Advancement in Biopolymer Assisted Cancer Theranostics.

Applications of nanotechnology have increased the importance of research and nanocarriers, which have revolutionized the method of drug delivery to treat several diseases, including cancer, in the past few years. Cancer, one of the world's fatal diseases, has drawn scientists' attention for its multidrug resistance to various chemotherapeutic drugs. To minimize the side effects of chemotherapeutic agents on healthy cells and to develop technological advancement in drug delivery systems, scientists have developed an alternative approach to delivering chemotherapeutic drugs at the targeted site by integrating it inside the nanocarriers like synthetic polymers, nanotubes, micelles, dendrimers, magnetic nanoparticles, quantum dots (QDs), lipid nanoparticles, nano-biopolymeric substances, etc., which has shown promising results in both preclinical and clinical trials of cancer management. Besides that, nanocarriers, especially biopolymeric nanoparticles, have received much attention from researchers due to their cost-effectiveness, biodegradability, treatment efficacy, and ability to target drug delivery by crossing the blood-brain barrier. This review emphasizes the fabrication processes, the therapeutic and theragnostic applications, and the importance of different biopolymeric nanocarriers in targeting cancer both in vitro and in vivo, which conclude with the challenges and opportunities of future exploration using biopolymeric nanocarriers in onco-therapy with improved availability and reduced toxicity.

Antibody-Biopolymer Conjugates in Oncology: A Review.

Cancer is one of the most prevalent diseases and affects a large proportion of the population worldwide. Conventional treatments in the management include chemotherapy, radiotherapy, and surgery. Although being well-accepted, they have many lacunas in the form of severe side effect resulting from lack of targeted delivery. Antibody biopolymer conjugates are a novel method which is an add-on to older methods of immunization. It is used in various diseases and disorders. It ensures the targeted delivery of molecules to increase its efficacy and reduce unwanted effects of the molecule/drug to normal cells. It shows miraculous results in the treatment and management of several cancers even in advanced stages. Herein, we present the chemistry between biopolymer and antibody, their effects on cancer as well as the basic differences between antibody-drug conjugates and antibody-biopolymer conjugates.

Cicatrization of oncological wounds by autologous fibrin biopolymer dressing treatment: a case series.

INTRODUCTION: Traditional therapies used to treat chronic wounds are often expensive and, in general, are not adequate to support healing. A promising alternative to conventional dressings is the autologous biopolymer FM, full of cytokines and growth factors that accelerate the healing process of wounds of various etiologies. MATERIALS AND METHODS: The authors report 3 cases in which FM was used to treat chronic oncological wounds that had been conventionally treated for more than 6 months with no sign of healing. RESULTS: Among the 3 reported cases, there was complete healing of 2 wounds. The other lesion did not heal, mainly due to the location (at the base of the skull). However, it significantly reduced its area, extension, and depth. No adverse effects or hypertrophic scar formation were recorded, and the patients reported an absence of pain from the second week of FM application. CONCLUSIONS: The proposed FM dressing approach was effective in healing and speeding up tissue regeneration. It can also be considered one of the most versatile delivery systems to the wound bed, as it is an excellent carrier of growth factors and leukocytes.

Eletrofiação aplicada a cicatrização de feridas: revisão de literatura / Electrospinning applied to wound healing: literature review / Electroalambre aplicado a la cicatrización de heridas: revisión de la literatura

