Wound-triggered shape change microgels for the development of enhanced biomimetic function platelet-like particles.

Platelets play a pivotal role in hemostasis and wound healing and conditional shape change is an important component of platelet functionality. In normal circumstances, platelets travel through the circulatory system in an inactive rounded state, which enables platelets to easily move to vessel walls for attachment. When an injury occurs, platelets are prompted by molecules, such as thrombin, to shift into a stellate shape and increase exposure of fibrin-binding receptors. When active, platelets promote hemostasis and clot retraction, which enhances clot stability and promotes healing. However, in conditions where platelets are depleted or hyporeactive, these functions are diminished and lead to inhibited hemostasis and healing. To treat platelet depletion, our group developed platelet-like particles (PLPs) which consist of highly deformable microgels coupled to fibrin binding motif. However, first generation PLPs do not exhibit wound-triggered shape change like native platelets. Thus, the objective of these studies was to develop a PLP formulation that changes shape when prompted by thrombin. To create thrombin-sensitive PLPs (TS-PLPs), we incorporated a thrombin-cleavable peptide into the microgel body and then evaluated PLP properties before and after exposure to thrombin including morphology, size, and in vitro clot retraction. Once thrombin-prompted shape change ability was confirmed, the TS-PLPs were tested in vivo for hemostatic ability and subsequent wound healing outcomes in a murine liver trauma model. We found that TS-PLPs exhibit a wound-triggered shape change, induce significant clot retraction following exposure to thrombin and promote hemostasis and healing in vivo after trauma.

Hydrolytic hydrogels tune mesenchymal stem cell persistence and immunomodulation for enhanced diabetic cutaneous wound healing.

Diabetes is associated with an altered global inflammatory state with impaired wound healing. Mesenchymal stem/stromal cells (MSC) are being explored for treatment of diabetic cutaneous wounds due to their regenerative properties. These cells are commonly delivered by injection, but the need to prolong the retention of MSC at sites of injury has spurred the development of biomaterial-based MSC delivery vehicles. However, controlling biomaterial degradation rates in vivo remains a therapeutic-limiting challenge. Here, we utilize hydrolytically degradable ester linkages to engineer synthetic hydrogels with tunable in vivo degradation kinetics for temporally controlled delivery of MSC. In vivo hydrogel degradation rate can be controlled by altering the ratio of ester to amide linkages in the hydrogel macromers. These hydrolytic hydrogels degrade at rates that enable unencumbered cutaneous wound healing, while enhancing the local persistence MSC compared to widely used protease-degradable hydrogels. Furthermore, hydrogel-based delivery of MSC modulates local immune responses and enhances cutaneous wound repair in diabetic mice. This study introduces a simple strategy for engineering tunable degradation modalities into synthetic biomaterials, overcoming a key barrier to their use as cell delivery vehicles.

Biomaterial therapeutic strategies for treatment of bacterial lung infections.

Bacterial infections of the lung frequently occur as a secondary infection to many respiratory viral infections and conditions, including influenza, COVID-19, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). Currently, clinical standard treats bacterial infections of the lung with antibiotic drugs. However, the use of broad-spectrum antibiotics can disrupt host microbiomes, lead to patient discomfort, and current clinical settings face the constantly increasing threat of drug-resistant bacteria. Biofilms further obstruct effective treatment due to their protective matrix layer, which shields bacteria from both the host immune system and antimicrobial drugs and subsequently promotes drug resistance. Alternative antimicrobial agents, including bacteriophages and antimicrobial peptides, have been utilized to treat drug-resistant bacteria. However, these antimicrobial agents have significant limitations pertaining to their ability to arrive at infection sites without compromised function and ability to persist over an extended period to fully treat infections. Enhanced delivery strategies present great promise in addressing these issues by using micro/nanoparticle carriers that shield antimicrobial agents in transit and result in sustained release, enhancing subsequent therapeutic effect and can even be modulated to be multi-functional to further improve recovery following bacterial infection.

