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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

The fabrication of biodegradable, bioabsorbable, and biocompatible vascular scaffolds with enhanced mechanical and biological properties that are able to modulate local inflammation and induce endothelialization after surgical implant is still a challenge. In this work, a fibrous scaffold, made of poly(ε‐caprolactone) and poly(glycerol sebacate), was fabricated to be potentially used as a small‐diameter graft in vascular surgery. The novelty of this research is represented by the direct incorporation of quercetin, a well‐known antioxidant compound with several biological properties, into a polymeric scaffold obtaining a vascular construct able to modulate two key factors involved in postsurgical inflammation, matrix metalloproteinase‐9 and endothelial nitric oxide synthase. For its production, an electrospinning apparatus, a solution made of the two polymers (both 20% (w/v), mixed at the ratio 1:1 (v/v)), and free quercetin (0.05% (w/v)) were used. Scanning electron and atomic force microscopies were employed to investigate the morphological properties of the fabricated electrospun scaffolds. Furthermore, physicochemical properties, including Fourier‐transform infrared spectroscopy, mass loss, fluid uptake, quercetin release, mechanical properties, and biological activity of the scaffolds were studied. The expression of matrix metalloproteinase‐9, tissue inhibitor of metalloproteinase‐1, and of endothelial nitric oxide synthase was evaluated when the quercetin‐functionalized scaffold was exposed to human endothelial cells treated with tumor necrosis factor‐α. The results of this study confirmed the feasibility of incorporating free quercetin during the electrospinning process to impart biological properties to small‐diameter vascular prostheses. [ABSTRACT FROM AUTHOR]

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.

Biomaterials are indispensable elements for improving human health and quality of life. Applications of biomaterials include the use of phantoms as tissue replacement in diagnostics (biosensors), medical supplies (blood bags and surgical instruments), therapeutic treatments (medical implants and devices), regenerative medicine (tissue engineered skin and cartilage), and radiation dosimetric studies. Since polymers are organic, they offer a much more versatile usage area than metals and ceramic biomaterials, particularly in soft tissue substitutes. The wide physical, mechanical, and chemical properties provided by polymers have encouraged extensive research, development, and application of polymeric biomaterials. Their usage as a soft tissue phantom is at the forefront of these applications. In this study, the ionization, recoils, phonon release, collision events, and lateral straggle properties of polymeric biomaterials [e.g., polymethylmetacrylate (PMMA), polystyrene, polyethylene, polypropylene, and polyvinylchloride] closest to soft tissue are investigated in carbon therapy application. The Brag peak location achieved for PMMA is quite close to that of soft tissue, within 4.8%, average recoils within 0.5%, and collision event parameter within 0.6%, however, lateral scattering is comparatively larger by roughly 6.8%, according to TRIM-based Monte Carlo simulation results. Thus, when carbon ion is taken into account, the current findings show that PMMA is one of the possible polymeric biomaterials to simulate soft tissue in terms of radiation interaction properties. [ABSTRACT FROM AUTHOR]

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.

[Display omitted] The aim of this study was the synthesis and evaluation of entirely S-protected thiolated hydroxyethylcellulose (HEC) with low and high viscosity, as well as thiolated poly-L-lysine (poly-L-Lys) used as dual-acting ionic as well as thiol-disulfide exchange mediated cross-linking hydrogel. Bis(mercaptosuccinic acid) was covalently attached to low and high viscous HECs via Fisher esterification, obtaining S-protected polymers. Poly-L-Lys-cysteine was synthesized via amidation of poly-L-Lys-HBr with cysteine (Cys). Thiolated polymers were examined in terms of cytotoxicity and rheological behavior of hydrogels containing these thiomers was evaluated with a cone-plate rheometer. Thiomers showed less cytotoxicity compared to the corresponding unmodified polymers. Rheological studies showed that cross-linking occurred between the two polymers via thiol-disulfide exchange reactions facilitated by the complementary charges. Employing poly-L-Lys-Cys in a concentration of either 0.5 or 5% (m/v) resulted in a 34.5-fold or 17.3-fold as well as a 53.6-fold or 29.6-fold improvement in dynamic viscosity within 5 min at 37 °C on S-protected thiolated low and high viscous HEC, compared to the corresponding unmodified HECs, respectively. By the combination of anionic S-protected thiolated polymers with a cationic thiolated polymer, dual-acting hydrogels exhibiting a time dependent increase in viscosity can be designed. [ABSTRACT FROM AUTHOR]

The application of bone grafting materials in bone tissue engineering is paramount for treating severe bone defects. In this comprehensive review, we explore the significance and novelty of utilizing bioactive polymers as grafts for successful bone repair. Unlike metals and ceramics, polymers offer inherent biodegradability and biocompatibility, mimicking the native extracellular matrix of bone. While these polymeric micro-nano materials may face challenges such as mechanical strength, various fabrication techniques are available to overcome these shortcomings. Our study not only investigates diverse biopolymeric materials but also illuminates innovative fabrication methods, highlighting their importance in advancing bone tissue engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

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.

