Post-pregnancy family planning in Southeast Asia with a focus on novel training techniques.

Postpartum Family Planning is a critical strategy in the first 12 months post-childbirth. It aims to prevent unintended, closely spaced pregnancies and thereby help reducing maternal, neonatal as well as child morbidity and mortality. Despite its significance, many women remain without contraception despite a desire to avoid pregnancy. The World Health Organization suggests a 24-month inter-pregnancy interval after delivery, emphasizing the importance of contraceptive counselling from the antenatal to the immediate postpartum period. In South Asia, utilization of PPFP is minimal, even though the inclination towards birth spacing is high. Addressing these needs requires strengthening the capacity of service providers and promoting evidence-based practices. Novel training approaches in South Asia are Competency-Based On-the-Job Training, Group Based Training, Simulation Training, E-Learning, Mentorship Programs, and Continuing Professional Development. Among these, On-the-Job Training and Group Based Training were notably implemented. Emphasizing PPFP and ensuring proper training in this domain is essential for women's health and well-being post-delivery.

Pott's Paraplegia in a 2 Years Female: A Rare Presentation at an Early Age.

Introduction: Potts disease is extrapulmonary skeletal tuberculosis mostly affecting the thoracolumbar spine. It destroys the disc space, adjacent vertebral bodies, and spinal elements, leading to cord compression and paraplegia. Methods: This is a case report study of a 29-month-old toddler who presented to our hospital with bilateral lower limb weakness. Results: On clinical, laboratory, and radiological examination, she was diagnosed with Pott's spine, started on antitubercular therapy, and planned for surgery in her follow-up. Conclusion: Tuberculosis of the spine is still prevalent in developing countries, mainly in children. Complications of the disease can be devastating because of its ability to cause bone destruction, spinal deformity, and paraplegia. So, in a tuberculosis-endemic region, clinical suspicion should be there for Potts disease when a child presents with paraplegia of the lower limbs. Children can develop tuberculosis which can spread to the spine despite vaccination. The prognosis of spinal tuberculosis is improved by early diagnosis and rapid intervention.

Gastrointestinal symptoms among COVID-19 patients presenting to a primary health care center of Nepal: A cross-sectional study.

Background and Aim: Coronavirus disease 2019 (COVID-19) is a major public health problem causing significant morbidity and mortality worldwide. Apart from respiratory symptoms, gastrointestinal symptoms like nausea, vomiting, diarrhea, and abdominal discomfort are quite common among COVID-19 patients. The gastrointestinal tract can be a potential site for virus replication and feces a source of transmission. Thus, ignorance of enteric symptoms can hinder effective disease control. The objective of this study is to see the gastrointestinal manifestation of the disease and its effect on morbidity and mortality. Methods: This observational cross-sectional retrospective study was carried out among 165 laboratory-confirmed COVID-19 patients in primary health care of Gorkha, Nepal from March 1, 2021 to March 1, 2022. A systematic random sampling method was adopted while data were entered and analyzed by Statistical Package for Social Sciences version 21. Results: Of 165 patients, 97 patients (58.78%) had enteric involvement. Among gastrointestinal symptoms, diarrhea in 67 patients (40.6%) and nausea and/or vomiting in 66 patients (40%) were the most common symptoms, followed by abdominal pain in 27 patients (16.4%) and anorexia in 19 patients (11.5%). Of the majority of cases with gastrointestinal involvement, 63 (63%) were below 50 years of age. Many of the patients who received vaccination had gastrointestinal symptoms (79%). Complications like acute respiratory distress syndrome, shock, and arrhythmia developed in 9.7% of patients, with the death of eight patients. COVID-19 vaccination was associated with 4.32 times higher odds of having gastrointestinal involvement in subsequent COVID-19 infection. Conclusions: Diarrhea followed by nausea/vomiting was among the most common gastrointestinal symptoms affecting younger age groups in our study. Enteric symptoms were more common among vaccinated people rather than among nonvaccinated ones.

Prevalence and associated risk factors for tuberculosis among people living with HIV in Nepal.