feridas correspondem a interrupção da continuidade da pele, com a perda de uma ou mais camadas do tecido cutâneo. Curativos tradicionalmente aplicados em feridas cutâneas buscam principalmente fornecer uma barreira de proteção e permitir o desenvolvimento dos eventos celulares e bioquímicos que compreendem a cicatrização. Objetivou-se com este estudo apresentar sob a forma de revisão de literatura narrativa os principais eventos relacionados ao processo de reparo tecidual da pele, bem como abordar a aplicabilidade da técnica de eletrofiação no desenvolvimento de curativos funcionais biocompatíveis. Foram selecionados artigos voltados à caracterização dos eventos chave ocorridos a nível tecidual durante a cicatrização e, na sequência, buscou-se artigos voltados à produção, caracterização e aplicação de filmes nanoeletrofiados com ênfase na utilização de biopolímeros e substâncias bioativas. Observou-se que a maioria dos trabalhos recentes, voltados a pesquisa de base, descrevem a resposta vascular como o principal evento do processo cicatricial, sendo responsável pelas etapas que se desenrolam a seguir, que compreendem as fases inflamatória, proliferativa e de remodelamento, classicamente já descritas. Os curativos funcionais baseados em polímeros eletrofiados apresentam resultados superiores quanto testados in vitro e in vivo. As características morfoestruturais mimetizam a matriz extracelular e podem atuar em tecidos alvo como dispositivos de entrega de substâncias. Conclui-se que a atualização e reorganização de conceitos relativos à cicatrização podem contribuir no desenvolvimento de inovações, como os curativos produzidos por eletrofiação. Embora promissora, as desvantagens da técnica encontram-se principalmente no processo de obtenção e disponibilidade, que limitam a aplicação clínica em escala comercial.

Wounds correspond to the interruption of skin continuity, with the loss of one or more layers of skin tissue. Dressings traditionally applied to cutaneous wounds mainly seek to provide a protective barrier and allow the development of cellular and biochemical events that comprise healing. The objective of this study was to present, in the form of a narrative literature review, the main events related to the skin tissue repair process, as well as to address the applicability of the electrospinning technique in the development of biocompatible functional dressings. Articles focused on the characterization of the key events that occurred at the tissue level during healing were selected and, subsequently, articles focused on the production, characterization and application of nanoelectrospun films with emphasis on the use of biopolymers and bioactive substances were sought. It was observed that most recent works, focused on basic research, describe the vascular response as the main event of the healing process, being responsible for the steps that follow, which include the inflammatory, proliferative and remodeling phases, classically already described. Functional dressings based on electrospun polymers show superior results when tested in vitro and in vivo. The morphostructural features mimic the extracellular matrix and can act in target tissues as substance delivery devices. It is concluded that the updating and reorganization of concepts related to healing can contribute to the development of innovations, such as dressings produced by electrospinning. Although promising, the technique's disadvantages lie mainly in the process of obtaining and availability, which limit clinical application on a commercial scale.

Las heridas corresponden a la interrupción de la continuidad de la piel, con la pérdida de una o más capas de tejido cutáneo. Los apósitos aplicados tradicionalmente a las heridas cutáneas buscan principalmente proporcionar una barrera protectora y permitir el desarrollo de los eventos celulares y bioquímicos que comprenden la curación. El objetivo de este estudio fue presentar en forma de revisión bibliográfica narrativa los principales acontecimientos relacionados con el proceso de reparación tisular de la piel, así como abordar la aplicabilidad de la técnica de electrodeposición en el desarrollo de apósitos funcionales biocompatibles. Se seleccionaron artículos dirigidos a la caracterización de los eventos chave ocurridos a nivel técnico durante la cicatrización y, a continuación, se buscaron artículos dirigidos a la producción, caracterización y aplicación de películas nanoelectrofíricas con énfasis en el uso de biopolímeros y sustancias bioativas. Se observa que la mayoría de los trabajos recientes, realizados en la investigación de base, describen la respuesta vascular como el principal evento del proceso cicatricial, siendo responsable de las etapas que se desarrollan a continuación, que comprenden las fases inflamatoria, proliferativa y de remodelación, clásicamente descritas. Los apósitos funcionales basados en polímeros electro-tejidos presentan resultados superiores cuando se prueban in vitro e in vivo. Las características morfoestruturales mimetizan la matriz extracelular y pueden actuar en tejidos alvos como dispositivos de entrega de sustancias. Se concluye que la actualización y la reorganización de los conceptos relativos a la cicatrización pueden contribuir al desarrollo de innovaciones, como las curativas producidas por la electrofagia. Aunque es prometedora, las desventajas de la técnica radican principalmente en el proceso de obtención y la disponibilidad, que limitan la aplicación clínica a escala comercial.

KSI-301: an investigational anti-VEGF biopolymer conjugate for retinal diseases.

