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The unique physical properties of heavy ion beams, particularly their distinctive depth–dose distribution and sharp lateral dose reduction profiles, have led to their widespread adoption in tumor therapy worldwide. However, the physical properties of heavy ion beams must be investigated to deliver a sufficient dose to tumors without damaging organs at risk. These studies should be performed on phantoms made of biomaterials that closely mimic human tissue. Polymers can serve as soft tissue substitutes and are suitable materials for building radiological phantoms due to their physical, mechanical, biological, and chemical properties. Extensive research, development, and applications of polymeric biomaterials have been encouraged due to these properties. In this study, we investigated the ionization, recoils, phonon release, collision events, and lateral straggle properties of polymeric biomaterials that closely resemble soft tissue using lithium-ion beams and Monte Carlo Transport of Ions in Matter simulation. The results indicated that the Bragg peak position closest to soft tissue was achieved with a 7.3% difference in polymethylmethacrylate, with an average recoils value of 10.5%. Additionally, average values of 33% were observed in collision events and 22.6% in lateral straggle. A significant contribution of this study to the existing literature lies in the exploration of secondary interactions alongside the assessment of linear energy transfer induced by the 7Li beam used for treatment. Furthermore, we analyzed the tissue-equivalent properties of polymer biomaterials using heavy ion beams, taking into account phonon release resulting from ionization, recoils, lateral straggle, and all other interactions. This approach allows for the evaluation of the most suitable polymeric biomaterials for heavy ion therapy while considering the full range of interactions involved. [ABSTRACT FROM AUTHOR]

Abstract Immune cell-based therapies are a rapidly emerging class of new medicines that directly treat and prevent targeted cancer. However multiple biological barriers impede the activity of live immune cells, and therefore necessitate the use of surface-modified immune cells for cancer prevention. Synthetic and/or natural biomaterials represent the leading approach for immune cell surface modulation. Different types of biomaterials can be applied to cell surface membranes through hydrophobic insertion, layer-by-layer attachment, and covalent conjugations to acquire surface modification in mammalian cells. These biomaterials generate reciprocity to enable cell–cell interactions. In this review, we highlight the different biomaterials (lipidic and polymeric)-based advanced applications for cell–surface modulation, a few cell recognition moieties, and how their interplay in cell–cell interaction. We discuss the cancer-killing efficacy of NK cells, followed by their surface engineering for cancer treatment. Ultimately, this review connects biomaterials and biologically active NK cells that play key roles in cancer immunotherapy applications. Graphical Abstract

Helium ion beam therapy, one of the particle therapies developed and studied in the 1950s for cancer treatment, resulted in clinical trials starting at Lawrence Berkeley National Laboratory in 1975. While proton and carbon ion therapies have been implemented in research institutions and hospitals globally after the end of the trials, progress in comprehending the physical, biological, and clinical findings of helium ion beam therapy has been limited, particularly due to its limited accessibility. Ongoing efforts aim to establish programs that evaluate the use of helium ion beams for clinical and research purposes, especially in the treatment of sensitive clinical cases. Additionally, helium ions have superior physical properties to proton beams, such as lower lateral scattering and larger LET. Moreover, they exhibit similar physical characteristics to carbon, oxygen, and neon ions, which are all used in heavy ion therapy. However, they demonstrate a sharper lateral penumbra with a lower radiobiological absence of certainties and lack the degradation of variations in dose distributions caused by excessive fragmenting of heavier-ion beams, especially at greater depths of penetration. In this context, the status and the prospective advancements of helium ion therapy are examined by investigating ionization, recoil, and lateral scattering values using MC TRIM algorithms in mandible plate phantoms designed from both tissue and previously studied biomaterials, providing an overview for dental cancer treatment. An average difference of 1.9% in the Bragg peak positions and 0.211 mm in lateral scattering was observed in both phantoms. Therefore, it is suggested that the 4He ion beam can be used in the treatment of mandibular tumors, and experimental research is recommended using the proposed biomaterial mandible plate phantom. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis is a chronic, inflammatory and potentially malignant oral disease. Local delivery of triamcinolone to lesion site is a commonly used therapy. The existing methods for local drug delivery include topical administration and submucosal injection. However, in the wet and dynamic oral microenvironment, these methods have drawbacks such as limited drug delivery efficiency and injection pain. Therefore, it is urgently needed to develop an alternative local drug delivery system with high efficiency and painlessness. Inspired by the structure of band-aid, this study proposed a novel double-layered mucoadhesive microneedle patch for transmucosal drug delivery. The patch consisted of a mucoadhesive silk fibroin/tannic acid top-layer and a silk fibroin microneedle under-layer. When applying the annealing condition for the medium content of β-sheets of silk fibroin, the microneedles in under-layer displayed both superior morphology and mechanical property. The mechanical strength of per needle (0.071N) was sufficient to penetrate the oral mucosa. Sequentially, the gelation efficiency of silk fibroin and tannic acid in top-layer was maximized as the weight ratio of tannic acid to silk fibroin reached 5:1. Moreover, in vitro results demonstrated the double-layered patch possessed undetectable cytotoxicity. The sustained release of triamcinolone was observed from the double-layered patch for at least 7 days. Furthermore, compared with other commercial buccal patches, the double-layered patch exhibited an enhanced wet adhesion strength of 37.74 kPa. In addition, ex vivo mucosal tissue penetration experiment confirmed that the double-layered patch could reach the lamina propria, ensuring effective drug delivery to the lesion site of oral submucous fibrosis. These results illustrate the promising potential of the drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis.