BACKGROUND: Worldwide tuberculosis (TB) takes more lives than any other infectious diseases. WHO estimates around 68,000 incident TB cases in Nepal. However, in 2018 only around 27,232 new TB cases were reported in the national system, resulting around 40,768 incident TB cases missing every year in Nepal. National Tuberculosis Control Center carried out this study in anti-retroviral therapy (ART) sites to estimate the prevalence of TB and identify the associated risk factors for TB among the people living with Human Immunodeficiency Virus (PLHIVs) in Nepal. METHODS: It was a cross-sectional institution-based study conducted between March and August 2018. Six ART sites with high caseloads of PLHIVs were selected. PLHIVs who were equal or above 18 years of age and were in ART program at the selected study sites were considered eligible for the study. Diagnosis of tuberculosis among PLHIVs who agreed to participate in the study was carried out as per the National Tuberculosis Management Guideline of National Tuberculosis Program of Nepal. RESULTS: Among 403 PLHIVs, tuberculosis was diagnosed in 40 (9.9%) individuals. Median age of the participants was 36 (30-43) years. Prevalence of TB was significantly higher among male PLHIVs than female PLHIVs (13.6% Vs 5.8%; P = 0.02) and Dalit ethnic group compared to Brahmin/Chettri (22.0%Vs5.9%, P = 0.01). The risk of developing TB was found significant among those with HIV stage progressed to WHO stage 3 and 4 (OR = 4.85, P<0.001) and with the family history of TB (OR = 4.50, P = 0.002). CONCLUSIONS: Prevalence of TB among PLHIVs in Nepal was found 9.9%. Risk of developing TB was higher among PLHIVs who were male, Dalit, with HIV stage progressed to WHO stage 3 and 4 and with family history of TB. Hence, targeted interventions are needed to prevent the risk of developing TB among PLHIVs. Similarly, integrated, and comprehensive TB and HIV diagnosis and treatment services are needed for the management of TB/HIV co-infection in Nepal.

Aluminum Phosphide Poisoning, an Institutional Experience: Case Series.

BACKGROUND: The growing concern over pesticide use has been linked to self-harm and suicide especially in agricultural countries like Nepal.  Pesticides like organophosphorus and aluminum phosphide cause the majority of deaths. Although organophosphorus poisoning is common means for suicide, Aluminum phosphide poisoning is also encountered occasionally. Our case series aims to look after the intent of poisoning and the outcome of the patients following Aluminum phosphide poisoning. METHODS: This hospital record-based study includes Aluminum phosphide poisoning patients presenting to the emergency department of Scheer Memorial Adventist Hospital from first January 2017 to 31st December 2020. Data were analyzed using SPSS version-22. RESULTS:   Out of 25 total poisoning cases, most of them were female (60%) and married (56%).  The case fatality rate was 84% among which 20% cases were brought dead while 64% died in the hospital. All poisoning cases were suicidal in intent. CONCLUSIONS: Herein we report a case series on 25 Aluminum phosphide poisoning cases with high case fatality rate and all cases being suicidal in intent.

Prevalence of Diabetes in Tuberculosis Patients in Kathmandu Valley, Nepal.

In this descriptive cross-sectional study, the data on the prevalence of diabetes mellitus (DM) among tuberculosis (TB) patients at the Urban Directly Observed Treatment Centers in the Kathmandu, Bhaktapur, and Lalitpur districts of Nepal were collected. The prevalence of DM was assessed in 67 previously treated TB (PTTB) and 214 new TB patients. DM was diagnosed in 8 PTTB and 20 new TB patients. Clinical interviews identified 14 patients with DM, rapid blood glucose test was used to diagnose DM in 4 patients, and oral glucose tolerance test was used to diagnose DM in another 4 patients. Impaired glucose tolerance and impaired fasting glycemia were observed in 8 and 5 patients, respectively. The 18-24-year age group had the largest number of new TB patients (82, 38.3%). However, the incidence of DM among TB patients was higher in the >35-year age group. Moreover, DM was diagnosed in 24.2% of PTTB patients and in 23.1% of new TB patients. To determine the impact of DM screening in TB patients, a larger number of samples should be analyzed. DM screening for patients with TB is expected to start in developing countries. This should be initiated by conducting clinical interviews about DM and glucose tests using rapid kits.