Development of biomimetic antimicrobial platelet-like particles comprised of microgel nanogold composites.

A blood clot is formed in response to bleeding by platelet aggregation and adherence to fibrin fibers. Platelets contract over time, stabilizing the clot, which contributes to wound healing. We have developed platelet-like particles (PLPs) that augment clotting and induce clot retraction by mimicking the fibrin-binding capabilities and morphology of native platelets. Wound repair following hemostasis can be complicated by infection; therefore, we aim to augment wound healing by combining PLPs with antimicrobial gold to develop nanogold composites (NGCs). PLPs were synthesized with N-isopropylacrylamide (NIPAm)/co-acrylic acid in a precipitation polymerization reaction and conjugated to a fibrin-specific antibody. Two methods were employed to create NGCs: 1) noncovalent swelling with aqueous gold nanospheres, and 2) covalent seeding and growth. Since the ability of PLPs to mimic platelet morphology and clot retraction requires a high degree of particle deformability, we investigated how PLPs created from NGCs affected these properties. Cryogenic Scanning Electron Microscopy (cryoSEM) and atomic force microscopy (AFM) demonstrated that particle deformability, platelet-mimetic morphology and clot retraction were maintained in NGC-based PLPs. The effect of NGCs on bacterial adhesion and growth was assessed with antimicrobial assays. These results demonstrate NGCs fabricated through noncovalent and covalent methods retain deformability necessary for clot collapse and exhibit some antimicrobial potential. Therefore, NGCs are promising materials for preventing hemorrhage and infection following trauma.

Nanosilver composite pNIPAm microgels for the development of antimicrobial platelet-like particles.

Platelets crucially facilitate wound healing but can become depleted in traumatic injury or chronic wounds. Previously, our group developed injectable platelet-like particles (PLPs) comprised of highly deformable, ultralow crosslinked pNIPAm microgels (ULCs) coupled to fibrin binding antibodies to treat post-trauma bleeding. PLP fibrin-binding facilitates homing to sites of injury, promotes clot formation, and, due to high particle deformability, induces clot retraction. Clot retraction augments healing by increasing clot stability, enhancing clot stiffness, and promoting cell migration into the wound bed. Because post-traumatic healing is often complicated by infection, the objective of these studies was to develop antimicrobial nanosilver microgel composite PLPs to augment hemostasis, fight infection, and promote healing post-trauma. A key goal was to maintain particle deformability following silver incorporation to preserve PLP-mediated clot retraction. Clot retraction, antimicrobial activity, hemostasis after trauma, and healing after injury were evaluated via confocal microscopy, colony-forming unit assays, a murine liver trauma model, and a murine full-thickness injury model in the absence or presence of infection, respectively. We found that nanosilver incorporation does not affect base PLP performance while bestowing significant antimicrobial activity and enhancing infected wound healing outcomes. Therefore, Ag-PLPs have great promise for treating hemorrhage and improving healing following trauma.

Immigration Transition and Cognitive Symptoms During Menopausal Transition.

Many studies have been conducted to investigate the effect of cultural influences on menopausal symptoms; however, associations between immigration transition and cognitive symptoms have rarely been uncovered. This secondary analysis aimed to determine these associations among 1,054 midlife women in the United States using the data from two national Internet surveys. The surveys included multiple questions on immigration transition, health and menopausal status, and the Cognitive Symptom Index for Midlife Women. The data analysis was performed using descriptive and inferential statistics including hierarchical multiple regression analyses. Nonimmigrants had larger numbers and higher severity scores of total cognitive symptoms than immigrants (p < .001). Immigration status explained 1.28% of the total variances in the total numbers and 1.46% of the total variances in the total severity scores of total cognitive symptoms (p < .001). The study supported significant associations between immigration transition and cognitive symptoms of women at midlife.

Issues in Recruiting and Retaining Asian American Breast Cancer Survivors in a Technology-Based Intervention Study.