The eye has anatomical structures that function as robust static and dynamic barriers, limiting the penetration, residence time, and bioavailability of medications administered topically. The development of polymeric nano-based drug-delivery systems (DDS) could be the solution to these challenges: it can pass through ocular barriers, offering higher bioavailability of administered drugs to targeted tissues that are otherwise inaccessible; it can stay in ocular tissues for longer periods of time, requiring fewer drug administrations; and it can be made up of polymers that are biodegradable and nano-sized, minimizing the undesirable effects of the administered molecules. Therefore, therapeutic innovations in polymeric nano-based DDS have been widely explored for ophthalmic drug-delivery applications. In this review, we will give a comprehensive overview of polymeric nano-based drug-delivery systems (DDS) used in the treatment of ocular diseases. We will then examine the current therapeutic challenges of various ocular diseases and analyze how different types of biopolymers can potentially enhance our therapeutic options. A literature review of the preclinical and clinical studies published between 2017 and 2022 was conducted. Thanks to the advances in polymer science, the ocular DDS has rapidly evolved, showing great promise to help clinicians better manage patients. [ABSTRACT FROM AUTHOR]

Chronic wounds are one of the secondary health complications that develop in individuals who have poorly managed diabetes mellitus. This is often associated with delays in the wound healing process, resulting from long-term uncontrolled blood glucose levels. As such, an appropriate therapeutic approach would be maintaining blood glucose concentration within normal ranges, but this can be quite challenging to achieve. Consequently, diabetic ulcers usually require special medical care to prevent complications such as sepsis, amputation, and deformities, which often develop in these patients. Although several conventional wound dressings, such as hydrogels, gauze, films, and foams, are employed in the treatment of such chronic wounds, nanofibrous scaffolds have gained the attention of researchers because of their flexibility, ability to load a variety of bioactive compounds as single entities or combinations, and large surface area to volume ratio, which provides a biomimetic environment for cell proliferation relative to conventional dressings. Here, we present the current trends on the versatility of nanofibrous scaffolds as novel platforms for the incorporation of bioactive agents suitable for the enhancement of diabetic wound healing. [ABSTRACT FROM AUTHOR]

Skin indicates a person’s state of health and is so important that it influences a person’s emotional and psychological behavior. In this context, the effective treatment of wounds is a major concern, since several conventional wound healing materials have not been able to provide adequate healing, often leading to scar formation. Hence, the development of innovative biomaterials for wound healing is essential. Natural and synthetic polymers are used extensively for wound dressings and scaffold production. Both natural and synthetic polymers have beneficial properties and limitations, so they are often used in combination to overcome overcome their individual limitations. The use of different polymers in the production of biomaterials has proven to be a promising alternative for the treatment of wounds, as their capacity to accelerate the healing process has been demonstrated in many studies. Thus, this work focuses on describing several currently commercially available solutions used for the management of skin wounds, such as polymeric biomaterials for skin substitutes. New directions, strategies, and innovative technologies for the design of polymeric biomaterials are also addressed, providing solutions for deep burns, personalized care and faster healing.

The unique physical properties of heavy ion beams, particularly their distinctive depth–dose distribution and sharp lateral dose reduction profiles, have led to their widespread adoption in tumor therapy worldwide. However, the physical properties of heavy ion beams must be investigated to deliver a sufficient dose to tumors without damaging organs at risk. These studies should be performed on phantoms made of biomaterials that closely mimic human tissue. Polymers can serve as soft tissue substitutes and are suitable materials for building radiological phantoms due to their physical, mechanical, biological, and chemical properties. Extensive research, development, and applications of polymeric biomaterials have been encouraged due to these properties. In this study, we investigated the ionization, recoils, phonon release, collision events, and lateral straggle properties of polymeric biomaterials that closely resemble soft tissue using lithium-ion beams and Monte Carlo Transport of Ions in Matter simulation. The results indicated that the Bragg peak position closest to soft tissue was achieved with a 7.3% difference in polymethylmethacrylate, with an average recoils value of 10.5%. Additionally, average values of 33% were observed in collision events and 22.6% in lateral straggle. A significant contribution of this study to the existing literature lies in the exploration of secondary interactions alongside the assessment of linear energy transfer induced by the 7Li beam used for treatment. Furthermore, we analyzed the tissue-equivalent properties of polymer biomaterials using heavy ion beams, taking into account phonon release resulting from ionization, recoils, lateral straggle, and all other interactions. This approach allows for the evaluation of the most suitable polymeric biomaterials for heavy ion therapy while considering the full range of interactions involved.

Helium ion beam therapy, one of the particle therapies developed and studied in the 1950s for cancer treatment, resulted in clinical trials starting at Lawrence Berkeley National Laboratory in 1975. While proton and carbon ion therapies have been implemented in research institutions and hospitals globally after the end of the trials, progress in comprehending the physical, biological, and clinical findings of helium ion beam therapy has been limited, particularly due to its limited accessibility. Ongoing efforts aim to establish programs that evaluate the use of helium ion beams for clinical and research purposes, especially in the treatment of sensitive clinical cases. Additionally, helium ions have superior physical properties to proton beams, such as lower lateral scattering and larger LET. Moreover, they exhibit similar physical characteristics to carbon, oxygen, and neon ions, which are all used in heavy ion therapy. However, they demonstrate a sharper lateral penumbra with a lower radiobiological absence of certainties and lack the degradation of variations in dose distributions caused by excessive fragmenting of heavier-ion beams, especially at greater depths of penetration. In this context, the status and the prospective advancements of helium ion therapy are examined by investigating ionization, recoil, and lateral scattering values using MC TRIM algorithms in mandible plate phantoms designed from both tissue and previously studied biomaterials, providing an overview for dental cancer treatment. An average difference of 1.9% in the Bragg peak positions and 0.211 mm in lateral scattering was observed in both phantoms. Therefore, it is suggested that the 4He ion beam can be used in the treatment of mandibular tumors, and experimental research is recommended using the proposed biomaterial mandible plate phantom.