The impact of active case finding on transmission dynamics of tuberculosis: A modelling study.

BACKGROUND: In the last decade, active case finding (ACF) strategies for tuberculosis (TB) have been implemented in many diverse settings, with some showing large increases in case detection and reporting at the sub-national level. There have also been several studies which seek to provide evidence for the benefits of ACF to individuals and communities in the broader context. However, there remains no quantification of the impact of ACF with regards to reducing the burden of transmission. We sought to address this knowledge gap and quantify the potential impact of active case finding on reducing transmission of TB at the national scale and further, to determine the intensification of intervention efforts required to bring the reproduction number (R0) below 1 for TB. METHODS: We adopt a dynamic transmission model that incorporates heterogeneity in risk to TB to assess the impact of an ACF programme (IMPACT TB) on reducing TB incidence in Vietnam and Nepal. We fit the models to country-level incidence data using a Bayesian Markov Chain Monte Carlo approach. We assess the impact of ACF using a parameter in our model, which we term the treatment success rate. Using programmatic data, we estimate how much this parameter has increased as a result of IMPACT TB in the implementation districts of Vietnam and Nepal and quantify additional efforts needed to eliminate transmission of TB in these countries by 2035. RESULTS: Extending the IMPACT TB programme to national coverage would lead to moderate decreases in TB incidence and would not be enough to interrupt transmission by 2035. Decreasing transmission sufficiently to bring the reproduction number (R0) below 1, would require a further intensification of current efforts, even at the sub-national level. CONCLUSIONS: Active case finding programmes are effective in reducing TB in the short term. However, interruption of transmission in high-burden countries, like Vietnam and Nepal, will require comprehensive incremental efforts. Complementary measures to reduce progression from infection to disease, and reactivation of latent infection, are needed to meet the WHO End TB incidence targets.

Psychological and clinical-epidemiological profile of poisoning in Nepal: an institutional experience.

Background  Poisoning has become a major public health problem, with the intent in most cases being self-harm and commit suicide. This study highlights the psychological and clinical-epidemiological profile of patients visiting Scheer Memorial Adventist Hospital after poisoning.  Methods  This retrospective record-based study was done among poisoning patients of a hospital in Nepal from 1st January 2018 to 31st December 2020. Data were analyzed using STATA version-15.  Results  Out of 134 total poisoning cases, 71 had consumed organophosphate compounds. The majority of the cases were female (59.2% in organophosphate groups, 69.8% in non-organophosphate groups). The circumstances of poisoning were mostly suicidal (95.8% in organophosphate groups, 90.5% in non-organophosphate groups) and the reasons for this being mostly family disputes. Organophosphate groups had 8.41 times higher odds of having complications when compared to non-organophosphorus compounds.   Conclusions  The majority of the poisoning cases were suicidal in nature and family disputes being the major reason for the intake of a poisonous substance. This demands that more attention be given to psychological and family counseling to resolve any disputes, as well as psychological management of poisoning cases after medical management. Also, a strong regulatory mechanism should be imposed to control the easy access to poisonous substances.

Should female community health volunteers (FCHVs) facilitate a response to gender-based violence (GBV)? A mixed methods exploratory study in Mangalsen, Nepal.