Chronic wounds have been a global health threat over the past few decades, requiring urgent medical and research attention. The factors delaying the wound-healing process include obesity, stress, microbial infection, aging, edema, inadequate nutrition, poor oxygenation, diabetes, and implant complications. Biomaterials are being developed and fabricated to accelerate the healing of chronic wounds, including hydrogels, nanofibrous, composite, foam, spongy, bilayered, and trilayered scaffolds. Some recent advances in biomaterials development for healing both chronic and acute wounds are extensively compiled here. In addition, various properties of biomaterials for wound-healing applications and how they affect their performance are reviewed. Based on the recent literature, trilayered constructs appear to be a convincing candidate for the healing of chronic wounds and complete skin regeneration because they mimic the full thickness of skin: epidermis, dermis, and the hypodermis. This type of scaffold provides a dense superficial layer, a bioactive middle layer, and a porous lower layer to aid the wound-healing process. The hydrophilicity of scaffolds aids cell attachment, cell proliferation, and protein adhesion. Other scaffold characteristics such as porosity, biodegradability, mechanical properties, and gas permeability help with cell accommodation, proliferation, migration, differentiation, and the release of bioactive factors. [ABSTRACT FROM AUTHOR]

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.

Objectives : Evaluate in vitro the esthetic efficacy and cytotoxicity of a bleaching gel containing 35% hydrogen peroxide (BG-35%H2O2), applied for different time intervals, on enamel coated or not with polymeric biomaterials. Materials and methods: Nanofiber scaffolds (NSc) and a primer catalyst (PrCa) were used to coat the bovine enamel/dentin discs before the application of BG-35%H2O2, according to the following groups: G1—negative control (NC, without treatment); G2, G3, and G4—BG-35%H2O2 applied for 3 × 15, 2 × 15, and 15 min; G5, G6, and G7—BG-35%H2O2 applied on enamel coated with NSc and PrCa for 3 × 15; 2 × 15, and 15 min, respectively. The culture medium with components of gel diffused through the discs was applied on MDPC-23 cells, which were evaluated regarding to viability (VB), integrity of the membrane (IM), and oxidative stress (OxS). The quantity of H2O2 diffused and esthetic efficacy (ΔE/ΔWI) of the dental tissues were also analyzed (ANOVA/Tukey; p < 0.05). Results: Only G7 was similar to G1 regarding VB (p > 0.05). The lowest value of H2O2 diffusion occurred in G4 and G7, where the cells exhibited the lowest OxS than G2 (p < 0.05). Despite G5 showing the greatest ΔE regarding other groups (p < 0.05), the esthetic efficacy observed in G7 was similar to G2 (p > 0.05). ΔWI indicated a greater bleaching effect for groups G5, G6, and G7 (p < 0.05). Conclusion: Coating the dental enamel with polymeric biomaterials reduced the time and the cytotoxicity of BG-35%H2O2. Clinical significance. Coating the dental enamel with polymeric biomaterials allows safer and faster BG-35%H2O2 application. [ABSTRACT FROM AUTHOR]

Neuroprosthetics, with a range of applications such as cognitive, auditory, pain relief, recording, motor, and visual prosthetics have emerged as a promising field in recent years. However, poor electrical conductivity, a high disparity between tissue and interfaces and the onset of reactive gliosis post-implantation remains major challenges in the development of neuroprostheses. The choice of biomaterials in designing the neural interfaces' in neuroprosthetic applications is of high importance, as the overall sustained performance of neuroprosthetic devices is based on the features of materials used for the neural interfaces. Numerous biomaterials, such as metals and carbon-based materials, have been used in neuroprosthetics thus far. Nonetheless, neuroprosthetics made from polymeric biomaterials are in high demand due to their high biocompatibility, conductivity, and biostability. Furthermore, polymeric biomaterials can be used as a hybrid design to overcome the limitations of other co-biomaterials. This article makes an attempt to review the polymeric biomaterials involved in this cutting-edge technology utilized for different purposes such as substrates, coatings, and miniaturization of electrodes, that might help in enriching our understanding on neuroprosthetics. [ABSTRACT FROM AUTHOR]

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.