Abstract The current demand for patients’ organ and tissue repair and regeneration is continually increasing, where autologous or allograft is the golden standard treatment in the clinic. However, due to the shortage of donors, mismatched size and modality, functional loss of the donor region, possible immune rejection, and so forth, the application of auto‐/allo‐grafts is frequently hindered in many cases. In order to solve these problems, artificial constructs structurally and functionally imitating the extracellular matrix have been developed as substitutes to promoting cell attachment, proliferation, and differentiation, and ultimately forming functional tissues or organs for better tissue regeneration. Particularly, polymeric materials have been widely utilized in regenerative medicine because of their ease of manufacturing, flexibility, biocompatibility, as well as good mechanical, chemical, and thermal properties. This review presents a comprehensive overview of a variety of polymeric materials, their fabrication methods as well applications in regenerative medicine. Finally, we discussed the future challenges and perspectives in the development and clinical transformation of polymeric biomaterials.

Although there are several methods for fabricating nanofibrous scaffolds for biomedical applications, electrospinning is probably the most versatile and feasible process. Electrospinning enables the preparation of reproducible, homogeneous fibers from many types of polymers. In addition, implementation of this technique gives the possibility to fabricated polymer-based composite mats embroidered with manifold materials, such as graphene. Flake graphene and its derivatives represent an extremely promising material for imparting new, biomedically relevant properties, functions, and applications. Graphene oxide (GO) and reduced graphene oxide (rGO), among many extraordinary properties, confer antimicrobial properties of the resulting material. Moreover, graphene oxide and reduced graphene oxide promote the desired cellular response. Tissue engineering and regenerative medicine enable advanced treatments to regenerate damaged tissues and organs. This review provides a reliable summary of the recent scientific literature on the fabrication of nanofibers and their further modification with GO/rGO flakes for biomedical applications. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a high-prevalence joint disease characterized by the degradation of cartilage, subchondral bone thickening, and synovitis. Due to the inability of cartilage to self-repair, regenerative medicine strategies have become highly relevant in the management of osteoarthritis. Despite the great advances in medical and pharmaceutical sciences, current therapies stay unfulfilled, due to the inability of cartilage to repair itself. Additionally, the multifactorial etiology of the disease, including endogenous genetic dysfunctions and exogenous factors in many cases, also limits the formation of new cartilage extracellular matrix or impairs the regular recruiting of chondroprogenitor cells. Hence, current strategies for osteoarthritis management involve not only analgesics, anti-inflammatory drugs, and/or viscosupplementation but also polymeric biomaterials that are able to drive native cells to heal and repair the damaged cartilage. This review updates the most relevant research on osteoarthritis management that employs polymeric biomaterials capable of restoring the viscoelastic properties of cartilage, reducing the symptomatology, and favoring adequate cartilage regeneration properties. [ABSTRACT FROM AUTHOR]

Chronic wounds are one of the secondary health complications that develop in individuals who have poorly managed diabetes mellitus. This is often associated with delays in the wound healing process, resulting from long-term uncontrolled blood glucose levels. As such, an appropriate therapeutic approach would be maintaining blood glucose concentration within normal ranges, but this can be quite challenging to achieve. Consequently, diabetic ulcers usually require special medical care to prevent complications such as sepsis, amputation, and deformities, which often develop in these patients. Although several conventional wound dressings, such as hydrogels, gauze, films, and foams, are employed in the treatment of such chronic wounds, nanofibrous scaffolds have gained the attention of researchers because of their flexibility, ability to load a variety of bioactive compounds as single entities or combinations, and large surface area to volume ratio, which provides a biomimetic environment for cell proliferation relative to conventional dressings. Here, we present the current trends on the versatility of nanofibrous scaffolds as novel platforms for the incorporation of bioactive agents suitable for the enhancement of diabetic wound healing.

The eye has anatomical structures that function as robust static and dynamic barriers, limiting the penetration, residence time, and bioavailability of medications administered topically. The development of polymeric nano-based drug-delivery systems (DDS) could be the solution to these challenges: it can pass through ocular barriers, offering higher bioavailability of administered drugs to targeted tissues that are otherwise inaccessible; it can stay in ocular tissues for longer periods of time, requiring fewer drug administrations; and it can be made up of polymers that are biodegradable and nano-sized, minimizing the undesirable effects of the administered molecules. Therefore, therapeutic innovations in polymeric nano-based DDS have been widely explored for ophthalmic drug-delivery applications. In this review, we will give a comprehensive overview of polymeric nano-based drug-delivery systems (DDS) used in the treatment of ocular diseases. We will then examine the current therapeutic challenges of various ocular diseases and analyze how different types of biopolymers can potentially enhance our therapeutic options. A literature review of the preclinical and clinical studies published between 2017 and 2022 was conducted. Thanks to the advances in polymer science, the ocular DDS has rapidly evolved, showing great promise to help clinicians better manage patients.