BACKGROUND: Difficulties in recruiting and retaining Asian Americans in traditional research have been well documented. Despite an increasing number of technology-based cancer studies among racial/ethnic minorities, little is still known about potential issues in recruiting and retaining racial/ethnic minority cancer survivors for technology-based intervention research. OBJECTIVE: This discussion article aims to examine issues in recruiting and retaining a group of racial/ethnic minorities-Asian American breast cancer survivors-for a technology-based intervention study. METHODS: The parent study is an ongoing large-scale, national-scope, technology-based intervention study among a target number of 330 Asian American breast cancer survivors. During the recruitment and retention process, research diaries were written by research team members, and the written records of weekly research team meetings were kept. The written records were analyzed using a content analysis. Then, the themes were used to support the discussion points made in the article. RESULTS: There existed subethnic differences in research participation; it was easier to recruit Chinese participants compared with other subethnic groups. The use of culturally matched research team members and multiple languages was essential. Gatekeepers were also elemental for recruitment and retention. Various motivation strategies were needed to retain the participants. Each subethnic group used different communication apps. Finally, trust building was essential to retain the participants in the intervention. CONCLUSIONS: Researchers need to consider these practical issues in future technology-based intervention research. IMPLICATIONS FOR PRACTICE: These issues need to be considered in future program/intervention development and implementation among racial/ethnic minority cancer survivors.

Biomimetic antimicrobial material strategies for combating antibiotic resistant bacteria.

Antibiotic drugs have revolutionized the field of medicine for almost 90 years. However, continued use has led to the rise of antibiotic resistant bacteria, motivating the need for alternative treatments. Several strategies to combat this phenomenon have been investigated, with biomimetic strategies gaining significant appeal due to inherent compatibility with physiologically relevant environments. In this review, we will discuss current antimicrobial strategies and then present an overview on biomimetic antimicrobial material-based strategies for combating antibiotic resistant bacteria.

The Preliminary Efficacy of a Technology-Based Cancer Pain Management Program Among Asian American Breast Cancer Survivors.

With few existing technology-based programs to support cancer pain management, the need for culturally tailored programs to support ethnic minority cancer survivors has been highlighted. The purpose of this study was to explore the preliminary efficacy of the technology-based CAncer Pain management support Program for Asian American survivors of breast cancer, a technology-based cancer pain management program, in improving the cancer pain experience of Asian American breast cancer survivors. This pilot study adopted a randomized repeated-measures pretest/posttest control group design with a sample of 94 Asian American breast cancer survivors. Study measures included the Brief Pain Inventory-Short Form, Support Care Needs Survey-34 Short Form, and Mishel Uncertainty in Illness Scale-Community. Data were analyzed using descriptive and inferential statistics including repeated-measures analysis of covariance. Although there were no significant differences in pain, there were significant changes in perceived isolation (F = 9.937, P < .01), personal resources (F = 6.612, P < .05), support care need (F = 8.299, P < .01), and degree of uncertainty (F = 8.722, P < .01) in the intervention group from pretest to posttest. These findings support the positive effects of CAncer Pain management support Program for Asian American survivors of breast cancer on the cancer pain experience of Asian American breast cancer survivors.

Recruitment and Retention of Asian Americans in Web-Based Physical Activity Promotion Programs: A Discussion Paper.