INTRODUCTION: KSI-301 is an intravitreal anti-vascular endothelial growth factor (VEGF) agent in clinical trials for the treatment of neovascular age-related macular degeneration (nAMD), diabetic retinopathy, diabetic macular edema (DME), and retinal vein occlusion (RVO). Its antibody-biopolymer conjugate structure is designed to decrease clearance from the eye and increase the duration of the effect. AREAS COVERED: This article briefly discusses the impact and mechanisms of nAMD, DME, and RVO and evaluates currently approved anti-VEGF therapies. It progresses to examine a new agent, KSI-301 and the results from numerous clinical trials in these disease areas. EXPERT OPINION: Despite varied results in the phase 2b/3 study for nAMD, there is potential for KSI-301 to serve as a durable therapy for VEGF-mediated retinal disorders. Ongoing phase 3 trials for nAMD, DME, and RVO will provide additional evidence on its efficacy, duration, and safety profiles.

Lignin, lipid, protein, hyaluronic acid, starch, cellulose, gum, pectin, alginate and chitosan-based nanomaterials for cancer nanotherapy: Challenges and opportunities.

Although nanotechnology-driven drug delivery systems are relatively new, they are rapidly evolving since the nanomaterials are deployed as effective means of diagnosis and delivery of assorted therapeutic agents to targeted intracellular sites in a controlled release manner. Nanomedicine and nanoparticulate drug delivery systems are rapidly developing as they play crucial roles in the development of therapeutic strategies for various types of cancer and malignancy. Nevertheless, high costs, associated toxicity and production of complexities are some of the critical barriers for their applications. Green nanomedicines have continually been improved as one of the viable approaches towards tumor drug delivery, thus making a notable impact on which considerably affect cancer treatment. In this regard, the utilization of natural and renewable feedstocks as a starting point for the fabrication of nanosystems can considerably contribute to the development of green nanomedicines. Nanostructures and biopolymers derived from natural and biorenewable resources such as proteins, lipids, lignin, hyaluronic acid, starch, cellulose, gum, pectin, alginate, and chitosan play vital roles in the development of cancer nanotherapy, imaging and management. This review uncovers recent investigations on diverse nanoarchitectures fabricated from natural and renewable feedstocks for the controlled/sustained and targeted drug/gene delivery systems against cancers including an outlook on some of the scientific challenges and opportunities in this field. Various important natural biopolymers and nanomaterials for cancer nanotherapy are covered and the scientific challenges and opportunities in this field are reviewed.

SuperGAG biopolymers for treatment of excessive bladder permeability.

Few therapeutic options exist for treatment of IC/BPS. A novel high MW GAG biopolymer ("SuperGAG") was synthesized by controlled oligomerization of CS, purified by TFF and characterized by SEC-MALLS and 1H-NMR spectroscopy. The modified GAG biopolymer was tested in an OVX female rat model in which bladder permeability was induced by a 10-minute intravesicular treatment with dilute (1 mg/ml) protamine sulfate and measured by classical Ussing Chamber TEER measurements following treatment with SuperGAG, chondroitin sulfate, or saline. The effect on abrogating the abdominal pain response was assessed using von Frey filaments. The SuperGAG biopolymer was then investigated in a second, genetically modified mouse model (URO-MCP1) that increasingly is accepted as a model for IC/BPS. Permeability was induced with a brief exposure to a sub-noxious dose of LPS and was quantified using contrast-enhanced MRI (CE-MRI). The SuperGAG biopolymer restored impermeability to normal levels in the OVX rat model as measured by TEER in the Ussing chamber and reduced the abdominal pain response arising from induced permeability. Evaluation in the URO-MCP1 mouse model also showed restoration of bladder impermeability and showed the utility of CE-MRI imaging for evaluating the efficacy of agents to restore bladder impermeability. We conclude novel high MW SuperGAG biopolymers are effective in restoring urothelial impermeability and reducing pain produced by loss of the GAG layer on the urothelium. SuperGAG biopolymers could offer a novel and effective new therapy for IC/BPS, particularly if combined with MRI to assess the efficacy of the therapy.

Chitosan and gelatin biopolymer supplemented with mesenchymal stem cells (Velgraft®) enhanced wound healing in goats (Capra hircus): Involvement of VEGF, TGF and CD31.