Untreated articular cartilage damage normally results in osteoarthritis and even disability that affects millions of people. However, both the existing surgical treatment and tissue engineering approaches are unable to regenerate the original structures of articular cartilage durably, and new strategies for integrative cartilage repair are needed. Gene therapy provides local production of therapeutic factors, especially guided by biomaterials can minimize the diffusion and loss of the genes or gene complexes, achieve accurate spatiotemporally release of gene products, thus provideing long-term treatment for cartilage repair. The widespread application of gene therapy requires the development of safe and effective gene delivery vectors and supportive gene-activated matrices. Among them, polymeric biomaterials are particularly attractive due to their tunable physiochemical properties, as well as excellent adaptive performance. This paper reviews the recent advances in polymeric biomaterial-guided gene delivery for cartilage repair, with an emphasis on the important role of polymeric biomaterials in delivery systems.

Tissue architecture is a prerequisite for its biological functions. Recapitulating the three‐dimensional (3D) tissue structure represents one of the biggest challenges in tissue engineering. Two‐dimensional (2D) tissue fabrication methods are currently in the main stage for tissue engineering and disease modeling. However, due to their planar nature, the created models only represent very limited out‐of‐plane tissue structure. Here compressive buckling principle is harnessed to create 3D biomimetic cell‐laden microstructures from microfabricated planar patterns. This method allows out‐of‐plane delivery of cells and extracellular matrix patterns with high spatial precision. As a proof of principle, a variety of polymeric 3D miniature structures including a box, an octopus, a pyramid, and continuous waves are fabricated. A mineralized bone tissue model with spatially distributed cell‐laden lacunae structures is fabricated to demonstrate the fabrication power of the method. It is expected that this novel approach will help to significantly expand the utility of the established 2D fabrication techniques for 3D tissue fabrication. Given the widespread of 2D fabrication methods in biomedical research and the high demand for biomimetic 3D structures, this method is expected to bridge the gap between 2D and 3D tissue fabrication and open up new possibilities in tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract Tissue architecture is a prerequisite for its biological functions. Recapitulating the three‐dimensional (3D) tissue structure represents one of the biggest challenges in tissue engineering. Two‐dimensional (2D) tissue fabrication methods are currently in the main stage for tissue engineering and disease modeling. However, due to their planar nature, the created models only represent very limited out‐of‐plane tissue structure. Here compressive buckling principle is harnessed to create 3D biomimetic cell‐laden microstructures from microfabricated planar patterns. This method allows out‐of‐plane delivery of cells and extracellular matrix patterns with high spatial precision. As a proof of principle, a variety of polymeric 3D miniature structures including a box, an octopus, a pyramid, and continuous waves are fabricated. A mineralized bone tissue model with spatially distributed cell‐laden lacunae structures is fabricated to demonstrate the fabrication power of the method. It is expected that this novel approach will help to significantly expand the utility of the established 2D fabrication techniques for 3D tissue fabrication. Given the widespread of 2D fabrication methods in biomedical research and the high demand for biomimetic 3D structures, this method is expected to bridge the gap between 2D and 3D tissue fabrication and open up new possibilities in tissue engineering and regenerative medicine.

Although there are several methods for fabricating nanofibrous scaffolds for biomedical applications, electrospinning is probably the most versatile and feasible process. Electrospinning enables the preparation of reproducible, homogeneous fibers from many types of polymers. In addition, implementation of this technique gives the possibility to fabricated polymer-based composite mats embroidered with manifold materials, such as graphene. Flake graphene and its derivatives represent an extremely promising material for imparting new, biomedically relevant properties, functions, and applications. Graphene oxide (GO) and reduced graphene oxide (rGO), among many extraordinary properties, confer antimicrobial properties of the resulting material. Moreover, graphene oxide and reduced graphene oxide promote the desired cellular response. Tissue engineering and regenerative medicine enable advanced treatments to regenerate damaged tissues and organs. This review provides a reliable summary of the recent scientific literature on the fabrication of nanofibers and their further modification with GO/rGO flakes for biomedical applications.

Osteoarthritis is a high-prevalence joint disease characterized by the degradation of cartilage, subchondral bone thickening, and synovitis. Due to the inability of cartilage to self-repair, regenerative medicine strategies have become highly relevant in the management of osteoarthritis. Despite the great advances in medical and pharmaceutical sciences, current therapies stay unfulfilled, due to the inability of cartilage to repair itself. Additionally, the multifactorial etiology of the disease, including endogenous genetic dysfunctions and exogenous factors in many cases, also limits the formation of new cartilage extracellular matrix or impairs the regular recruiting of chondroprogenitor cells. Hence, current strategies for osteoarthritis management involve not only analgesics, anti-inflammatory drugs, and/or viscosupplementation but also polymeric biomaterials that are able to drive native cells to heal and repair the damaged cartilage. This review updates the most relevant research on osteoarthritis management that employs polymeric biomaterials capable of restoring the viscoelastic properties of cartilage, reducing the symptomatology, and favoring adequate cartilage regeneration properties.

Abstract Understanding the effects that sterilization methods have on the surface of a biomaterial is a prerequisite for clinical deployment. Sterilization causes alterations in a material's surface chemistry and surface structures that can result in significant changes to its cellular response. Here we compare surfaces resulting from the application of the industry standard autoclave sterilisation to that of surfaces resulting from the use of low‐pressure Argon glow discharge within a novel gas permeable packaging method in order to explore a potential new biomaterial sterilisation method. Material surfaces are assessed by applying secondary electron hyperspectral imaging (SEHI). SEHI is a novel low‐voltage scanning electron microscopy based characterization technique that, in addition to capturing topographical images, also provides nanoscale resolution chemical maps by utilizing the energy distribution of emitted secondary electrons. Here, SEHI maps are exploited to assess the lateral distributions of diverse functional groups that are effected by the sterilization treatments. This information combined with a range of conventional surface analysis techniques and a cellular metabolic activity assay reveals persuasive reasons as to why low‐pressure argon glow discharge should be considered for further optimization as a potential terminal sterilization method for PGS‐M, a functionalized form of poly(glycerol sebacate) (PGS).

