Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations.

BACKGROUND: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. METHOD: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. RESULTS: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). CONCLUSIONS: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.

Peer support for people living with hepatitis B virus-A foundation for treatment expansion.

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer support to enhance and promote interventions for people living with CHB. Peer support workers (PSWs) are those with lived experience of an infection, condition or situation who work to provide support for others, aiming to improve education, prevention, treatment and other clinical interventions and to reduce the physical, psychological and social impacts of disease. Peer support has been shown to be a valuable tool for improving health outcomes for people living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), but to date has not been widely available for communities affected by HBV. HBV disproportionately affects vulnerable and marginalised populations, who could benefit from PSWs to help them navigate complicated systems and provide advocacy, tackle stigma, improve education and representation, and optimise access to treatment and continuity of care. The scale up of peer support must provide structured and supportive career pathways for PSWs, account for social and cultural needs of different communities, adapt to differing healthcare systems and provide flexibility in approaches to care. Investment in peer support for people living with CHB could increase diagnosis, improve retention in care, and support design and roll out of interventions that can contribute to global elimination goals.

Angle Assessment for Upper Limb Rehabilitation: A Novel Light Detection and Ranging (LiDAR)-Based Approach.

The accurate measurement of joint angles during patient rehabilitation is crucial for informed decision making by physiotherapists. Presently, visual inspection stands as one of the prevalent methods for angle assessment. Although it could appear the most straightforward way to assess the angles, it presents a problem related to the high susceptibility to error in the angle estimation. In light of this, this study investigates the possibility of using a new approach to angle calculation: a hybrid approach leveraging both a camera and LiDAR technology, merging image data with point cloud information. This method employs AI-driven techniques to identify the individual and their joints, utilizing the cloud-point data for angle computation. The tests, considering different exercises with different perspectives and distances, showed a slight improvement compared to using YOLO v7 for angle calculation. However, the improvement comes with higher system costs when compared with other image-based approaches due to the necessity of equipment such as LiDAR and a loss of fluidity during the exercise performance. Therefore, the cost-benefit of the proposed approach could be questionable. Nonetheless, the results hint at a promising field for further exploration and the potential viability of using the proposed methodology.

Complete remissions following immunotherapy or immuno-oncology combinations in cancer patients: the MOUSEION-03 meta-analysis.

BACKGROUND: Immunotherapy has determined unprecedented long-term responses in several hematological and solid tumors. In the MOUSEION-03 study, we conducted a meta-analysis to determine the possibility of achieving complete remissions (CR) with immunotherapy or immuno-oncology combinations in cancer patients. METHODS: The primary endpoint was to assess the incidence of CR in cancer patients receiving immune checkpoint inhibitors (ICIs) alone or in combination with other agents versus control treatments. The pooled odds ratio (OR) and 95% confidence interval (CI) for CR rate were extracted. RESULTS: A total of 12,130 potentially relevant trials were identified; 5 phase II and 80 phase III randomized studies (37 monotherapies and 48 combinations) and 49,425 cancer patients were included. The most frequent types of malignancies were non-small cell lung cancer (n = 14,249; 29%), urothelial cancer (n = 6536; 13%), renal cell carcinoma (n = 5743; 12%), and melanoma (n = 2904; 6%). In patients treated with immunotherapy (as monotherapy or in combination with other anticancer agents), the pooled OR was 1.67 (1.52-1.84). The highest OR was registered by immune-based combinations with two ICIs (3.56, 95% CI 1.28-9.90). CONCLUSIONS: To the best of the authors' knowledge, no comprehensive meta-analysis on the use of ICIs and ICI-based combinations in solid tumors to systematically investigate the probability to achieve CR has been published so far. Although CR is not a common event in several cancer patients receiving immunotherapy, the MOUSEION-03 suggests that the use of ICIs may significantly increase the chance of achieving CR in comparison with control treatments.

Real-world effectiveness of pembrolizumab as first-line therapy for cisplatin-ineligible patients with advanced urothelial carcinoma: the ARON-2 study.