AIM: Cell-based therapy has emerged as promising strategy for chronic and impaired wounds treatment. Current research is focused on developing biomaterial systems that act as a niche for mesenchymal stem cells (MSCs) to promote wound healing through paracrine molecular cascading. This study was aimed to evaluate the wound healing potential of Velgraft, a ready-to-use biodegradable artificial skin substitute, on excision wound in goats. MATERIALS AND METHODS: Twelve male goats were randomized divided in to three groups of four animals each. After infliction of surgical wound, Velgraft and Soframycin were applied on wounds of the animals of Groups II and III while Group I (sham operated) served as control. Wound diameters were measured at pre-defined time-points for determination of progressive wound healing up to 28 days. Skin sections were stained using Hematoxylin and eosin (H&E) for examining the histoarchitectural changes, Masson trichome staining for ascertaining collagen synthesis and immunohistochemistry for expression of CD31, VEGF and TGF-ß1 proteins to determine post-treatment angiogenesis in the inflicted wounds. RESULTS: Velgraft application appreciably enhanced wound closure by day 21 which was confirmed through restoration of the normal skin architecture as evident based on histopathological examination and characterized by complete regeneration of epidermal layers, collagen fibers, blood capillaries and hair follicular formation. Stimulation of angiogenesis markers was also observed at different time-points post-Velgraft application; which is suggestive of the improved angiogenesis and vasculogenesis. CONCLUSION: Velgraft facilitates wound healing by augmenting early wound closure, enhancing collagen synthesis and deposition, trichosis development and promoting revascularization and epidermal layers restoration.

Biopolymer Immune Implants' Sequential Activation of Innate and Adaptive Immunity for Colorectal Cancer Postoperative Immunotherapy.

Surgical resection is the first-line therapy for colorectal cancer (CRC). However, for advanced CRC, the curative effect of surgical resection is limited due to either local recurrence or distal metastasis. Postoperative in situ immunotherapy, presents a promising option for preventing tumor recurrence and metastasis, owing to the fact that surgeons have unique opportunities and direct access to the surgical site. Herein, a designed biopolymer immune implant for CRC post-surgical therapy, characterized with tissue adhesion, sustained drug release, and sequential elicitation of innate immunity, adaptive immunity, and immune memory effects, is reported. With gradual release of the loaded resiquimod (R848) and anti-OX40 antibody (aOX40), the immune implant can eradicate residual tumors post-surgery (with no tumor recurrence in 150 days), inhibit the growth of distal tumors and elicit immune memory effects to resist tumor re-challenge. Immunological analysis reveal that the biopolymer immune plant treatment leads to a two-stage action, with enhanced natural killer cells (NK cells) infiltration and activation of dendritic cells (DCs) in the first several days, then a greatly increased population of infiltrating T cells, and finally immune memory effects are established. The reported biopolymer immune implants provide a valuable and clinically-relevant option for post-surgical CRC management.

Production, characterization and application of nanocarriers made of polysaccharides, proteins, bio-polyesters and other biopolymers: A review.

Chitosan, collagen, gelatin, polylactic acid and polyhydroxyalkanoates are notable examples of biopolymers, which are essentially bio-derived polymers produced by living cells. With the right techniques, these biological macromolecules can be exploited for nanotechnological advents, including for the fabrication of nanocarriers. In the world of nanotechnology, it is highly essential (and optimal) for nanocarriers to be biocompatible, biodegradable and non-toxic for safe in vivo applications, including for drug delivery, cancer immunotherapy, tissue engineering, gene delivery, photodynamic therapy and many more. The recent advancements in understanding nanotechnology and the physicochemical properties of biopolymers allows us to modify biological macromolecules and use them in a multitude of fields, most notably for clinical and therapeutic applications. By utilizing chitosan, collagen, gelatin, polylactic acid, polyhydroxyalkanoates and various other biopolymers as synthesis ingredients, the 'optimal' properties of a nanocarrier can easily be attained. With emphasis on the aforementioned biological macromolecules, this review presents the various biopolymers utilized for nanocarrier synthesis along with their specific synthetization methods. We further discussed on the characterization techniques and related applications for the synthesized nanocarriers.

Multiplex bioassaying of cancer proteins and biomacromolecules: Nanotechnological, structural and technical perspectives.