Understanding the effects that sterilization methods have on the surface of a biomaterial is a prerequisite for clinical deployment. Sterilization causes alterations in a material's surface chemistry and surface structures that can result in significant changes to its cellular response. Here we compare surfaces resulting from the application of the industry standard autoclave sterilisation to that of surfaces resulting from the use of low‐pressure Argon glow discharge within a novel gas permeable packaging method in order to explore a potential new biomaterial sterilisation method. Material surfaces are assessed by applying secondary electron hyperspectral imaging (SEHI). SEHI is a novel low‐voltage scanning electron microscopy based characterization technique that, in addition to capturing topographical images, also provides nanoscale resolution chemical maps by utilizing the energy distribution of emitted secondary electrons. Here, SEHI maps are exploited to assess the lateral distributions of diverse functional groups that are effected by the sterilization treatments. This information combined with a range of conventional surface analysis techniques and a cellular metabolic activity assay reveals persuasive reasons as to why low‐pressure argon glow discharge should be considered for further optimization as a potential terminal sterilization method for PGS‐M, a functionalized form of poly(glycerol sebacate) (PGS). [ABSTRACT FROM AUTHOR]

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received "conventional" SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future. [ABSTRACT FROM AUTHOR]

The hypothesis of the present research is that by altering the substrate topography and/or stiffness to make it biomimetic, we can modulate cells behavior. Substrates with similar surface chemistry and varying stiffnesses and topographies were prepared. Bulk PCL and CNTs-reinforced PCL composites were manufactured by solvent casting method and electrospinning and further processed to obtain tunable moduli of elasticity in the range of few MPa. To ensure the same chemical profile for the substrates, a protein coating was added. Substrate topography and properties were investigated. Further on, the feedback of Wharton’s Jelly Umbilical Cord Mesenchymal Stem Cells to substrates characteristics was investigated. Solvent casting scaffolds displayed superior mechanical properties compared to the corresponding electrospun films. However, the biomimetic fibrous texture of the electrospun substrates induced improved feedback of the cells with respect to their viability and proliferation. Cells’ adhesion and differentiation was remarkably pronounced on solvent casting substrates compared to the electrospun substrates. Soft substates improved cells multiplication and migration, while stiff substrates induced differentiation into bone cells. Aspects related to the key factors and the ideal properties of substrates and microenvironments were clarified, aiming towards the deep understanding of the required optimum biomimetic features of biomaterials.

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received “conventional” SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future.

Ganciclovir and valganciclor are antiviral agents used for the treatment of cytomegalovirus retinitis. The conventional method for administering ganciclovir in cytomegalovirus retinitis patients is repeated intravitreal injections. In order to obviate the possible detrimental effects of repeated intraocular injections, to improve compliance and to eliminate systemic side-effects, we investigated the tuning of the ganciclovir pro-drug valganciclovir and the release from thin films of poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), or mixtures of both, as a step towards prototyping periocular valganciclovir implants. To investigate the drug release, we established and evaluated a high throughput fluorescence-based quantification screening assay for the detection of valganciclovir. Our protocol allows quantifying as little as 20 ng of valganciclovir in 96-well polypropylene plates and a 50× faster analysis compared to traditional HPLC measurements. This improvement can hence be extrapolated to other polyester matrix thin film formulations using a high-throughput approach. The acidic microenvironment within the polyester matrix was found to protect valganciclovir from degradation with resultant increases in the half-life of the drug in the periocular implant to 100 days. Linear release profiles were obtained using the pure polyester polymers for 10 days and 60 days formulations; however, gross phase separations of PCL and acid-terminated PLGA prevented tuning within these timeframes due to the phase separation of the polymer, valganciclovir, or both.

Oral submucous fibrosis is a chronic, inflammatory and potentially malignant oral disease. Local delivery of triamcinolone to lesion site is a commonly used therapy. The existing methods for local drug delivery include topical administration and submucosal injection. However, in the wet and dynamic oral microenvironment, these methods have drawbacks such as limited drug delivery efficiency and injection pain. Therefore, it is urgently needed to develop an alternative local drug delivery system with high efficiency and painlessness. Inspired by the structure of band-aid, this study proposed a novel double-layered mucoadhesive microneedle patch for transmucosal drug delivery. The patch consisted of a mucoadhesive silk fibroin/tannic acid top-layer and a silk fibroin microneedle under-layer. When applying the annealing condition for the medium content of β-sheets of silk fibroin, the microneedles in under-layer displayed both superior morphology and mechanical property. The mechanical strength of per needle (0.071N) was sufficient to penetrate the oral mucosa. Sequentially, the gelation efficiency of silk fibroin and tannic acid in top-layer was maximized as the weight ratio of tannic acid to silk fibroin reached 5:1. Moreover, in vitro results demonstrated the double-layered patch possessed undetectable cytotoxicity. The sustained release of triamcinolone was observed from the double-layered patch for at least 7 days. Furthermore, compared with other commercial buccal patches, the double-layered patch exhibited an enhanced wet adhesion strength of 37.74 kPa. In addition, ex vivo mucosal tissue penetration experiment confirmed that the double-layered patch could reach the lamina propria, ensuring effective drug delivery to the lesion site of oral submucous fibrosis. These results illustrate the promising potential of the drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cheng, Yang, Liao, Yi, Zhou, Dai, Liu and Liu.)

