TP53 Abnormalities and MMR Preservation in 5 Cases of Proliferating Trichilemmal Tumours.

Proliferating trichilemmal tumours (PTT) are defined by a benign squamous cell proliferation inside a trichilemmal cystic (TC) cavity. A possible explanation of this proliferative phenomenon within the cyst may be molecular alterations in genes associated to cell proliferation, which can be induced by ultraviolet radiation. Among other genes, alterations on TP53 and DNA mismatch repair proteins (MMR) may be involved in the cellular proliferation observed in PTT. Based on this assumption, but also taking into account the close relationship between the sebaceous ducts and the external root sheath where TC develop, a MMR, a p53 expression assessment and a TP53 study were performed in a series of 5 PTT cases, including a giant one. We failed to demonstrate a MMR disorder on studied PTT, but we agree with previous results suggesting increased p53 expression in these tumours, particularly in proliferative areas. TP53 alteration was confirmed with FISH technique, demonstrating TP53 deletion in most cells.

Melatonin as adjunctive therapy in the treatment of periodontitis associated with obesity.

AIMS: To study the effect of adjunctive systemic administration of melatonin to standard mechanical periodontal therapy in obese rats with experimental periodontitis. MATERIALS AND METHODS: In 42 Wistar rats with an initial body weight of 180 g., half (n = 21) were fed with a high-fat diet to induce obesity. In both obese and normal-weight groups, experimental periodontitis was subsequently induced through oral gavages with a combination of Porphyromonas gingivalis and Fusobacterium nucleatum. Both groups were randomly allocated to either no treatment or periodontal treatment consisting on standard mechanical debridement, with either adjunctive chlorhexidine or melatonin. Outcomes were evaluated by the changes in clinical parameters (probing depth modified gingival index, plaque dental index and bleeding on probing [BOP]), in bone resorption and in the levels of biomarkers in plasma and in gingival tissue (inflammatory cytokines, insulin, leptin, osteocalcin, osteopontin, plasminogen activator inhibitor-1, intercellular adhesion molecule 1, E-selectin and lipids). RESULTS: In the obese-periodontitis group, adjunctive melatonin administration resulted in reduced gingival inflammation and BOP, with significant reductions in probing depth and enhanced bone repair demonstrated by micro-CT (15% reduction in alveolar bone destruction) when compared with the same group treated with adjunctive CHX or the normal-weight rats with either melatonin or CHX. In this melatonin-treated obese-periodontitis group, a significant impact on biochemical biomarkers was also demonstrated in both gingival and plasma samples, when compared with the other groups, with significant reductions in pro-inflammatory cytokines. CONCLUSIONS: Adjunctive melatonin therapy significantly reduced alveolar bone loss and exerted a protective anti-inflammatory effect mainly in those experimental animals affected by the co-morbidity of periodontitis and obesity.

Citrus essential oils inhalation by mice: Behavioral testing, GCMS plasma analysis, corticosterone, and melatonin levels evaluation.

The use of orange essential oils (EOs) as a complementary treatment is very common in Brazilian popular culture. The levels of melatonin (MEL) and corticosterone (CORT) hormones were investigated simultaneously, by the Luminex™ immunoassay system in mice plasma, after Citrus aurantium and Citrus sinensis EOs inhalation for 30 min. The plasma was analyzed by headspace through gas chromatography coupled to mass spectrometry for investigation of the EO components. Mice were submitted to behavioral testing to research anxiolytic-like, sedative, and antidepressant-like effects. The inhalation of atmosphere obtained from vaporization of 10% solution of this Citrus EO separately did not affect MEL or CORT plasma levels; that is, the MEL and CORT levels did not present variation in function of the EO in the schedule used. On the other hand, the imipramine positive control used altered the level of MEL as expected. The EO constituents were detected in plasma at different ratios that is present in inhaled EO. Behavioral tests showed that the inhalation of 10% C. sinensis EO presents an anxiolytic-like and sedative effect. Thus, C. sinensis EO can be a valuable tool for treatment of the anxiety disturbs, apparently without interference with MEL and CORT physiological levels.

Obesity and periodontitis: An experimental study to evaluate periodontal and systemic effects of comorbidity.