Since the specific proteins (carbohydrate antigens, ligands and interleukins) get raised up in body tissue or fluids in cancer cases, early detection of them will provide an effective treatment and survival rate. Sensitive and accurate determination of multiple cancer proteins can be engaged in chorus by simultaneous/multiplex detection in the biomedical fields. Bioassaying technology is one of the non-invasive, high-sensitive, and economical methods. Currently, extensive application of nanomaterial (biocompatible polymers, metallic and metal oxide) in bioassays resulted in ultra-high sensitive and selective diagnosis. This review article focuses on types of multiplex bioassays for delicate and specific determination of cancer proteins for diagnostic aims. It also covers two modes of multiplex bioassays as multi labeled bioassays and spatially-separated test zones (multi-electrode mode). In this review, the nanotechnological, structural, and technical perspectives in the multiplex analysis of cancer proteins were discussed. Finally, the use of different types of nanomaterials, polysaccharides, biopolymers and their advantages in signal amplification are discussed.

A dual-functional Embolization-Visualization System for Fluorescence image-guided Tumor Resection.

Rationale: Intraoperative bleeding impairs physicians' ability to visualize the surgical field, leading to increased risk of surgical complications and reduced outcomes. Bleeding is particularly challenging during endoscopic-assisted surgical resection of hypervascular tumors in the head and neck. A tool that controls bleeding while marking tumor margins has the potential to improve gross tumor resection, reduce surgical morbidity, decrease blood loss, shorten procedure time, prevent damage to surrounding tissues, and limit postoperative pain. Herein, we develop and characterize a new system that combines pre-surgical embolization with improved visualization for endoscopic fluorescence image-guided tumor resection. Methods: Silk-elastinlike protein (SELP) polymers were employed as liquid embolic vehicles for delivery of a clinically used near-infrared dye, indocyanine green (ICG). The biophysical properties of SELP, including gelation kinetics, modulus of elasticity, and viscosity, in response to ICG incorporation using rheology, were characterized. ICG release from embolic SELP was modeled in tissue phantoms and via fluorescence imaging. The embolic capability of the SELP-ICG system was then tested in a microfluidic model of tumor vasculature. Lastly, the cytotoxicity of the SELP-ICG system in L-929 fibroblasts and human umbilical vein endothelial cells (HUVEC) was assessed. Results: ICG incorporation into SELP accelerated gelation and increased its modulus of elasticity. The SELP embolic system released 83 ± 8% of the total ICG within 24 hours, matching clinical practice for pre-surgical embolization procedures. Adding ICG to SELP did not reduce injectability, but did improve the gelation kinetics. After simulated embolization, ICG released from SELP in tissue phantoms diffused a sufficient distance to deliver dye throughout a tumor. ICG-loaded SELP was injectable through a clinical 2.3 Fr microcatheter and demonstrated deep penetration into 50-µm microfluidic-simulated blood vessels with durable occlusion. Incorporation of ICG into SELP improved biocompatibility with HUVECs, but had no effect on L-929 cell viability. Principle Conclusions: We report the development and characterization of a new, dual-functional embolization-visualization system for improving fluorescence-imaged endoscopic surgical resection of hypervascular tumors.

P-mapa, a promisor immunomodulator against tumor cells of colonic tissues: An investigation of the action mechanism over the TLR4 signaling pathway.

Colorectal cancer (CRC) is a multifactorial syndrome that drives to uncontrollable cell division, genetic alterations, and functional alteration. In the present work, we evaluated the immunomodulatory properties of P-mapa, a compound extracted from Aspergillus oryzae fungus, versus Fluorouracil (5-FU) treatment in chemically induced CRC. CRC was induced by DMH in F344 rats. Animals of treated groups receive weekly 15 mg/Kg of 5-FU or 5 mg/Kg of P-mapa, over 10 weeks. Tissues were stained for aberrant crypt foci (ACF) counting and histopathology evaluation, immunostained for TLR4 pathways and quantified for TNFα Cytokine assay. DMH was efficient to induce hyperplastic lesions and ACF. Both treatments reduced significantly ACF formation and tumor aggressiveness. Immunohistochemistry for TLR4 signaling reveals that both treatments had no effect over the TLR4-NFκB signaling pathway. On the other hand, both succeed in increase interferon signaling, with activation of the TRIF-IRF3 pathway and consequently inducing IFNγ synthesis. The present results show the immunomodulatory properties of P-mapa in chemically induced CRC model. P-mapa induced a significant increase in Type-I IFNs synthesis and subsequently immune cell recruitment, resulting in an increase of IFNγ concentration in colorectal mucosa and its inhibitory effects over tumoral growth. In this scenario, P-mapa showed an interesting antitumoral effect by inhibiting tumor growth.