BACKGROUND: The advent of immune-checkpoint inhibitors has challenged previous treatment paradigms for advanced urothelial carcinoma (UC) in the post-platinum setting as well as in the first-line setting for cisplatin-ineligible patients. In this study, we investigated the effectiveness of pembrolizumab as first-line treatment for cisplatin-ineligible UC. METHODS: Data from patients aged ≥ 18 years with cisplatin-ineligible UC and receiving first-line pembrolizumab from January 1st 2017 to September 1st 2022 were collected. Cisplatin ineligibility was defined according to the Galsky criteria. Thirty-three Institutions from 18 countries were involved in the ARON-2 study. RESULTS: Our analysis included 162 patients. The median follow-up time was 18.9 months (95%CI 15.3-76.9). In the overall study population, the median OS was 15.8 months (95%CI 11.3-32.4). The median OS was significantly longer in males versus females while no statistically significant differences were observed between patients aged < 65y versus ≥ 65y and between smokers and non-smokers. According to Recist 1.1 criteria, 26 patients (16%) experienced CR, 32 (20%) PR, 39 (24%) SD and 55 (34%) PD. CONCLUSIONS: Our data confirm the role of pembrolizumab as first-line therapy for cisplatin-unfit patients. Further studies investigating the biological and immunological characteristics of UC patients are warranted in order to optimize the outcome of patients receiving immunotherapy in this setting.

Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.

BACKGROUND: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. METHODS: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. RESULTS: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. CONCLUSIONS: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Molecular and cytogenetic evidence for sibling species in the Chagas disease vector Triatoma maculata.

Triatoma maculata (Hemiptera, Reduviidae, Triatominae) occurs across dry-to-semiarid ecoregions of northern South America, where it transmits Trypanosoma cruzi, causative agent of Chagas disease. Using 207 field-caught specimens from throughout the species' range, mitochondrial(mt) DNA sequence data, and cytogenetics, we investigated inter-population genetic diversity and the phylogenetic affinities of T. maculata. Mitochondrial DNA sequence analyses (cytb and nd4) disclosed a monophyletic T. maculata clade encompassing three distinct geographic groups: Roraima formation (Guiana shield), Orinoco basin, and Magdalena basin (trans-Andean). Between-group cytb distances (11.0-12.8%) were larger than the ~7.5% expected for sister Triatoma species; the most recent common ancestor of these T. maculata groups may date back to the late Miocene. C-heterochromatin distribution and the sex-chromosome location of 45S ribosomal DNA clusters both distinguished Roraima bugs from Orinoco and Magdalena specimens. Cytb genealogies reinforced that T. maculata is not sister to Triatoma pseudomaculata and probably represents an early (middle-late Miocene) offshoot of the 'South American Triatomini lineage'. In sum, we report extensive genetic diversity and deep phylogeographic structuring in T. maculata, suggesting that it may consist of a complex of at least three sibling taxa. These findings have implications for the systematics, population biology, and perhaps medical relevance of T. maculata sensu lato.

Interactions between Dental MSCs and Biomimetic Composite Scaffold during Bone Remodeling Followed by In Vivo Real-Time Bioimaging.

Oral-maxillofacial tumor removal can generate critical bone defects and major problems for patients, causing dysfunctionalities and affecting oral competencies such as mastication, swallowing, and breathing. The association of novel biomaterials and cell therapies in tissue engineering strategies could offer new strategies to promote osteomucosa healing. This study focused on the development of a bioengineered construct loaded with human dental follicle cells (MSCs). To increase the bioconstruct integration to the surrounding tissue, a novel and comprehensive approach was designed combining an injectable biomimetic hydrogel and dental stem cells (hDFMSCs) expressing luminescence/fluorescence for semi-quantitative tissue imaging in live animals. This in vivo model with human MSCs was based on an intramembranous bone regeneration process (IMO). Biologically, the biocomposite based on collagen/nanohydroxyapatite filled with cell-loaded osteopontin-fibrin hydrogel (Coll/nanoHA OPN-Fb) exhibited a high cellular proliferation rate, increased bone extracellular matrix deposition (osteopontin) and high ALP activity, indicating an early osteogenic differentiation. Thus, the presence of human OPN enhanced hDFMSC adhesion, migration, and spatial distribution within the 3D matrix. The developed 3D bioconstruct provided the necessary pro-regenerative effect to modulate the biological response, precisely fitting the bone defect with fine-tuned adjustment to the surrounding original structure and promoting oral osteomucosa tissue regeneration. We were also able to track the cells in vivo and evaluate their behavior (migration, proliferation, and differentiation), providing a glimpse into bone regeneration and helping in the optimization of patient-specific therapies.