BACKGROUND: Obesity and overweight have been associated with periodontitis. This study aims to evaluate periodontal and systemic effects of this association in a validated experimental model. METHODS: Twenty-eight male Wistar rats were randomly divided into four groups: 1) control group (Con) (fed with standard diet); 2) high-fat diet group (HFD) (fed with a diet containing 35.2% fat); 3) control group with induced periodontitis (Con-Perio); and 4) HFD group with induced periodontitis (HFD-Perio). To induce periodontitis, oral gavages with Porphyromonas gingivalis ATCC W83K1 and Fusobacterium nucleatum DMSZ 20482 were used. Periodontal outcomes were evaluated by inflammatory parameters, periodontal probing depth (PD), and modified gingival index (MGI). Systemic effects were evaluated by measuring levels of inflammatory cytokines, insulin, adiponectin, and leptin using multiplex immunoassays and levels of visfatin, resistin, lipid profiles, transaminases, and plasma endotoxin using colorimetric tests and the glucose tolerance test. RESULTS: Clinical parameters (PD and MGI) were significantly increased (P < 0.05) in the induced periodontitis groups compared with controls. The HFD-Perio group demonstrated significantly higher PD compared with Con-Perio group. Lipid profiles, cytokines, and adipocytokines showed significantly elevated levels in the HFD-Perio group compared with the other groups. Similarly, glucose levels in the HFD-Perio group were significantly higher (P < 0.05) than in the HFD group, and hepatic damage parameters demonstrated a tendency toward higher levels in the HFD-Perio group. CONCLUSION: Obesity and periodontitis demonstrated a comorbidity effect on both systemic inflammatory and metabolic dysregulation biomarkers, with increased glucose, dyslipidemia and hepatic damage.

Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival.

Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications.

Metabolic syndrome (MS) patients exhibit sleep/wake disturbances and other circadian abnormalities, and these may be associated with more rapid weight increase and development of diabetes and atherosclerotic disease. On this basis, the successful management of MS may require an ideal drug that besides antagonizing the trigger factors of MS could also correct the disturbed sleep-wake rhythm. Melatonin is an effective chronobiotic agent able to change the phase and amplitude of circadian rhythms. Melatonin has also significant cytoprotective properties preventing a number of MS sequelae in animal models of diabetes and obesity. A small number of controlled trials indicate that melatonin is useful to treat the metabolic and cardiovascular comorbidities of MS. Whether the recently introduced melatonergic agents (ramelteon, agomelatine, tasimelteon) have the potential for treating sleep disorders in MS patients and, more generally, for arresting the progression of disease, merits further investigation.

Laser microperforated biodegradable microbial polyhydroxyalkanoate substrates for tissue repair strategies: an infrared microspectroscopy study.

Flexible and biodegradable film substrates prepared by solvent casting from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) solutions in chloroform were microperforated by ultraviolet laser ablation and subsequently characterized using infrared (IR) microspectroscopy and imaging techniques and scanning electron microscopy (SEM). Both transmission synchrotron IR microspectroscopy and attenuated total reflectance microspectroscopy measurements demonstrate variations in the polymer at the ablated pore rims, including evidence for changes in chemical structure and crystallinity. SEM results on microperforated PHBHV substrates after cell culture demonstrated that the physical and chemical changes observed in the biomaterial did not hinder cell migration through the pores.

Melatonin effect on plasma adiponectin, leptin, insulin, glucose, triglycerides and cholesterol in normal and high fat-fed rats.