Wounds are of a variety of types and each category has its own distinctive healing requirements. This realization has spurred the development of a myriad of wound dressings, each with specific characteristics. It is unrealistic to expect a singular dressing to embrace all characteristics that would fulfill generic needs for wound healing. However, each dressing may approach the ideal requirements by deviating from the ‘one size fits all approach’, if it conforms strictly to the specifications of the wound and the patient. Indeed, a functional wound dressing should achieve healing of the wound with minimal time and cost expenditures. This article offers an insight into several different types of polymeric materials clinically used in wound dressings and the events taking place at cellular level, which aid the process of healing, while the biomaterial dressing interacts with the body tissue. Hence, the significance of using synthetic polymer films, foam dressings, hydrocolloids, alginate dressings, and hydrogels has been reviewed, and the properties of these materials that conform to wound-healing requirements have been explored. A special section on bioactive dressings and bioengineered skin substitutes that play an active part in healing process has been re-examined in this work. [ABSTRACT FROM AUTHOR]

Biomaterials are mostly polymers and are used in artificial organ production in contemporary medicine. They are prepared by the polymerization reaction of many monomers. There are many monomers used in biomaterial production. In this study, we investigated whether acrylamide (AAm), methacrylamide (MAAm), N-isopropylacrylamide (NIPAm) and acrylic acid (AAc) used in polymeric biomaterial production had histopathological effects on renal tissue. In the present study, Wistar albino rats weighing ~ 250-300 g were used. Following the intramuscular injections of 1 mL aqueous monomer solutions at 50 mg/kg concentrations, acrylamide group animals were sacrificed at 1st, 2nd and 3rd weeks, the other monomer group animals were sacrificed at 1st, 2nd, 4th and 6th weeks. One mL serum physiologic were injected intramuscularly to the control group animals at the same time intervals with the experimental group animals. After histological follow-up, serial sections were prepared for evaluation under light microscope. In addition, the diameters of glomeruli and glomeruli space (Bowman's space) are measured, and the changes of the values of all groups with the exposure time were investigated. Acrylamide and its derivatives cause glomerular, arteriolar and tubule interstitial damage in the renal tissue. The narrowing glomeruli space, increasing diffuse mesangial matrix and tubular dilation was observed in some groups. In addition, dilatation, dissociation of tubular epithelium, thickening basement membranes and glycogenic vacuolization was also noted. These adverse results may be due to residual monomer. There should be no monomer residue in the polymer used as biomaterials. [ABSTRACT FROM AUTHOR]

In this study, new composite bisphosphonate delivery systems were obtained from polyurethanes (PUs) and nanocrystalline hydroxyapatite (HA). The biodegradable PUs were first synthesized from poly(ε-caprolactone) diols (PCL diols), poly(ethylene adipate) diol, 1,6-hexamethylene diisocyanate, 1,4-butanediol and HA. Moreover, the PCL diols were synthesized by the ring-opening polymerization catalysed by the lipase from Candida antarctica. Next, composite drug delivery systems for clodronate were prepared. The mechanical properties of the obtained biomaterials were determined. The cytotoxicity of the synthesized polymers was tested. The preliminary results show that the obtained composites are perspective biomaterials and they can be potentially applied in the technology of implantation drug delivery systems.

Aerogels were obtained from laccase/TEMPO-oxidized galactomannans (GM) of the leguminous plants: fenugreek, sesbania and guar, with several potential applications, such as biocompatible, biodegradable “delivery systems” (DS) of active principles. Chemo-enzymatic oxidation of GM in aqueous solution caused a viscosity increase up to fifteen-fold, generating structured, elastic, and stable hydrogels, presumably due to formation of carbonyl groups from primary OH’s on the polymers and subsequent establishment of hemiacetalic bonds with available free hydroxyl groups. Upon lyophilization of these hydrogels, water-insoluble aerogels were generated, capable of uptaking an aqueous solution several times their own weight. In the present paper, these aerogels were further characterized by ESI-MS after enzymatic depolymerization, scanning electron microscopy, thermal and X-ray analyses. Fenugreek confirmed to be more structured and stable compared to guar and sesbania aerogels, which is likely due to its higher amount of oxidizable galactose units linked to the mannose backbone (i.e., Gal : Man = 1:1) and, therefore, to more extensive cross-linking of the resulting elastic gel. [ABSTRACT FROM AUTHOR]

A new theranostic ultrasmall superparamagnetic iron oxide nanoparticle (USPIONP)—consisting of an iron oxide nanoparticle (IONP) core, amphiphilic poly(aspartic acid) graft copolymer (P), and a model anticancer drug, epirubicin (EPI)—was developed and characterized. The graft copolymer P, poly(2-hydroxyethylaspartamide)-mPEG-C 16 , was synthesized by a polysuccinimide ring-opening reaction. The P-IONP, the IONP core of which was coated with polymer P, was synthesized using a co-precipitation method. The P-IONP was a USPIONP with an IONP core of diameter 6–9 nm and a hydrodynamic diameter of 41 nm. The EPI-loaded P-IONP (EPI-P-IONP) had a hydrodynamic diameter of 53 nm. The remarkably high relaxivity, r 2 , of 605.5 s −1 mM −1 of EPI-P-IONP corresponded to magnetic resonance contrast enhancement 2.7-fold that of a commercial contrast agent. The EPI encapsulation efficiency was 81%, and EPI was released from EPI-P-IONP in a sustained manner. P-IONP had negligible cytotoxicity against HeLa cells, while cytotoxicity increased in an EPI-dose-dependent manner after 4 h incubation with EPI-P-IONP. Cellular uptake of EPI from EPI-P-IONP was comparable to that of free EPI, as determined by flow cytometry. Confocal microscopy confirmed nuclear uptake of EPI released from EPI-P-IONP. These results suggest that the P-IONP has potential as an imaging agent and a therapeutic agent, and thus as a theranostic agent. [ABSTRACT FROM AUTHOR]