A Comprehensive Look at In Vitro Angiogenesis Image Analysis Software.

One of the complex challenges faced presently by tissue engineering (TE) is the development of vascularized constructs that accurately mimic the extracellular matrix (ECM) of native tissue in which they are inserted to promote vessel growth and, consequently, wound healing and tissue regeneration. TE technique is characterized by several stages, starting from the choice of cell culture and the more appropriate scaffold material that can adequately support and supply them with the necessary biological cues for microvessel development. The next step is to analyze the attained microvasculature, which is reliant on the available labeling and microscopy techniques to visualize the network, as well as metrics employed to characterize it. These are usually attained with the use of software, which has been cited in several works, although no clear standard procedure has been observed to promote the reproduction of the cell response analysis. The present review analyzes not only the various steps previously described in terms of the current standards for evaluation, but also surveys some of the available metrics and software used to quantify networks, along with the detection of analysis limitations and future improvements that could lead to considerable progress for angiogenesis evaluation and application in TE research.

Robot-Assisted Rehabilitation Architecture Supported by a Distributed Data Acquisition System.

Rehabilitation robotics aims to facilitate the rehabilitation procedure for patients and physical therapists. This field has a relatively long history dating back to the 1990s; however, their implementation and the standardisation of their application in the medical field does not follow the same pace, mainly due to their complexity of reproduction and the need for their approval by the authorities. This paper aims to describe architecture that can be applied to industrial robots and promote their application in healthcare ecosystems. The control of the robotic arm is performed using the software called SmartHealth, offering a 2 Degree of Autonomy (DOA). Data are gathered through electromyography (EMG) and force sensors at a frequency of 45 Hz. It also proves the capabilities of such small robots in performing such medical procedures. Four exercises focused on shoulder rehabilitation (passive, restricted active-assisted, free active-assisted and Activities of Daily Living (ADL)) were carried out and confirmed the viability of the proposed architecture and the potential of small robots (i.e., the UR3) in rehabilitation procedure accomplishment. This robot can perform the majority of the default exercises in addition to ADLs but, nevertheless, their limits were also uncovered, mainly due to their limited Range of Motion (ROM) and cost.

Bioengineering Approaches to Fight against Orthopedic Biomaterials Related-Infections.

One of the most serious complications following the implantation of orthopedic biomaterials is the development of infection. Orthopedic implant-related infections do not only entail clinical problems and patient suffering, but also cause a burden on healthcare care systems. Additionally, the ageing of the world population, in particular in developed countries, has led to an increase in the population above 60 years. This is a significantly vulnerable population segment insofar as biomaterials use is concerned. Implanted materials are highly susceptible to bacterial and fungal colonization and the consequent infection. These microorganisms are often opportunistic, taking advantage of the weakening of the body defenses at the implant surface-tissue interface to attach to tissues or implant surfaces, instigating biofilm formation and subsequent development of infection. The establishment of biofilm leads to tissue destruction, systemic dissemination of the pathogen, and dysfunction of the implant/bone joint, leading to implant failure. Moreover, the contaminated implant can be a reservoir for infection of the surrounding tissue where microorganisms are protected. Therefore, the biofilm increases the pathogenesis of infection since that structure offers protection against host defenses and antimicrobial therapies. Additionally, the rapid emergence of bacterial strains resistant to antibiotics prompted the development of new alternative approaches to prevent and control implant-related infections. Several concepts and approaches have been developed to obtain biomaterials endowed with anti-infective properties. In this review, several anti-infective strategies based on biomaterial engineering are described and discussed in terms of design and fabrication, mechanisms of action, benefits, and drawbacks for preventing and treating orthopaedic biomaterials-related infections.

New prospects in skin regeneration and repair using nanophased hydroxyapatite embedded in collagen nanofibers.