Melatonin effect on body weight progression, mean levels and 24-hr pattern of circulating adiponectin, leptin, insulin, glucose, triglycerides and cholesterol were examined in rats fed a normal or a high-fat diet. In experiment 1, rats fed a normal diet were divided into two groups: receiving melatonin (25 µg/mL drinking water) or vehicle for 9 wk. In experiment 2, animals were divided into three groups: two fed with a high-fat diet (35% fat) and melatonin (25 µg/mL) or vehicle in drinking water for 11 wk, while a third group was given a normal diet (4% fat). At the end of experiments, groups of eight rats were killed at six different time intervals throughout a 24-hr period. Melatonin administration for 9 wk decreased body weight gain from the 3rd wk on without affecting food intake. A significant reduction in circulating insulin, glucose and triglyceride mean levels and disrupted daily patterns of plasma adiponectin, leptin and insulin were observed after melatonin. In high fat-fed rats, melatonin attenuated body weight increase, hyperglycemia and hyperinsulinemia, as well as the increase in mean plasma adiponectin, leptin, triglycerides and cholesterol levels. The high-fat diet disrupted normal 24-hr patterns of circulating adiponectin, insulin and cholesterol, the effects on insulin and cholesterol being counteracted by melatonin. Nocturnal plasma melatonin concentration in control and obese rats receiving melatonin for 11 wk attained values 21-24-fold greater than controls. The results indicate that melatonin counteracts some of the disrupting effects of diet-induced obesity in rats.

24-Hour variation in gene expression of redox pathway enzymes in rat hypothalamus: effect of melatonin treatment.

The 24-h changes in medial basal hypothalamic (MBH) gene expression of redox pathway enzymes nitric oxide synthase (NOS)-1 and NOS-2, heme oxygenase (HO)-1 and HO-2, Cu/Zn- and Mn-superoxide dismutases (SOD) and catalase were examined in adult male Wistar rats kept under an alternating regimen of light/dark. Half of the animals received melatonin (approximately 60 microg/day) in the drinking water. After 1 month, rats were killed at six different time intervals, throughout a 24-h cycle. MBH mRNA levels were measured by real-time PCR analysis. In controls, gene expression of NOS-2 and HO-2 peaked at the early light phase while that of HO-1 showed a maximum at the middle of the dark phase. None of MBH mRNAs encoding NOS-1, Cu/Zn-SOD, Mn-SOD and catalase exhibited significant 24-h variations in control rats. Melatonin administration decreased significantly mRNAs for NOS-1, NOS-2, HO-1 and HO-2 as well as changed their 24-h profile. Melatonin augmented gene expression of the antioxidant enzymes Cu/Zn-SOD, Mn-SOD or catalase at certain time intervals only. The results are compatible with the view that the principal indirect (i.e. gene expression of redox pathway enzymes) effect of melatonin on redox pathway in the hypothalamus is mainly exerted via down-regulation of pro-oxidant enzyme mRNAs.

Effect of a high-fat diet on 24-hour pattern of circulating adipocytokines in rats.

We have shown a significant disruption of 24-h pattern of plasma pituitary, adrenal, and gonadal hormones in high-fat-fed rats. Our objective was to assess the effect of a high-fat diet (35% fat) on mean levels and 24-h pattern of several adipocytokines in rats. A normal diet-fed rats (4% fat) were used as controls. When body weight of high-fat-fed rats attained values about 25% higher than controls (after 66 days of treatment), the animals were killed at six different time intervals throughout a 24-h cycle. Plasma concentrations of insulin, adiponectin, interleukin (IL)-1, leptin, ghrelin, plasminogen activator inhibitor-1 (PAI-1), and monocyte chemoattractant protein-1 (MCP-1) were measured in a multianalyte profiling by using the Luminex-100 system. Tumor necrosis factor alpha (TNFalpha) and IL-6 were measured by enzyme-linked immunosorbent assay. A significant hyperglycemia developed in high-fat-fed rats, together with a significant increase in plasma insulin. Mean levels of plasma adiponectin, IL-1, IL-6, TNFalpha, and leptin augmented, and ghrelin decreased, in high-fat-fed rats. The normal daily pattern of plasma insulin, adiponectin, IL-1, IL-6, TNFalpha, leptin, ghrelin, and MCP-1 became disrupted in high-fat-fed rats. The results indicate that a high-fat diet may bring about signs of insulin resistance and mild inflammation in rats, together with the disruption in daily variations of circulating insulin and ghrelin, and of several adipocytokines including leptin, adiponectin, IL-1, IL-6, TNFalpha, and MCP-1.

Effect of aging on 24-hour pattern of stress hormones and leptin in rats.

