, whereas the dorsolateral neocortex was less affected. There was a considerable variation with regard to peptide expression among animals of the same age which was related to the variation in Abeta deposition. Dystrophic and varicose fibers containing galanin, neuropeptide Y, enkephalin, and especially cholecystokinin were commonly seen in close proximity to amyloid plaques. In addition, generalized changes were observed, such as increases of enkephalin and neuropeptide Y in stratum lacunosum moleculare and of neuropeptide Y, enkephalin, and dynorphin in mossy fibers. In contrast, cholecystokinin was decreased in mossy fibers. Comparatively small differences were observed between wild-type and transgenic mice with regard to tyrosine hydroxylase (noradrenergic but also dopaminergic fibers) and acetylcholine esterase (mainly cholinergic fibers). The increase of neuropeptides in dystrophic fibers in this model may represent a response to nerve injury caused by the amyloid accumulation and may reflect attempts to counteract degeneration by initiating protective and/or regenerative processes.

Unilateral urinary flow impairment at the pelviureteral junction: outcome of renal function with respect to therapeutic strategy.

OBJECTIVES: To evaluate the renal function outcome in children with unilateral hydronephrosis and urinary flow impairment at the pelviureteral junction with respect to the therapeutic strategy. METHODS: We retrospectively selected 45 children with iodine-123-hippuran renography performed at diagnosis and after 3 or more years of follow-up. All children had bilateral nonobstructive pattern findings on diuretic renography at follow-up. Eleven children were treated conservatively, and 34 underwent unilateral pyeloplasty. Split and individual renal function, measured by an accumulation index, was computed from background-corrected renograms for the affected and contralateral kidneys at diagnosis and the follow-up examination. RESULTS: Of 11 children treated conservatively, 9 had normal bilateral function at diagnosis, all had reached normal function at follow-up. Of the 34 operated kidneys, 12 (38%) had initially normal function that remained normal at the follow-up examination, and 22 had impaired function that had normalized at the follow-up examination in 15 (68%). The function of the contralateral kidneys was increased in 5 of 8 children with persistently abnormal affected kidneys. Pyeloplasty was performed in 23 children (68%) and 11 children (32%) younger and older than 1 year, respectively. The function of the affected kidneys increased in both groups, but normalization occurred only in the younger children. CONCLUSIONS: Of the children selected for conservative treatment, 82% had normal bilateral renal function at diagnosis that was normal in all at the follow-up examination. Of the children treated surgically, 65% had initially impaired function of the affected kidney that improved in 87% after pyeloplasty. Normalization of function was observed only in children who were younger than 1 year old at surgery. Persistently low function of the affected kidney was compensated for by the contralateral one regardless of the age at surgery.

Full-length rat amylin forms fibrils following substitution of single residues from human amylin.

Pancreatic amyloid deposits, composed of the 37 amino acid residue peptide amylin, represent an integral part of type 2 diabetes mellitus pathology. Human amylin (hA) forms fibrils in vitro and is toxic to cultured pancreatic islet beta-cells. In contrast, rat amylin (rA) which differs from hA by only six amino acid residues in the central region of the peptide, residues 18-29, does not form fibrils and is not cytotoxic. To elucidate the role of individual residues in fibril formation, we have generated a series of full-length rA variants and examined their ability to form fibrils in vitro. Single-residue substitutions with amino acids from corresponding positions of the hA sequence, i.e. R18H, L23F, or V26I, were sufficient to render rA competent for fibril formation albeit at a small yield. Combining two or three of these substitutions generally increased the ability to produce fibrils. Variant rA fibril morphologies were examined by negative stain electron microscopy and found to be similar to those generated by hA itself. Bulk assays, i.e. involving thioflavin-T fluorescence and sedimentation, showed that the amount of fibril formation was relatively small for these rA variants when compared to hA under the same conditions. Fibril growth was demonstrated by time-lapse atomic force microscopy, and MALDI-TOF mass spectrometry was used to verify that fibrils consisted of full-length peptide. Our observations confirm previous reports that the three proline residues play a dominant negative role in fibril formation. However, their presence is not sufficient to completely abolish the ability of rA to form fibrils, as each of the other three implicated residues (i.e. R18, L23 and V26) also has a dominant modulating effect.

Human urothelial cells grown on collagen adsorbed to surface-modified polymers.

OBJECTIVES: Tissue engineering methods can be applied to regenerate diseased, or congenitally missing, urinary tract tissues. Urinary tract tissue cell cultures must be established in vitro and adequate matrices, acting as cell carriers, must be developed. Although degradable and nondegradable polymer matrices offer adequate mechanical stability, they are not optimal for cell adherence and growth. To overcome this problem, extracellular matrix proteins, permitting cell adhesion and regulation of cell proliferation and differentiation, can be adsorbed to the surface-modified polymer. METHODS: In this study, nondegradable polymer films, poly(ethylene terephthalate), were used as an experimental model. Films were modified by graft polymerization of acrylic acid to subsequently allow collagen type I and III immobilization. The following adhesion, proliferation of human urothelial cells, and induction of their stratification were analyzed. RESULTS: Collagen adsorption on 0.2 microg/cm2 poly(acrylic acid)-grafted polymer films rendered the matrix apt for human urothelial cell adhesion and proliferation. Furthermore, stratification of urothelial cells was demonstrated on these surface-modified matrices. CONCLUSIONS: These results have shown that surface-modified polymer matrices can be used to act as cell carriers for cultured human urothelial cells. Such a cell-matrix construct could be applied in reparative surgery of the urinary tract.

Acrylic acid grafting and collagen immobilization on poly(ethylene terephthalate) surfaces for adherence and growth of human bladder smooth muscle cells.

In tissue engineering, degradable or non-degradable polymer matrices can act as cell-carrier-scaffolds. Cell adhesion and growth on these scaffolds can be promoted by immobilizing extracellular matrix proteins. Therefore, in this study, polymer poly(ethylene terephthalate) (PET) films were surface modified by graft polymerization of acrylic acid, to subsequently allow collagen (types I and III) immobilization and human smooth muscle cell expansion. The surfaces of PET were activated by plasma, followed by acrylic acid graft polymerization, resulting in covalently bound brushes, containing an average of either 0.22+/-0.1 or 5.93+/-0.87 microg/cm2 of poly(acrylic acid) (PAA). Subsequent electrostatic adsorption of collagen gave a surface concentration of 4.96 and 17.2 microg/cm2, respectively, as determined using radiolabelled 125I collagen. Both PET films grafted with 0.22 microg/cm2 of PAA with or without adsorbed collagen were apt for smooth muscle cell adhesion and proliferation. However, films grafted with 5.93 microg/cm2 were not. PAA-grafted PET films, onto which serum proteins of the culture medium adsorbed spontaneously, proved to be better matrices than films on which collagen has been immobilized. It, therefore, can be speculated that other serum proteins are more important than collagen for the human smooth muscle cell adhesion and growth on surface-modified polymer matrices.