This study reflects an exploitation of a composite matrix produced by electrospinning of collagen and electrospraying of nanophased hydroxyapatite (nanoHA), for skin regeneration applications. The main goal was to evaluate the effect of nanoHA, as source of localized calcium delivery, on human dermal fibroblasts, keratinocytes, and human mesenchymal stem cells (hMSCs) growth, proliferation, differentiation, and extracellular matrix production. This study revealed that calcium ions provided by nanoHA significantly enhanced cellular growth and proliferation rates and prevented adhesion of pathogenic bacteria strains typically found in human skin flora. Moreover, hMSCs were able to differentiate in both osteogenic and adipogenic lineages. Rat subcutaneous implantation of the membranes also revealed that no adverse reaction occurred. Therefore, the mechanically fit composite membrane presents a great potential to be used either as cell transplantation scaffold for skin wound regeneration or as wound dressing material in plastic surgery, burns treatment or skin diseases.

Consensus on diagnosis and management of non-metastatic castration resistant prostate cancer in Brazil: focus on patient, selection, treatment efficacy, side effects and physician's perception according to patient comorbidities.

BACKGROUND: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. OBJECTIVE: To present survey results on management of M0 CRPC in Brazil. DESIGN, SETTING, AND PARTICIPANTS: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. CONCLUSIONS: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.

Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma: How to Apply New Evidence in Clinical Practice.

Cytoreductive nephrectomy (CN) followed by systemic therapy had been considered the standard of care for metastatic renal cell carcinoma (mRCC) patients since two clinical trials established its role during the cytokines era. With introduction of new and effective drugs, such as vascular endothelial growth factor-targeted therapies, the role of CN started to be challenged. Retrospective studies conducted during the targeted therapy era pointed to better outcomes when CN was associated with systemic treatment, although certain patients with poor risk features did not seem to benefit. Therefore, prospective clinical trials supporting CN were needed. Recently, with the publication of two randomized trials evaluating CN in the targeted therapy era, it has been made clear that patient selection and multidisciplinary discussion are of paramount importance in order to achieve the best outcomes. We reviewed the available literature on the role of CN among mRCC patients, commenting on how to apply the new evidence into clinical practice and providing future perspectives.

Search for Composite Dark Matter with Optically Levitated Sensors.

Results are reported from a search for a class of composite dark matter models with feeble long-range interactions with normal matter. We search for impulses arising from passing dark matter particles by monitoring the mechanical motion of an optically levitated nanogram mass over the course of several days. Assuming such particles constitute the dominant component of dark matter, this search places upper limits on their interaction with neutrons of α_{n}≤1.2×10^{-7} at 95% confidence for dark matter masses between 1 and 10 TeV and mediator masses m_{ϕ}≤0.1 eV. Because of the large enhancement of the cross section for dark matter to coherently scatter from a nanogram mass (∼10^{29} times that for a single neutron) and the ability to detect momentum transfers as small as ∼200 MeV/c, these results provide sensitivity to certain classes of composite dark matter models that substantially exceeds existing searches, including those employing kilogram- or ton-scale targets. Extensions of these techniques can enable directionally sensitive searches for a broad class of previously inaccessible heavy dark matter candidates.

Encapsulated bacteriophages in alginate-nanohydroxyapatite hydrogel as a novel delivery system to prevent orthopedic implant-associated infections.

An innovative delivery system based on bacteriophages-loaded alginate-nanohydroxyapatite hydrogel was developed as a multifunctional approach for local tissue regeneration and infection prevention and control. Bacteriophages were efficiently encapsulated, without jeopardizing phage viability and functionality, nor affecting hydrogel morphology and chemical composition. Bacteriophage delivery occurred by swelling-disintegration-degradation process of the alginate structure and was influenced by environmental pH. Good tissue response was observed following the implantation of bacteriophages-loaded hydrogels, sustaining their biosafety profile. Bacteriophages-loaded hydrogels did not affect osteoblastic cells' proliferation and morphology. A strong osteogenic and mineralization response was promoted through the implantation of hydrogels system with nanohydroxyapatite. Lastly, bacteriophages-loaded hydrogel showed excellent antimicrobial activity inhibiting the attachment and colonization of multidrug-resistant E. faecalis surrounding and within femoral tissues. This new local delivery approach could be a promising approach to prevent and control bacterial contamination during implantation and bone integration.

Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection.

Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.

Antibacterial silk fibroin/nanohydroxyapatite hydrogels with silver and gold nanoparticles for bone regeneration.

The rapid emergence of antibiotic resistance is becoming an imminent problem in bone tissue engineering, and therefore biomaterials must be modified to promote the tissue integration before bacterial adhesion. In this work, silk fibroin/nanohydroxyapatite hydrogel was modified with in situ synthesized silver and gold nanoparticles (AgNPs and AuNPs), taking advantage of the tyrosine amino acid. The presence of AgNPs and AuNPs in the hydrogels was characterized by UV spectrophotometer, transmission electron microscopy and thermogravimetric analysis. In vitro antimicrobial studies revealed that hydrogels with AgNPs and AuNPs exhibited significant inhibition ability against both gram-positive and gram-negative bacteria. Cytocompatibility studies carried out using osteoblastic cells revealed that up to 0.5 wt% of AgNPs, and for all concentrations of AuNPs, the hydrogels can be effectively used as antimicrobial materials, without compromising cell behavior. On the basis of the aforementioned observations, these hydrogels are very attractive for bone tissue engineering.

Enhanced biosafety of silica coated gadolinium based nanoparticles.

One of the most important and novel approaches of biomedical engineering is the development of new, effective and non-invasive medical diagnosis abilities, and treatments that have such requirements as advanced technologies for tumor imaging. Gadolinium (Gd) compounds can be used as MRI contrast agents, however the release of Gd3+ ions presents some adverse side effects such as renal failure, pancreatitis or local necrosis. The main aim of the work was the development and optimization of Gadolinium based nanoparticles coated with silica to be used as bioimaging agent. Gd based nanoparticles were prepared through a precipitation method and afterwards, these nanoparticles were covered with silica, using Stöber method with ammonia and functionalized with 3-Aminopropyltriethoxysilane (APTES). Results showed that nanoparticles were homogeneous regarding chemical composition, silica layer thickness, total size and morphology. Also, silica coating was successfully not degraded after 4 weeks at pH 5.5, 6.0 and 7.4, contrary to GdOHCO3 nanoparticles that degraded. Regarding the in vitro cell tests, very good cell proliferation and viability were observed. In conclusion, the results showed that Gd based nanoparticles coated with silica for imaging applications were successfully obtained under a well-controlled method. Furthermore, silica coating may enhance magnetic nanoparticles biosafety because it avoids GdOHCO3 degradation into harmful products (such as Gd3+ ions) at physiological conditions.

Phase Behaviour and Miscibility Studies of Collagen/Silk Fibroin Macromolecular System in Dilute Solutions and Solid State.

Miscibility is an important issue in biopolymer blends for analysis of the behavior of polymer pairs through the detection of phase separation and improvement of the mechanical and physical properties of the blend. This study presents the formulation of a stable and one-phase mixture of collagen and regenerated silk fibroin (RSF), with the highest miscibility ratio between these two macromolecules, through inducing electrostatic interactions, using salt ions. For this aim, a ternary phase diagram was experimentally built for the mixtures, based on observations of phase behavior of blend solutions with various ratios. The miscibility behavior of the blend solutions in the miscible zones of the phase diagram was confirmed quantitatively by viscosimetric measurements. Assessing the effects of biopolymer mixing ratio and salt ions, before and after dialysis of blend solutions, revealed the importance of ion-specific interactions in the formation of coacervate-based materials containing collagen and RSF blends that can be used in pharmaceutical, drug delivery, and biomedical applications. Moreover, the conformational change of silk fibroin from random coil to beta sheet, in solution and in the final solid films, was detected by circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), respectively. Scanning electron microscopy (SEM) exhibited alterations of surface morphology for the biocomposite films with different ratios. Surface contact angle measurement illustrated different hydrophobic properties for the blended film surfaces. Differential scanning calorimetry (DSC) showed that the formation of the beta sheet structure of silk fibroin enhances the thermal stability of the final blend films. Therefore, the novel method presented in this study resulted in the formation of biocomposite films whose physico-chemical properties can be tuned by silk fibroin conformational changes by applying different component mixing ratios.