This work analyzes the 24-hour changes of hypothalamic-pituitary-adrenal (HPA) axis activity and leptin release in aged rats. Three- and 22-month-old male Wistar rats were killed at 6 time intervals during a 24-hour cycle (n=8-10 rats/group). Aging augmented plasma ACTH while it decreased plasma and adrenal gland corticosterone levels. Plasma and adrenal corticosterone levels attained high levels during all the scotophase, concomitantly with the maxima in ACTH levels, whereas in aged rats only a brief plasma corticosterone peak at the early scotophase and no time of day variations of adrenal corticosterone were observed. Aging augmented circulating leptin, with a significant interaction "agextime" in the factorial ANOVA, i.e. only in young rats time of day changes were significant, with the lowest values of leptin at the middle of the light period and higher values at night. When plasma leptin was expressed on body weight basis, the age-related differences became not significant but the daily pattern of plasma leptin found in young rats persisted. Plasma and adrenal corticosterone levels correlated significantly with plasma ACTH only in young rats. Likewise, plasma leptin correlated with plasma corticosterone only in young rats. These changes can be attributed to a disrupting effect of aging on the homeostatic mechanisms modulating HPA activity and leptin release.

Effect of a high-fat diet on 24-h pattern of circulating levels of prolactin, luteinizing hormone, testosterone, corticosterone, thyroid-stimulating hormone and glucose, and pineal melatonin content, in rats.

Circadian rhythmicity is affected in obese subjects. This article analyzes the effect of a high-fat diet (35% fat) on 24-h changes circulating prolactin, luteinizing hormone (LH), testosterone, corticosterone, thyroid-stimulating hormone (TSH) and glucose, and pineal melatonin content, in rats. When body weight of rats reached the values of morbid obesity, the animals were sacrificed at six different time intervals throughout a 24-h cycle, together with age-matched controls fed a normal diet (4% fat). Plasma hormone levels were measured by specific radioimmunoassays and glucose concentration by an automated glucose oxidase method. In rats under a high-fat diet, a significant disruption of the 24-h pattern of plasma TSH, LH, and testosterone and a slight disruption of prolactin rhythm were found. Additionally, high-fat fed rats showed significantly lower total values of plasma TSH and testosterone and absence of correlation between testosterone and circulating LH levels. Plasma corticosterone levels increased significantly in high-fat fed rats and their 24-h variation became blunted. In obese animals, a significant hyperglycemia developed, individual plasma glucose values correlating with circulating corticosterone in high-fat fed rats only. The amplitude of the nocturnal pineal melatonin peak decreased significantly in high-fat fed rats. The results underlie the significant effects that obesity has on circadian organization of hormone secretion.

[Larrad biliopancreatic diversion. Description of an rat experimental model]. / Derivación biliopancreática de Larrad. Descripción de un modelo experimental en la rata.

UNLABELLED: OBJECTIVE.: To validate the experimental model of Larrad-biliopancreatic diversion (LBPD) and to analyze weight gain and mortality in rats fed with non- supplemented diets. MATERIAL AND METHOD: Control (6) and experimental (10) male Wistar rats were used. The experimental group was operated on using the human LBPD adapted for rats: Subcardial gastrectomy, a short biliopancreatic channel created at 5 cm from Treitz angle and common channel at 5 cm from ileocecal valve. After surgery recovery (7 days) the rats were fed ab libitum with a standard non-supplemented diet (without proteins, minerals or vitamins). Percentage of weight lost or gained up to the end of the experiment was analyzed. RESULTS: The control animals gained weight progressively from 13.1 +/- 2.4% at day 7 to 58 +/- 9.2% at day 63, when the animals were sacrificed. After LBPD, mortality was 50% at day 25 +/- 17.5(range, 14-56), no significant differences in the percentage of weight lost being found between surviving (-38.9 +/- 14.2%) and non-surviving rats (-29 +/- 5.6%; p = 0.192). Of the surviving animals, 80% progressively lost weight reaching a maximum loss between day 63 (-42.3 +/- 8%) and 70 (-44.1 +/- 9.7%), and 20% lost weight until day 35 and gained over 7% of body weight until sacrifice (day 147). CONCLUSIONS: An experimental model of LBPD in rats is technically feasible. Both mortality and percentage weight loss are not directly related. The bowel adaptation mechanism could mediate the percentage of weight regain in operated rats.