ABSTRACTAs part of a multisectoral response to gender-based violence (GBV), Nepal is testing the feasibility of having female community health volunteers (FCHVs) play a formal role in identifying GBV survivors and referring them to specialised services at health facilities. This study followed 116 FHCVs in Mangalsen municipality who attended a one-day orientation on GBV. Over the following year, data were collected from knowledge and attitude assessments of FCHVs, focus group discussions with FCHVs, and members of Mothers' Groups for Health. Most Significant Change stories were collected from FCHVs, in-depth interviews with stakeholders, and service statistics. Results show that the FCHVs' knowledge increased, attitudes changed, and confidence in addressing GBV grew. During the study period, FCHVs identified 1,253 GBV survivors and referred 221 of them to health facilities. In addition to assisting GBV survivors, FCHVs worked to prevent GBV by mediating conflicts and curbing harmful practices such as menstrual isolation. Stakeholders viewed FCHVs as a sustainable resource for identifying and referring GBV survivors to services, while women trusted them and looked to them for help. Results show that, with proper training and safety mechanisms, FCHVs can raise community awareness about GBV, facilitate support for survivors, and potentially help prevent harmful practices.

Comparative Yield of Tuberculosis during Active Case Finding Using GeneXpert or Smear Microscopy for Diagnostic Testing in Nepal: A Cross-Sectional Study.

This study compared the yield of tuberculosis (TB) active case finding (ACF) interventions applied under TB REACH funding. Between June 2017 to November 2018, Birat Nepal Medical Trust identified presumptive cases using simple verbal screening from three interventions: door-to-door screening of social contacts of known index cases, TB camps in remote areas, and screening for hospital out-patient department (OPD) attendees. Symptomatic individuals were then tested using smear microscopy or GeneXpert MTB/RIF as first diagnostic test. Yield rates were compared for each intervention and diagnostic method. We evaluated additional cases notified from ACF interventions by comparing case notifications of the intervention and control districts using standard TB REACH methodology. The project identified 1092 TB cases. The highest yield was obtained from OPD screening at hospitals (n = 566/1092; 52%). The proportion of positive tests using GeneXpert (5.5%, n = 859/15,637) was significantly higher than from microscopy testing 2% (n = 120/6309). (OR = 1.4; 95%CI = 1.12-1.72; p = 0.0026). The project achieved 29% additionality in case notifications in the intervention districts demonstrating that GeneXpert achieved substantially higher case-finding yields. Therefore, to increase national case notification for TB, Nepal should integrate OPD screening using GeneXpert testing in every district hospital and scale up of community-based ACF of TB patient contacts nationally.

How to reduce household costs for people with tuberculosis: a longitudinal costing survey in Nepal.

The aim of this study was to compare costs and socio-economic impact of tuberculosis (TB) for patients diagnosed through active (ACF) and passive case finding (PCF) in Nepal. A longitudinal costing survey was conducted in four districts of Nepal from April 2018 to October 2019. Costs were collected using the WHO TB Patient Costs Survey at three time points: intensive phase of treatment, continuation phase of treatment and at treatment completion. Direct and indirect costs and socio-economic impact (poverty headcount, employment status and coping strategies) were evaluated throughout the treatment. Prevalence of catastrophic costs was estimated using the WHO threshold. Logistic regression and generalized estimating equation were used to evaluate risk of incurring high costs, catastrophic costs and socio-economic impact of TB over time. A total of 111 ACF and 110 PCF patients were included. ACF patients were more likely to have no education (75% vs 57%, P = 0.006) and informal employment (42% vs 24%, P = 0.005) Compared with the PCF group, ACF patients incurred lower costs during the pretreatment period (mean total cost: US$55 vs US$87, P < 0.001) and during the pretreatment plus treatment periods (mean total direct costs: US$72 vs US$101, P < 0.001). Socio-economic impact was severe for both groups throughout the whole treatment, with 32% of households incurring catastrophic costs. Catastrophic costs were associated with 'no education' status [odds ratio = 2.53(95% confidence interval = 1.16-5.50)]. There is a severe and sustained socio-economic impact of TB on affected households in Nepal. The community-based ACF approach mitigated costs and reached the most vulnerable patients. Alongside ACF, social protection policies must be extended to achieve the zero catastrophic costs milestone of the End TB strategy.

The role of active case finding in reducing patient incurred catastrophic costs for tuberculosis in Nepal.