Engineered scaffolds produced by electrospinning of biodegradable polymers offer a 3D, nanofibrous environment with controllable structural, chemical, and mechanical properties that mimic the extracellular matrix of native tissues and have shown promise for a number of tissue engineering applications. The microscale mechanical interactions between cells and electrospun matrices drive cell behaviors including migration and differentiation that are critical to promote tissue regeneration. Recent developments in understanding these mechanical interactions in electrospun environments are reviewed, with emphasis on how fiber geometry and polymer structure impact on the local mechanical properties of scaffolds, how altering the micromechanics cues cell behaviors, and how, in turn, cellular and extrinsic forces exerted on the matrix mechanically remodel an electrospun scaffold throughout tissue development. Techniques used to measure and visualize these mechanical interactions are described. We provide a critical outlook on technological gaps that must be overcome to advance the ability to design, assess, and manipulate the mechanical environment in electrospun scaffolds toward constructs that may be successfully applied in tissue engineering and regenerative medicine. Statement of Significance Tissue engineering requires design of scaffolds that interact with cells to promote tissue development. Electrospinning is a promising technique for fabricating fibrous, biomimetic scaffolds. Effects of electrospun matrix microstructure and biochemical properties on cell behavior have been extensively reviewed previously; here, we consider cell-matrix interaction from a mechanical perspective. Micromechanical properties as a driver of cell behavior has been well established in planar substrates, but more recently, many studies have provided new insights into mechanical interaction in fibrillar, electrospun environments. This review provides readers with an overview of how electrospun scaffold mechanics and cell behavior work in a dynamic feedback loop to drive tissue development, and discusses opportunities for improved design of mechanical environments that are conducive to tissue development. [ABSTRACT FROM AUTHOR]

The use of amine-terminated poly(ethylene glycol) star polymers as macroinitiators for the N-carboxyanhydride ring-opening polymerisation of S- tert -butylmercapto- l -cysteine N-carboxahydride is described to yield amphiphilic copolymers that are capable of forming discrete particles in aqueous solution. Poly(amino acid) deprotection liberates the pendant thiol groups that can then form covalent disulfide crosslinks with adjacent thiol groups and yield a crosslinked polymer that is capable of hydrogel formation. The model protein albumin–fluorescein isothiocyanate conjugate was encapsulated within the hydrogels produced, prior to its release upon hydrogel interaction with the reducing agent glutathione. Consequently, the stimuli-responsive polymers formed hold great promise as biomaterials capable of releasing a protein molecular cargo upon interaction with glutathione. [ABSTRACT FROM AUTHOR]

Skin indicates a person's state of health and is so important that it influences a person's emotional and psychological behavior. In this context, the effective treatment of wounds is a major concern, since several conventional wound healing materials have not been able to provide adequate healing, often leading to scar formation. Hence, the development of innovative biomaterials for wound healing is essential. Natural and synthetic polymers are used extensively for wound dressings and scaffold production. Both natural and synthetic polymers have beneficial properties and limitations, so they are often used in combination to overcome overcome their individual limitations. The use of different polymers in the production of biomaterials has proven to be a promising alternative for the treatment of wounds, as their capacity to accelerate the healing process has been demonstrated in many studies. Thus, this work focuses on describing several currently commercially available solutions used for the management of skin wounds, such as polymeric biomaterials for skin substitutes. New directions, strategies, and innovative technologies for the design of polymeric biomaterials are also addressed, providing solutions for deep burns, personalized care and faster healing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Oliveira, Sousa, Teixeira, Ferreira-Santos and Botelho.)

When biodegradable polyester devices, like sutures and screws, are implanted into the body, it is very challenging to image them in deep tissue, monitor their degradation, and detect defects. We report our recent findings on non-invasive deep tissue imaging of polyester degradation, stability and integrity using an iodinated-polycaprolactone (i-P(CLcoOPD)) X-ray imaging contrast agent. The results of experiments performed with i-P(CLcoOPD) demonstrate the feasibility to quantify in-situ polyester degradation in vitro and in vivo using rats. We also demonstrate that X-ray imaging could be used to identify and quantify physical defects, such as cracks, in polymeric implants using rabbit animal models. This approach enables non-invasive monitoring of polyester materials and is expected to become an important technology for improving the imaging of polymers at clinically relevant depths. [ABSTRACT FROM AUTHOR]

Ganciclovir and valganciclor are antiviral agents used for the treatment of cytomegalovirus retinitis. The conventional method for administering ganciclovir in cytomegalovirus retinitis patients is repeated intravitreal injections. In order to obviate the possible detrimental effects of repeated intraocular injections, to improve compliance and to eliminate systemic side-effects, we investigated the tuning of the ganciclovir pro-drug valganciclovir and the release from thin films of poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), or mixtures of both, as a step towards prototyping periocular valganciclovir implants. To investigate the drug release, we established and evaluated a high throughput fluorescence-based quantification screening assay for the detection of valganciclovir. Our protocol allows quantifying as little as 20 ng of valganciclovir in 96-well polypropylene plates and a 50× faster analysis compared to traditional HPLC measurements. This improvement can hence be extrapolated to other polyester matrix thin film formulations using a high-throughput approach. The acidic microenvironment within the polyester matrix was found to protect valganciclovir from degradation with resultant increases in the half-life of the drug in the periocular implant to 100 days. Linear release profiles were obtained using the pure polyester polymers for 10 days and 60 days formulations; however, gross phase separations of PCL and acid-terminated PLGA prevented tuning within these timeframes due to the phase separation of the polymer, valganciclovir, or both. [ABSTRACT FROM AUTHOR]