Web-based interventions that promote physical activity have been tested in various populations and proven effective. However, information on recruiting and retaining ethnic minorities in these interventions is limited. This study discusses practical issues in recruitment and retention of Asian Americans using three strategies: (1) only Web-based intervention (Group 1), (2) one with Fitbit Charge HR (Group 2), and (3) one with Fitbit Charge HR and office visits (Group 3). Recruitment and retention rates, minutes of weekly research team meetings, and the researchers' memos were collected. Retention rates were analyzed using descriptive statistics, and the minutes and memos were content analyzed following Weber's methods. Retention rates varied by the end of the first (12% in Group 3, 36.9% in Group 2) and third month (0% in Group 3, 36.9% in Group 2). The practical issues were (1) difficulties in recruitment across strategies, (2) the necessity of using community consultants/leaders across strategies, (3) subethnic differences across strategies, (4) timing issues across strategies, (5) Fitbit as a facilitator with several hindrances, and (6) office visits as an inhibitor. Fitbits with user guidelines and community consultants'/leaders' involvement are proposed for future Web-based interventions to promote physical activity in Asian Americans.

Challenges in a Technology-Based Cancer Pain Management Program Among Asian American Breast Cancer Survivors.

This paper aims to discuss the challenges faced during a pilot study that tested a technology-based cancer pain management program among Asian American survivors of breast cancer and provide directions for future technology-based interventions for racial and ethnic minorities. Data consisting of research diaries and meeting minutes underwent content analysis to extract themes that reflected the challenges. The challenges included those related to (1) diversities within the population of Asian American survivors of breast cancer; (2) survivors' treatment and healing process; (3) Internet resources from the participants' countries of origin; (4) building trust between researchers and participants/gatekeepers; (5) fidelity of the intervention; and (6) cultural sensitivity. Future design and implementation of technology-based programs for racial and ethnic minorities must consider these challenges.

Racial/Ethnic Differences in Cognitive Symptoms During the Menopausal Transition.

The purpose of this study was to explore racial/ethnic differences in midlife women's cognitive symptoms among four major racial/ethnic groups in the United States and to determine multiple factors that influenced the women's cognitive symptoms. This was a secondary analysis of the data from two larger studies among 1,054 midlife women. The instruments included multiple questions on background characteristics and health and menopausal status, and the Cognitive Symptom Index for Midlife Women. The data were analyzed using multiple logistic and Poisson regression analyses. There existed significant racial/ethnic differences in the total numbers and total severity scores of cognitive symptoms ( p < .01); non-Hispanic Asians had significantly lower total numbers and total severity scores compared with other racial/ethnic groups. Socioeconomic status and health and menopausal status were significant factors that influenced cognitive symptoms across racial/ethnic groups ( p < .05). Further studies on racial/ethnic differences in cognitive symptoms are needed with diverse groups of midlife women.

The relationships of multiple factors to menopausal symptoms in different racial/ethnic groups of midlife women: The structural equation modeling.

The purpose of the present study was to examine the relationships of multiple factors to menopausal symptoms in different racial/ethnic groups of midlife women. This secondary analysis was conducted with the data from 980 midlife women that were collected from 2005 to 2013 using the Midlife Women's Symptom Index. Structural equation modeling was used to analyze the data. The model had the highest fit indices for non-Hispanic (NH) White midlife women, and prominent racial/ethnic differences were observed in the relationships of multiple factors to menopausal symptoms. In all racial/ethnic groups (except in Hispanic women), perceived health status was significantly positively associated with menopausal symptoms (ß = -0.149 for NH African-American; ß = -0.207 for NH Asians; ß = -0.162 for NH Whites). Body mass index was significantly positively associated with menopausal symptoms only in NH Asians (ß = 0.118) and Hispanics (ß = 0.210). The racial/ethnic differences in the relationships of multiple factors to menopausal symptoms could have resulted from the different cultural contexts in which women undergo during their menopausal transitions. Further cultural studies on the associations of racial/ethnic-specific factors with menopausal symptoms would help in understanding possible causes for racial/ethnic differences in the factors significantly associated with menopausal symptoms.

Decreasing menopausal symptoms of Asian American breast cancer survivors through a technology-based information and coaching/support program.