Bacterial cellulose biopolymer film and gel dressing for the treatment of ischemic wounds after lower limb revascularization. / Curativo com filme e gel de biopolímero de celulose bacteriana no tratamento de feridas isquêmicas após revascularização de membros inferiores.

OBJECTIVE: to evaluate the use of a bacterial cellulose biopolymer film and gel dressing in the treatment of patients with ischemic wounds submitted to lower limb revascularization. METHODS: we conducted a randomized clinical trial in the Angiology and Vascular Surgery outpatient clinic of the Clinics Hospital of the Federal University of Pernambuco, between January 2017 and December 2018. We followed 24 patients after lower limb revascularization, divided into two groups: Experimental, treated with bacterial cellulose biopolymer film and gel, and Control, treated with essential fatty acids. Patients attended weekly appointments to change dressings and had their wound healing processes evaluated over a period of 90 days. RESULTS: the reduction of the ischemic wounds' areas after 30 days was 4.3cm2 (55%) on average for the experimental group, and the 5.5cm2 (48.5%) for the control group (p>0.05). The complete healing rate at 90 days was 34.8%, 50% in the experimental group and 18.2% in the control group (p=0.053). CONCLUSION: the bacterial cellulose biopolymer film associated with gel can be used as a dressing in the treatment of ischemic wounds of patients undergoing revascularization of the lower limbs.

OBJETIVO: avaliar o uso do curativo de filme e gel de biopolímero de celulose bacteriana no tratamento de pacientes com feridas isquêmicas submetidos à revascularização dos membros inferiores. MÉTODOS: ensaio clínico randomizado realizado no ambulatório de Angiologia e Cirurgia Vascular do Hospital das Clínicas da Universidade Federal de Pernambuco, entre janeiro de 2017 e dezembro de 2018. Foram acompanhados 24 pacientes após revascularização de membros inferiores, divididos em dois grupos: Experimental, tratado com filme e gel de biopolímero de celulose bacteriana, e Controle, tratado com ácidos graxos essenciais. Os pacientes foram acompanhados em consultas semanais para troca dos curativos e o processo de cicatrização das feridas foi avaliado em um período de 90 dias. RESULTADOS: a redução da área das feridas isquêmicas no período de 30 dias foi de 4,3cm2 (55%), em média, para o grupo experimental, e de 5,5cm2 (48,5%) para o grupo controle (p>0,05). A taxa de cicatrização completa, em 90 dias, foi de 34,8%, sendo 50% no grupo experimental e 18,2% no grupo controle (p=0,053). CONCLUSÃO: o filme de biopolímero de celulose bacteriana associada a gel pode ser utilizado como curativo no tratamento de feridas isquêmicas de pacientes submetidos à revascularização de membros inferiores.

A strongly adhesive hemostatic hydrogel for the repair of arterial and heart bleeds.

Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60-160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.

Magnetic Composite Scaffolds for Potential Applications in Radiochemotherapy of Malignant Bone Tumors.

Background and objectives: Cancer is the second leading cause of death globally, an alarming but expected increase. In comparison to other types of cancer, malignant bone tumors are unusual and their treatment is a real challenge. This paper's main purpose is the study of the potential application of composite scaffolds based on biopolymers and calcium phosphates with the inclusion of magnetic nanoparticles in combination therapy for malignant bone tumors. Materials and Methods: The first step was to investigate if X-rays could modify the scaffolds' properties. In vitro degradation of the scaffolds exposed to X-rays was analyzed, as well as their interaction with phosphate buffer solutions and cells. The second step was to load an anti-tumoral drug (doxorubicin) and to study in vitro drug release and its interaction with cells. The chemical structure of the scaffolds and their morphology were studied. Results: Analyses showed that X-ray irradiation did not influence the scaffolds' features. Doxorubicin release was gradual and its interaction with cells showed cytotoxic effects on cells after 72 h of direct contact. Conclusions: The obtained scaffolds could be considered in further studies regarding combination therapy for malignant bone tumors.