The wetting behavior of polymeric biomaterials is of great importance for biomedical research and pharmaceutical applications. Tailoring of polymer surface wettability is particularly effective to address biomedical issues such as biofouling control and biocompatibility improvement. In this paper, we conducted comprehensive experiments and analytical modeling to understand the effects of a consecutive-O2-SF6 plasma treatment on the super hydrophobicity of parylene-C. Experimentally, super hydrophobic parylene-C surfaces with a maximum water contact angle of ~169° have been successfully achieved. Atomic force microscopy and X-ray photoelectron spectroscopy results strongly suggest that the modification of surface wettability can be attributed to the variation in surface roughness and the plasma-induced surface chemistry. Analytically, a transition of droplet status from the Wenzel state to the Cassie state on hydrophobic parylene-C surfaces has been demonstrated after sufficient roughening by O2 plasma pre-treatment. The surface morphology of plasma-treated parylene-C films has also been analyzed and the hexagonal-close-packed model of downward crowns shows the best agreement with experimental results. Our simple and time-efficient treatment eliminates the need for creating well-defined patterns, is completely compatible with conventional microfabrication techniques, and can also be applied to curved parylene surfaces. [ABSTRACT FROM AUTHOR]

Pectin is a heteropolysaccharide which has been investigated for the development of colon-specific drug delivery systems. Polymers have been associated with pectin to reduce its aqueous solubility and improve the performance of drug delivery systems. Pectin-casein interaction is widely known in food research, but it has not been fully considered by pharmaceutical scientists. Thus, this study investigated the potential of casein-pectin microparticles as a drug delivery system and clarified the impact of cross-linking and drying methods on the in vitro release of indomethacin (IND) or acetaminophen (PCT) from microparticles. Microparticles were prepared by coacervation and dried by spray or spouted bed methods. Drug recovery, in vitro drug release, size, morphology, and the thermal and diffractometric properties of dried microparticles were determined. Spray-dried non-cross-linked microparticles were able to prolong IND release, and pectin was still degraded by pectinolytic enzymes. On the other hand, glutaraldehyde cross-linking prevented the enzymatic breakdown of pectin without improving IND release. Spouted bed drying reduced IND recovery from all microparticles when compared with spray drying, thus the successful spouted bed drying of microparticles depends on the chemical characteristics of both the drug and the polymer. Release data from PCT microparticles suggested that the microparticle formulation should be improved to bring about a more efficient delivery of water-soluble drugs. In conclusion, casein-pectin microparticles show great potential as a drug delivery system because casein reduces the water solubility of pectin. The drying method and cross-linking process had significant effects on the in vitro performance of these microparticles. [ABSTRACT FROM AUTHOR]

Abstract: Immunofluorescence imaging on polymeric biomaterials is often inhibited by autofluorescence and other optical phenomena. This often limits the analysis that can be performed on cells that are in contact with these materials. This study outlines a method that will quench these inhibitive optical phenomena on a variety of polymeric materials, including poly(glycerol sebacate), poly(urethane), poly(l-lactide–co-ε-caprolactone), and poly(lactic acid–co-glycolic acid). The method uses a simple material treatment method utilizing Sudan Black B (SB), which is commonly used as an autofluorescence quenching molecule in tissue histology, but has not yet been used in biomaterials analysis. The quenching mechanism in the selected polymers is investigated using attenuated total reflectance Fourier transform infrared spectroscoy, ultraviolet–visible light absorbance and fluorescence analysis, and scanning electron microscopyobservation of the material morphology prior to and after SB treatment. The results point to SB eliminating the inhibitive light phenomena of these materials by two methods: (i) chemical interaction between SB and the polymer molecules and (ii) physical interaction whereby SB forms a physical barrier that can absorb scattered light and quench autofluorescence interference during fluorescence microscopy. The studies show that the treatment of polymers with SB is robust across the polymers tested, in both porous and non-porous formats. The method does not interfere with immunofluorescent imaging of fluorescently labeled biological cells cultured on these polymers. This quick, simple, and affordable method enables a variety of analyses to be conducted that may otherwise have been impractical or impossible. [Copyright &y& Elsevier]

Abstract: Porosity and pore size of biomaterial scaffolds play a critical role in bone formation in vitro and in vivo. This review explores the state of knowledge regarding the relationship between porosity and pore size of biomaterials used for bone regeneration. The effect of these morphological features on osteogenesis in vitro and in vivo, as well as relationships to mechanical properties of the scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by suppressing cell proliferation and forcing cell aggregation. In contrast, in vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion that is supported by the absence of reports that show enhanced osteogenic outcomes for scaffolds with low void volumes. However, this trend results in diminished mechanical properties, thereby setting an upper functional limit for pore size and porosity. Thus, a balance must be reached depending on the repair, rate of remodeling and rate of degradation of the scaffold material. Based on early studies, the minimum requirement for pore size is considered to be ∼100μm due to cell size, migration requirements and transport. However, pore sizes >300μm are recommended, due to enhanced new bone formation and the formation of capillaries. Because of vasculariziation, pore size has been shown to affect the progression of osteogenesis. Small pores favored hypoxic conditions and induced osteochondral formation before osteogenesis, while large pores, that are well-vascularized, lead to direct osteogenesis (without preceding cartilage formation). Gradients in pore sizes are recommended for future studies focused on the formation of multiple tissues and tissue interfaces. New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bone-repair needs. [Copyright &y& Elsevier]