OBJECTIVE: One of the most prevalent and distressing symptoms after breast cancer treatment is menopausal symptoms. Asian American breast cancer survivors have lower quality of life and often receive inadequate management of menopausal symptoms compared to other racial/ethnic groups. Technology-based programs could be a solution to fill the gap in care. The purpose of this study was to test the efficacy of a technology-based information and coaching/support program on menopausal symptoms of Asian American breast cancer survivors. METHODS: This study adopted a randomized pretest/post-test group design among 91 Asian American breast cancer survivors (42 in an intervention group who used the program and the American Cancer Society Web site and 49 in a control group who used only the American Cancer Society Web site). The intervention was a theory-driven and culturally tailored intervention program that aimed to provide information and coaching/support using computers and mobile devices. Multiple instruments were used to measure background characteristics and menopausal symptoms at pretest, post 1-month, and post 3 months. An intent-to-treat linear mixed-model growth curve analysis was used to analyze the data. RESULTS: The intervention group showed a significant decrease in the distress scores of menopausal symptoms over time: physical (ß = -0.07, P = 0.08), psychological (ß = -0.13, P = 0.05), psychosomatic (ß = -0.17, P = 0.06), and total symptoms (ß = -0.19, P = 0.01). Theory-based variables including attitudes, social influences, and self-efficacy partially mediated the impact of the intervention on the distress scores of menopausal symptoms (P < 0.10). CONCLUSIONS: The program was effective in alleviating menopausal symptoms of Asian American breast cancer survivors.

What to Consider in a Culturally Tailored Technology-Based Intervention?

The purpose of this article is to identify practical issues in implementing a culturally tailored technology-based intervention among Asian American survivors of breast cancer. In a large-scale technology-based breast cancer intervention study, research team members wrote memos on issues in implementing a culturally tailored technology-based intervention and plausible reasons for the issues. Then, the content of the research diaries was analyzed, along with written records of the research team. The practical issues found in the research process included those related to (1) technology literacy and preferences; (2) language issues; (3) cultural attitudes, beliefs, and values; (4) intervention staff competence; (5) security and confidentiality issues; and (6) time and geographical constraints. Based on the issues, several recommendations are proposed for future research using culturally tailored technology-based interventions among racial and ethnic minorities.

Clusters of midlife women identified by cognitive symptoms.

OBJECTIVES: The study aimed to identify clusters of midlife women by their cognitive symptoms and to examine racial/ethnic differences in the clusters. STUDY DESIGN: This secondary analysis was conducted on the data from 1054 midlife women of multi-ethnic groups in two Internet studies (conducted from 2005 to 2013). MAIN OUTCOME MEASURES: Only the data from the questions on background characteristics, health status, and menopausal status and the Cognitive Symptom Index for Midlife Women were used for this secondary analysis. The data were analyzed using factor analyses, hierarchical cluster analyses, chi-square tests, multinomial logistic analyses, and analyses of covariance. RESULTS: Four clusters were extracted: the low total symptom group (Cluster 1; 49.9%), the low-moderate total symptom group with high tertiary symptoms (Cluster 2; 17.3%), the high-moderate total symptom group with low tertiary symptoms (Cluster 3; 21.2%); and the high total symptom group (Cluster 4; 11.7%). There were significant differences in the level of education, employment status, family income, marital status, social support, the country of birth, race/ethnicity, body mass index, perceived general health, diagnosed disease(s), access to health care, and menopausal status among the clusters (p < .01). There were significant racial/ethnic differences in the total numbers and total severity scores of tertiary symptoms in Cluster 1. Also, there were significant racial/ethnic differences in individual symptoms in each cluster. CONCLUSIONS: Racial/ethnic differences in midlife women's cognitive symptoms and multiple factors that might differently influence their cognitive symptoms need to be considered in health care for midlife women in menopausal transition.

The use of multiple languages in a technology-based intervention study: A discussion paper.