BACKGROUND: The World Health Organization (WHO) End TB Strategy has established a milestone to reduce the number of tuberculosis (TB)- affected households facing catastrophic costs to zero by 2020. The role of active case finding (ACF) in reducing patient costs has not been determined globally. This study therefore aimed to compare costs incurred by TB patients diagnosed through ACF and passive case finding (PCF), and to determine the prevalence and intensity of patient-incurred catastrophic costs in Nepal. METHODS: The study was conducted in two districts of Nepal: Bardiya and Pyuthan (Province No. 5) between June and August 2018. One hundred patients were included in this study in a 1:1 ratio (PCF: ACF, 25 consecutive ACF and 25 consecutive PCF patients in each district). The WHO TB patient costing tool was applied to collect information from patients or a member of their family regarding indirect and direct medical and non-medical costs. Catastrophic costs were calculated based on the proportion of patients with total costs exceeding 20% of their annual household income. The intensity of catastrophic costs was calculated using the positive overshoot method. The chi-square and Wilcoxon-Mann-Whitney tests were used to compare proportions and costs. Meanwhile, the Mantel Haenszel test was performed to assess the association between catastrophic costs and type of diagnosis. RESULTS: Ninety-nine patients were interviewed (50 ACF and 49 PCF). Patients diagnosed through ACF incurred lower costs during the pre-treatment period (direct medical: USD 14 vs USD 32, P = 0.001; direct non-medical: USD 3 vs USD 10, P = 0.004; indirect, time loss: USD 4 vs USD 13, P <  0.001). The cost of the pre-treatment and intensive phases combined was also lower for direct medical (USD 15 vs USD 34, P = 0.002) and non-medical (USD 30 vs USD 54, P = 0.022) costs among ACF patients. The prevalence of catastrophic direct costs was lower for ACF patients for all thresholds. A lower intensity of catastrophic costs was also documented for ACF patients, although the difference was not statistically significant. CONCLUSIONS: ACF can reduce patient-incurred costs substantially, contributing to the End TB Strategy target. Other synergistic policies, such as social protection, will also need to be implemented to reduce catastrophic costs to zero among TB-affected households.

Implementation of a psychosocial support package for people receiving treatment for multidrug-resistant tuberculosis in Nepal: A feasibility and acceptability study.

BACKGROUND AND OBJECTIVES: People receiving treatment for multidrug-resistant tuberculosis (MDR-TB) have high rates of depression. Psychosocial support in general, and treatments for depression in particular, form an important but neglected area of patient-centred care, and a key pillar in the global End TB strategy. We assessed the feasibility and acceptability of a psychosocial support package for people receiving treatment for MDR-TB in Nepal. METHODS: This feasibility study used a mixed quantitative and qualitative approach. We implemented the intervention package in two National Tuberculosis Programme (NTP) MDR-TB treatment centres and 8 sub-centres. We screened patients monthly for depression and anxiety (cut-off ≥24 and ≥17 respectively on the Hopkins Symptom Checklist) and also for low social support (cut-off ≤3 on the Multidimensional Scale of Perceived Social Support). Those who screened positive on either screening tool received the Healthy Activity Program (HAP), which uses brief counselling based on behavioural activation theory. Other aspects of the psychosocial package were information/education materials and group interactions with other patients. RESULTS: We screened 135 patients, of whom 12 (9%) received HAP counselling, 115 (85%) received information materials, 80 (59%) received an education session and 49 (36%) received at least one group session. Eight group sessions were conducted in total. All aspects of the intervention package were acceptable to patients, including the screening, information, group work and counselling. Patients particularly valued having someone to talk to about their concerns and worries. We were able to successfully train individuals with no experience of psychological counselling to deliver HAP. CONCLUSION: This psychosocial support package is acceptable to patients. The information materials we developed are feasible to deliver in the current NTP. However, the structured psychological counselling (HAP), is not feasible in the current NTP due to time constraints. This requires additional investment of counsellors in TB clinics.

Nano-structured polymers enhance bladder smooth muscle cell function.