Sugar-based biopolymers as novel imaging agents for molecular magnetic resonance imaging.

Sugar-based biopolymers have been recognized as attractive materials to develop macromolecule- and nanoparticle-based cancer imaging and therapy. However, traditional biopolymer-based imaging approaches rely on the use of synthetic or isotopic labeling, and because of it, clinical translation often is hindered. Recently, a novel magnetic resonance imaging (MRI) technology, chemical exchange saturation transfer (CEST), has emerged, which allows the exploitation of sugar-based biopolymers as MRI agents by their hydroxyl protons-rich nature. In the study, we reviewed recent studies on the topic of CEST MRI detection of sugar-based biopolymers. The CEST MRI property of each biopolymer was briefly introduced, followed by the pre-clinical and clinical applications. The findings of these preliminary studies imply the enormous potential of CEST detectable sugar-based biopolymers in developing highly sensitive and translatable molecular imaging agents and constructing image-guided biopolymer-based drug delivery systems. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Curativo com filme e gel de biopolímero de celulose bacteriana no tratamento de feridas isquêmicas após revascularização de membros inferiores / Bacterial cellulose biopolymer film and gel dressing for the treatment of ischemic wounds after lower limb revascularization

RESUMO Objetivo: avaliar o uso do curativo de filme e gel de biopolímero de celulose bacteriana no tratamento de pacientes com feridas isquêmicas submetidos à revascularização dos membros inferiores. Métodos: ensaio clínico randomizado realizado no ambulatório de Angiologia e Cirurgia Vascular do Hospital das Clínicas da Universidade Federal de Pernambuco, entre janeiro de 2017 e dezembro de 2018. Foram acompanhados 24 pacientes após revascularização de membros inferiores, divididos em dois grupos: Experimental, tratado com filme e gel de biopolímero de celulose bacteriana, e Controle, tratado com ácidos graxos essenciais. Os pacientes foram acompanhados em consultas semanais para troca dos curativos e o processo de cicatrização das feridas foi avaliado em um período de 90 dias. Resultados: a redução da área das feridas isquêmicas no período de 30 dias foi de 4,3cm2 (55%), em média, para o grupo experimental, e de 5,5cm2 (48,5%) para o grupo controle (p>0,05). A taxa de cicatrização completa, em 90 dias, foi de 34,8%, sendo 50% no grupo experimental e 18,2% no grupo controle (p=0,053). Conclusão: o filme de biopolímero de celulose bacteriana associada a gel pode ser utilizado como curativo no tratamento de feridas isquêmicas de pacientes submetidos à revascularização de membros inferiores

ABSTRACT Objective: to evaluate the use of a bacterial cellulose biopolymer film and gel dressing in the treatment of patients with ischemic wounds submitted to lower limb revascularization. Methods: we conducted a randomized clinical trial in the Angiology and Vascular Surgery outpatient clinic of the Clinics Hospital of the Federal University of Pernambuco, between January 2017 and December 2018. We followed 24 patients after lower limb revascularization, divided into two groups: Experimental, treated with bacterial cellulose biopolymer film and gel, and Control, treated with essential fatty acids. Patients attended weekly appointments to change dressings and had their wound healing processes evaluated over a period of 90 days. Results: the reduction of the ischemic wounds' areas after 30 days was 4.3cm2 (55%) on average for the experimental group, and the 5.5cm2 (48.5%) for the control group (p>0.05). The complete healing rate at 90 days was 34.8%, 50% in the experimental group and 18.2% in the control group (p=0.053). Conclusion: the bacterial cellulose biopolymer film associated with gel can be used as a dressing in the treatment of ischemic wounds of patients undergoing revascularization of the lower limbs.

Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft. / Estudo experimental de reconstrução da veia femoral com enxerto tubular do bipolímero de cana-de-açúcar.