BACKGROUND AND OBJECTIVES: With an increasing number of racial/ethnic minorities in the U.S., nursing research frequently involves the use of multiple languages, especially to promote the understanding of educational materials related to nursing care. Furthermore, with a recent emphasis on innovation in health-related research, the use of technology is prominent in nursing research. However, practical issues in the use of multiple languages, especially in technology-based intervention studies, have rarely been reported and/or discussed in nursing literature. The purpose of this paper is to identify practical issues in conducting a technology-based intervention study using multiple languages among Asian American breast cancer survivors. METHODS: In a large-scale technology-based breast cancer intervention study, research team members wrote memos on issues in translation process and plausible reasons for the issues. Then, the memos and written records were analyzed using a content analysis. By using individual words as the unit of analysis, line-by-line coding was done, and idea categories representing practical issues were extracted from the codes. RESULTS: Six themes representing the practical issues were extracted. Issues were found in recruiting and retaining bilingual research team members; maintaining consistency in translation process; keeping cultural and conceptual equivalence; repeating IRB protocol modifications; finding and using existing translated versions; and arranging technological aspects related to electronic multiple-language versions. CONCLUSION: The use of multiple languages in a technology-based intervention study is feasible. However, it is necessary to effectively manage unforeseen challenges through various strategies.

Associations of Immigration Transition to Cardiovascular Symptoms Experienced in Menopausal Transition.

The purpose of this study was to explore the associations of immigration transition to cardiovascular symptoms among 4 major racial/ethnic groups of 1054 midlife women in the United States. This was a secondary analysis of the data from 2 large national survey studies. The instruments included questions on background characteristics and immigration transition and the Cardiovascular Symptom Index for Midlife Women. The data were analyzed using inferential statistics including hierarchical multiple regressions. Immigrants reported fewer numbers (t = 5.268, P < .01) and lower severity scores (t = 5.493, P < .01) of cardiovascular symptoms compared with nonimmigrants. Self-reported racial/ethnic identify was a significant factor influencing cardiovascular symptoms (P < .01).

Midlife women's cardiovascular symptoms: A cluster analysis.

Menopausal transition, in which biological and psychosocial changes are caused due to estrogen fluctuations, has been reported to increase cardiovascular risk among midlife women. The purposes of this study were to identify the clusters of midlife women by cardiovascular symptoms and to examine racial/ethnic differences in the clusters. This was a secondary analysis, in which hierarchical cluster and multinomial logistic analyses were conducted with the data (N = 966) collected in two previous studies. Three clusters were adopted: Cluster 1 (high vasomotor and low cardiorespiratory), Cluster 2 (low vasomotor and high cardiorespiratory and high discomfort/pain), and Cluster 3 (high discomfort/pain and high indigestion).

Improving menopausal symptoms through promoting physical activity: a pilot Web-based intervention study among Asian Americans.

OBJECTIVE: Based on previous studies, a Web-based physical activity promotion program with educational modules on menopausal symptoms and physical activity has been developed for Asian American midlife women to reduce their menopausal symptoms through increasing their physical activity. The purpose of this pilot randomized intervention study was to determine the efficacy of the Web-based program in improving menopausal symptom experience of Asian American midlife women. METHODS: This was a randomized repeated measures pretest/posttest (pretest, post 1 month, and post 3 months) control group study among 29 Asian American midlife women. Multiple instruments were used, including the Midlife Women's Symptom Index and the Kaiser Physical Activity Survey. The data were analyzed using a mixed-model growth curve analysis. RESULTS: Over time, total severity scores decreased for the control group (-0.53, P < 0.10), whereas they did not exhibit a meaningful change for the intervention group. Both study groups experienced improvement in active living habits over time, but such an improvement was greater for the intervention group (ß = 0.29, P < 0.001) than for the control group (ß = 0.08, P < 0.10). The time × group interactions for total severity scores were not statistically significant anymore after controlling for physical activity (-0.34 for the control group, P = 0.10). CONCLUSIONS: The findings supported the feasibility of a 3-month Web-based intervention for menopausal symptom management among Asian American midlife women and the preliminary efficacy of the program in increasing their physical activity.