Effects of moderate consumption of distilled and fermented alcohol on some aspects of neuroimmunomodulation.

Alcoholic beverages are characterized by their fermented versus distilled origin and also by their degree of alcohol. The toxic effects of chronic alcohol consumption have been widely studied. However, there is less evidence about possible beneficial effects of moderate alcohol intake. This work was aimed at evaluating the effects of moderate alcohol consumption (beer or ethanol) on plasma hormone concentrations, blood and thymus lymphocyte phenotypes and brain neurotransmitter levels. For this purpose, 40 adult Wistar male rats were administered ethanol or beer for 4 weeks (experimental groups). Age-matched rats were administered beer without alcohol or water to be used as controls. Rats were killed by decapitation and plasma from the trunk blood was collected to measure plasma prolactin, growth hormone and ACTH concentrations by homologous specific double antibody radioimmunoassays. Thymus and blood lymphocyte subsets were measured by flow cytometry. Neurotransmitter concentrations [dopamine, gamma-aminobutyric acid (GABA) and taurine] were measured by high pressure liquid chromatography in the median eminence and the pituitary. Blood and thymus lymphocyte subsets were not significantly changed by either ethanol or beer consumption, compared to controls. Plasma prolactin levels significantly decreased in ethanol-administered groups (p < 0.05) compared to control animals drinking water, although plasma levels of growth hormone and ACTH were not modified by either alcohol used. Dopamine and GABA concentrations in the median eminence or in the adenohypophysis remained unmodified by moderate beer or ethanol consumption. However, taurine concentration was significantly increased in the pituitary (p < 0.05) in the group drinking ethanol compared to those groups drinking beer with or without alcohol. These data suggest that moderate alcohol consumption may change the regulatory mechanism of prolactin secretion. Whether these modifications have a physiological significance deserves further research.

Neuroendocrine-immune correlates of circadian physiology: studies in experimental models of arthritis, ethanol feeding, aging, social isolation, and calorie restriction.

Virtually all neuroendocrine and immunological variables investigated in animals and humans display biological periodicity. Circadian rhythmicity is revealed for every hormone in circulation as well as for circulating immune cells, lymphocyte metabolism and transformability, cytokines, receptors, and adhesion molecules. Clock genes, notably the three Period (Per1/Per2/Per3) genes and two Cryptochrome (Cry1/Cry2) genes, are present in immune and endocrine cells and are expressed in a circadian manner in human cells. This review discusses the circadian disruption of hormone release and immune-related mechanisms in several animal models in which circulating cytokines are modified including rat adjuvant arthritis, social isolation in rats and rabbits and alcoholism, the aging process and calorie restriction in rats. In every case the experimental manipulation used perturbed the temporal organization by affecting the shape and amplitude of a rhythm or by modifying the intrinsic oscillatory mechanism itself.

24-Hour rhythm in gene expression of nitric oxide synthase and heme-peroxidase in anterior pituitary of ethanol-fed rats.

Chronic exposure of rats to ethanol results in significant changes in pituitary hormone secretion. However, identification of the site(s) and mechanism of action of ethanol to induce these effects remains elusive. Free radical damage at the adenohypophyseal level may play a role in the decline in serum gonadotropin levels in ethanol-fed rats. Since 24-h changes in redox state occurred, we analyzed the 24-h changes in pituitary gene expression of the prooxidant enzymes nitric oxide synthase (NOS) 1 and 2, and of heme oxygenase-1 (HO-1) enzyme, and in plasma NO(2)(-) and NO(3)(-) (NO(x)) levels, in ethanol and control rats. Male rats, 35-day-old, received a liquid diet for 4 weeks. The ethanol-fed group received a similar diet to controls except for that maltose was isocalorically replaced by ethanol. Animals were killed at six time intervals during a 24-h cycle. Anterior pituitary mRNA levels encoding NOS1, NOS2 and HO-1 were measured by real-time PCR analysis. Plasma NO(x) concentration was determined by the Griess reaction. Ethanol feeding of prepubertal rats changed significantly the 24-h pattern of expression of NOS1, NOS2 and HO-1 in the adenohypophysis and augmented NOS2 and HO-1 mRNA levels. Peak values for the three enzymes in ethanol-fed rats occurred at the beginning of the scotophase (i.e., at 21:00 h). Ethanol feeding augmented mean values plasma NO(x) levels with a maximum at 13:00 h while in controls a biphasic pattern was observed, with peaks at 09:00 h and 17:00-21:00 h. One of the mechanisms by which ethanol augments oxidative damage in the adenohypophysis may include overproduction of nitric oxide and carbon monoxide.