It is the hypothesis of the present study that a biocompatible material which mimics the nanometer topography of native bladder tissue will enhance cellular responses and lead to better tissue integration in vivo. Previous in vitro studies have verified the ability to successfully reduce the surface feature dimensions of poly(lactic-co-glycolic acid) (PLGA) and poly(ether urethane) (PU) films into the nanometer regime via chemical etching procedures. Results from these studies also provided the first evidence that bladder smooth muscle cell adhesion was enhanced on chemically treated nano-structured polymeric surfaces compared to their conventional counterparts. Although cell adhesion is necessary for a biomaterial's success, subsequent cell functions (such as long-term cell growth and proliferation) are also critical for tissue ingrowth and long-term implant survival. The present in vitro study, therefore, investigated the function of bladder smooth muscle cells on these novel, nano-structured polymers over the expanded periods of 1, 3 and 5 days. Results indicated that cell number was influenced by both surface roughness and surface chemistry changes; the important contributor, however, was increased nanometer surface roughness. This claim is supported by the fact that cell number was enhanced on nano-structured compared to conventional PLGA and PU once chemistry changes were eliminated using casting techniques.

Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features.

Biomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also its topography. The cellular response to a biomaterial may be enhanced in synthetic polymer formulations by mimicking the surface roughness created by the associated nano-structured extra-cellular matrix components of natural tissue. As a first step towards this endeavor, the goal of the present in vitro study was to use these design parameters to develop a synthetic, nano-structured, polymeric biomaterial that promotes cell adhesion and growth for vascular applications. In a novel manner, poly(lactic-co-glycolic acid) (PLGA) (50/50wt% mix) was synthesized to possess a range (from micron to nanometer) of surface features. Reduction of surface features was accomplished by treating conventional PLGA with various concentrations of NaOH for select periods of time. Results from cell experiments indicated that, compared to conventional PLGA, NaOH treated PLGA enhanced vascular smooth muscle cell adhesion and proliferation. However, PLGA prepared by soaking in NaOH decreased endothelial cell adhesion and proliferation compared to conventional PLGA. After further investigation, this finding was determined to be a result of chemical (and not topographical) changes during polymer synthesis. Surface chemistry effects were removed while retaining nano-structured topography by using polymer/elastomer casting methods. Results demonstrated that endothelial and smooth muscle cell densities increased on nano-structured cast PLGA. For these reasons, the present in vitro study provided the first evidence that nano-structured surface features can significantly improve vascular cell densities; such design criteria can be used in the synthesis of the next-generation of more successful tissue-engineered vascular grafts.

Decreased fibroblast cell density on chemically degraded poly-lactic-co-glycolic acid, polyurethane, and polycaprolactone.

Select prolonged functions of fibroblasts leading to extensive fibrous tissue encapsulation can be detrimental to numerous implant applications, including materials designed for the bladder, vasculature, and bone. Specifically, overextended functions of fibroblasts at the tissue-implant interface for orthopedic applications lead to callus formation, fibrous encapsulation events, and ultimately soft (not desirable hard-bony) tissue juxtaposition. Such events result in insufficient regeneration of bone and compromise the overall success of the implant. The objective of the present in vitro study was to determine, for the first time, fibroblast densities on NaOH-treated poly-lactic-co-glycolic acid co-polymers (PLGA), HNO(3)-treated polyurethane (PU), and NaOH-treated polycaprolactone (PCL). Previous studies have demonstrated increased bladder, vascular, and bone cell densities on chemically treated compared to unaltered PLGA, PU, and PCL films. Results of this study provided evidence of decreased fibroblast numbers on chemically treated PLGA, PU, and PCL after time periods of up to 5 days. Examination of these substrates revealed that all chemically modified polymers possessed a high degree of nanometer surface roughness compared to their respective unaltered polymers. In contrast, other material properties (such as chemistry and wettability) were different when comparing chemically treated PLGA, PU, and PCL films. Since fibroblasts are anchorage-dependent cells whose adhesion is a critical prerequisite to the prolonged, extensive formation of a fibrous-tissue containing extracellular matrix, the present in vitro results of decreased fibroblast densities on chemically degraded PLGA, PU, and PCL suggest that these materials may be suitable materials for numerous tissue-engineering applications and, thus, deserve further investigation.