OBJECTIVE: to evaluate, through Doppler flowmetry, venography, histology and clinical evolution, the use of sugarcane biopolymer (BP) tubular grafts in the reconstruction of femoral veins in dogs. METHODS: we submitted eight adult dogs to femoral vein reconstruction, on the left with BP tubular graft and on the right with autologous vein. In the postoperative period, the animals underwent clinical evaluation and femoral vein Doppler flowmetry. After 360 days, we reoperated the dogs and submitted them to femoral vein phlebography with iodinated contrast. We removed the segments of the femoral veins containing the grafts and sent them for histopathological evaluation. RESULTS: the dogs did not present hemorrhage, hematoma, surgical wound infection or operated limb edema. One animal had superficial venous dilatation in the left inguinal region. Phlebography performed 360 days after the first surgery showed that three (37.5%) BP grafts and seven (87.5%) grafts from the control group (C) were patent. In the histopathological evaluation, we found an inflammatory reaction, with neutrophils and lymphocytes on the external surface of both groups. In the intimal layer of the grafts and in the outer layer in the two groups, we observed fibrosis. CONCLUSION: based on the results obtained with the experimental model used, BP presents potential to be used as a tubular graft for venous revascularization. However, new research must be performed to confirm its efficacy in the revascularization of medium and large diameter veins, which could allow its use in clinical practice.

OBJETIVO: avaliar, através de dopplerfluxometria, de venografia, de histologia e de evolução clínica, o uso de enxertos tubulares de biopolímero de cana-de-açúcar (BP) na reconstrução de veias femorais em cães. MÉTODOS: oito cães adultos foram submetidos à reconstrução de veia femoral, à esquerda com enxerto tubular de BP e à direita com veia autóloga. No período pós-operatório, os animais foram submetidos à avaliação clínica e dopplerfluxometria das veias femorais. Após 360 dias, os cães foram reoperados e submetidos à flebografia das veias femorais com contraste iodado. Os segmentos das veias femorais contendo os enxertos foram retirados e enviados para avaliação histopatológica. RESULTADOS: os cães não apresentaram hemorragia, hematoma, infecção da ferida operatória ou edema dos membros operados. Um animal apresentou dilatação venosa superficial na região inguinal esquerda. A flebografia realizada 360 dias após a primeira cirurgia demonstrou que três (37,5%) enxertos de BP e sete (87,5%) do grupo controle (C) estavam pérvios. Na avaliação histopatológica foi encontrada uma reação inflamatória com neutrófilos e linfócitos na superfície externa de ambos os grupos. Na camada íntima de revestimento dos enxertos e na camada externa nos dois grupos, foi encontrada fibrose. CONCLUSÃO: com base nos resultados obtidos com o modelo experimental utilizado, conclui-se que a BP apresenta potencial para ser utilizado como enxerto tubular para revascularização venosa, porém novas pesquisas precisam ser realizadas para confirmar a sua eficácia na revascularização de veias de médio e grande calibre, o que poderia permitir o seu uso na prática clínica.

New composite materials prepared by calcium phosphate precipitation in chitosan/collagen/hyaluronic acid sponge cross-linked by EDC/NHS.

Nowadays, fabrication of composite materials based on biopolymers is a rising field due to potential for bone repair and tissue engineering application. Blending of different biopolymers and incorporation of inorganic particles in the blend can lead to new materials with improved physicochemical properties and biocompatibility. In this work 3D porous structures called scaffolds based on chitosan, collagen and hyaluronic acid were obtained through the lyophilization process. Scaffolds were cross-linked by EDC/NHS. Infrared spectra for the materials were made, the percentage of swelling, scaffolds porosity and density, mechanical parameters, thermal stability were studied. Moreover, the scaffolds were used as matrixes for the calcium phosphate in situ precipitation. SEM images were taken and EDX analysis was carried out for calcium and phosphorous content determination in the scaffold. In addition, the adhesion and proliferation of human osteosarcoma SaOS-2 cells was examined on obtained scaffolds. The results showed that the properties of 3D composites cross-linked by EDC/NHS were altered after the addition of 1, 2 and 5% hyaluronic acid. Mechanical parameters, thermal stability and porosity of scaffolds were improved. Moreover, calcium and phosphorous were found in each kind of scaffold. SEM images showed that the precipitation was homogeneously carried in the whole volume of samples. Attachment of SaOS-2 cells to all modified materials was better compared to unmodified control and proliferation of these cells was markedly increased on scaffolds with precipitated calcium phosphate. Obtained materials can provide the support useful in tissue engineering and regenerative medicine.