Cadmium-induced changes in Per 1 and Per 2 gene expression in rat hypothalamus and anterior pituitary: effect of melatonin.

Chronic cadmium (Cd) administration affects the circadian release of pituitary hormones in rats. To assess whether Cd modifies expression of two major clock genes, period (Per) 1 and Per 2, in the hypothalamic-pituitary unit and to what extent the changes could be prevented by melatonin, rats were exposed to CdCl(2) (5ppm in drinking water) with or without melatonin (3 microg/mL drinking water) for 1 month and were killed at two time intervals, i.e. a the beginning of the rest span (09:00h) and at the middle of the activity span (01:00h). Hypothalamic and pituitary mRNA levels encoding Per 1 and Per 2 were measured by real-time PCR analysis. Cd treatment decreased expression of hypothalamic Per 1 gene at both time intervals, of hypothalamic Per 2 gene at 01:00h, and of adenohypophysial Per 1 and Per 2 genes at 09:00h. Melatonin administration counteracted most of the effects of Cd and augmented hypothalamic Per 2, and adenohypophysial Per 1 and Per 2 gene expression. The results indicate that Cd administered chronically in the drinking water to rats affected expression of clock genes in the hypothalamic-pituitary unit, an effect prevented by melatonin.

Immune response after experimental allergic encephalomyelitis in rats subjected to calorie restriction.

Male Lewis rats (6 weeks-old) were submitted to a calorie restriction equivalent to 33% or 66% of food restriction. Fifteen days later, groups of 7 animals were injected with complete Freund's adjuvant plus spinal cord homogenate (SCH) to induce experimental allergic encephalomyelitis (EAE) or with complete Freund's adjuvant alone. EAE was defined solely on clinical grounds. Rats were assessed daily for clinical signs of EAE and were killed on day 15 after immunization. Both diet and SCH injection diminished body weight significantly. In contrast to rats receiving a normal diet or a 33% calorie-restricted diet, rats subjected to severe calorie restriction did not exhibit clinical signs of EAE. Concomitantly with the lack of disease manifestation, 66% of calorie-restricted rats injected with SCH showed significantly less splenic and lymph node mitogenic response to concanavalin A (Con A) and a higher splenic response to lipopolysaccharide. Fewer splenic, lymph node and thymic CD4+ cells, greater numbers of splenic and lymph node CD8+ and CD4+- CD8+ cells, and fewer splenic T, B and T-B cells, and lymph node and thymic B and T-B cells were observed. There was impaired interferon (IFN)-gamma production occurred in the three examined tissues. The results are compatible with the view that the acute phase of EAE can be curtailed by severe calorie restriction, presumably through impaired IFN-gamma production.

A Nd:YAG laser-microperforated poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-basal membrane matrix composite film as substrate for keratinocytes.

Epithelia cultured for the treatment of ulcers, burns and for gene therapy applications require a flexible biomaterial for growth and transplantation that is adaptable to body contours. We tested several materials and found that a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) polyester provided support for keratinocytes, although adhesion to this material proved to be suboptimal. Since epithelia adhere to the mesoderm through basal membranes, we engineered a basal membrane surrogate by preparing composites of PHBHV with basal membrane matrix (BMM). To allow cell migration into injuried areas the polyester film was micromachined to insert high-density micropores through a Nd:YAG laser ablation process. These flexible composites provided firm attachment for keratinocytes from the outer root sheath of human hair allowing keratinocyte migration through micropores. Films of microperforated PHBHV-BMM may be of use for the replacement of diseased or injured skin epithelia.