Nanostructured polymer/nanophase ceramic composites enhance osteoblast and chondrocyte adhesion.

Osteoblast (bone-forming cell) and chondrocyte (cartilage-synthesizing cell) adhesion on novel nanostructured polylactic/glycolic acid (PLGA) and titania composites were investigated in the present in vitro study. Nanostructured polymers were created by chemically treating micron-structured PLGA with select concentrations of NaOH for various periods of time. Dimensions of ceramics were controlled by utilizing either micron or nanometer grain size titania. Compared with surfaces with conventional or micron surface roughness dimensions, results provided the first evidence of increased osteoblast and chondrocyte adhesion on 100 wt% PLGA films with nanometer polymer surface roughness dimensions. Results also confirmed other literature reports of enhanced osteoblast adhesion on 100 wt% nanometer compared with conventional grain size titania compacts; however, the present study provided the first evidence that decreasing titania grain size into the nanometer range did not influence chondrocyte adhesion. Finally, osteoblast and chondrocyte adhesion increased on 70/30 wt% PLGA/titania composites formulated to possess nanosurface rather than conventional surface feature dimensions. The present study, thus, provided evidence that these nanostructured PLGA/titania composites may possess the ability to simulate surface and/or chemical properties of bone and cartilage, respectively, to allow for exciting alternatives in the design of prostheses with greater efficacy.

Enhanced functions of vascular and bladder cells on poly-lactic-co-glycolic acid polymers with nanostructured surfaces.

Polymers currently utilized for tissue engineering applications do not possess surfaces with nanostructured features. However, the tissue that the polymers will replace is composed of proteins that have nanometer dimensions. Undoubtedly, in situ, cells are accustomed to interacting with surface roughness values in the nanometer regime due to the presence of such proteins in natural tissue. Therefore, the objective of this paper was to design, synthesize and evaluate (using in vitro cellular models) poly-lactic-co-glycolic acid (PLGA) with nanostructured surface features to serve as the next generation of more efficient tissue engineered materials. For this purpose, nanostructured PLGA was created by treating conventional PLGA with various concentrations of NaOH for select periods of time. To eliminate surface chemistry changes created though the etching process, PLGA was cast from silastic molds of NaOH-treated nanostructured PLGA. Results provided the first evidence of increased numbers of vascular cells (specifically, endothelial and aortic smooth muscle cells) and bladder smooth muscle cells on nanostructured compared with conventional PLGA substrates. For this reason, the present results suggest, for the first time, that PLGA should incorporate a high degree of nanostructured surface roughness to enhance tissue regeneration for vascular and bladder applications.

Polymers with nano-dimensional surface features enhance bladder smooth muscle cell adhesion.

Previous studies investigating the design of synthetic bladder wall substitutes have involved polymers with micro dimensional structures. Since the body is made up of nano-structured components (e.g., extracellular matrix proteins), the focus of the present in vitro study was to design nano-structured polymers for use as synthetic bladder constructs that mimic the topography of natural bladder tissue. In order to complete this task, novel nano-structured biodegradable polymeric films of poly-lactic-co-glycolic-acid (PLGA), poly-ether-urethane (PU), and poly-caprolactone (PCL) were fabricated and separately treated with various concentrations of NaOH (for PLGA and PCL) and HNO(3) (for PU) for select time periods. These treatments reduced the polymer surface feature dimensions from conventional micron dimensions to biologically inspired nanometer dimensions. Select cytocompatibility properties of these biomaterials were tested in vitro. Results provide the first evidence that adhesion of bladder smooth muscle cells is enhanced as polymer surface feature dimensions are reduced into the nanometer range. In addition, surface analysis results reveal that the polymer nanometer surface roughness is the primary design parameter that increases bladder smooth muscle cell adhesion. For this reason, the "next generation" of tissue-engineered bladder constructs with increased efficacy should contain surfaces with nanometer (as opposed to micron) surface features.