The scaffold is a porous three-dimensional (3D) material that supports cell growth and tissue regeneration. Such 3D structures should be generated with simple techniques and nontoxic ingredients to mimic bio-environment and facilitate tissue regeneration. In this work, simple but powerful techniques are demonstrated for the fabrication of lamellar and honeycomb-mimic scaffolds with poly(L-lactic acid). The honeycomb-mimic scaffolds with tunable pore size ranging from 70 to 160 µm are fabricated by crystal needle-guided thermally induced phase separation in a directional freezing apparatus. The compressive modulus of the honeycomb-mimic scaffold is ≈4 times higher than that of scaffold with randomly oriented pore structure. The fabricated honeycomb-mimic scaffold exhibits a hierarchical structure from nanofibers to micro-/macro-tubular structures. Pre-osteoblast MC3T3-E1 cells cultured on the honeycomb-mimic nanofibrous scaffolds exhibit an enhanced osteoblastic phenotype, with elevated expression levels of osteogenic marker genes, than those on either porous lamellar scaffolds or porous scaffolds with randomly oriented pores. The advanced techniques for the fabrication of the honeycomb-mimic structure may potentially be used for a wide variety of advanced functional materials., (© 2024 Wiley‐VCH GmbH.)

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.

This review focuses on the attachment of polymer brushes to polymeric biomaterial substrates by chemical surface modification methods for biomedical applications. In the first part of this paper, a general introduction to the synthesis of polymer brushes is given. Thereafter, a comprehensive overview of recent work on the chemical surface modification of polymeric biomaterials, with a focus on "grafting‐to," "grafting‐from," and "grafting‐through" strategies, is provided. Finally, some representative cutting‐edge biomedical applications of modified polymeric biomaterials, mainly including antifouling materials and biocompatible materials, are highlighted. On the basis of this literature study, a perspective on future trends in this field is provided. [ABSTRACT FROM AUTHOR]

A novel capability built upon secondary electron (SE) spectroscopy provides an enhanced cross‐linking characterization toolset for polymeric biomaterials, with cross‐linking density and variation captured at a multiscale level. The potential of SE spectroscopy for material characterization has been investigated since 1947. The absence of suitable instrumentation and signal processing proved insurmountable barriers to applying SE spectroscopy to biomaterials, and consequently, capturing SE spectra containing cross‐linking information is a new concept. To date, cross‐linking extent is inferred from analytical techniques such as nuclear magnetic resonance (NMR), differential scanning calorimetry, and Raman spectroscopy (RS). NMR provides extremely localized information on the atomic scale and molecular scale, while RS information volume is on the microscale. Other methods for the indirect study of cross‐linking are bulk mechanical averaging methods, such as tensile and compression modulus testing. However, these established averaging methods for the estimation of polymer cross‐linking density are incomplete because they fail to provide information of spatial distributions within the biomaterial morphology across all relevant length scales. The efficacy of the SE spectroscopy capability is demonstrated in this paper by the analysis of poly(glycerol sebacate)‐methacrylate (PGS‐M) at different degrees of methacrylation delivering new insights into PGS‐M morphology. [ABSTRACT FROM AUTHOR]

Objective: Development of stimuli-responsive intelligent drug delivery system (based on a polysaccharide, glucuronoxylan [GX]) with on-off switching properties under physiological conditions. Significance: As GX exhibits high swelling index and stimuli-responsive swelling/de-swelling properties, therefore, this material appeared highly useful to design pH, solvent and ionic stress-sensitive oral tablet formulations, which offered on-off switching properties. In this way, we could design intelligent/smart drug delivery systems for levosulpiride (LS) and theophylline (TF) with valuable pharmaceutical properties. Methods: GX-based tablet formulations were explored for stimuli-responsive, reversible swelling–deswelling behavior, dynamic swelling, and its kinetics. Tablet surface and channeling after swelling were observed using scanning electron microscopy (SEM). Drug release study was performed mimicking the physiological conditions like pH and transit time of gastrointestinal tract (GIT). Radiographic images of tablet path (in vivo) were recorded. Results: GX-based formulations exhibited high swelling in deionized water (DW), pH 6.8 and 7.4 while negligible swelling at pH 1.2. SEM images discovered the presence of microcracks and nanopores on the surface of tablets and showed channeling after swelling of tablets in DW. Sustained drug release was observed and found directly proportional to the concentration of GX in the formulations with negligible release at pH 1.2. In vivo radiographic evaluation indicated the retention of tablets in GIT for 7 h. Hemocompatibility studies showed the non-thrombogenic and non-hemolytic nature of GX. Conclusions: GX-based smart/stimuli-responsive formulations can control/sustain the release of drugs in GIT. [ABSTRACT FROM AUTHOR]

Intravascular oxygen delivery holds great potential to treat numerous hypoxic conditions and emergencies, including pulmonary disorders, hypoxic tumors, hemorrhagic shock, stroke, cardiac arrest and so on. Tremendous effort has been made in the past to find material solutions for the development of intravenous oxygen carriers and have ranged from blood substitutes to microbubbles with limited success. This paper highlights previous and recent progress in perfluorocarbon‐emulsions and microbubbles as intravenous gas carriers, including concerns over their long‐term stability, in vivo safety profiles, and oxygen transport efficacy. Their use as potential resuscitative therapeutics for treating various types of cardiac arrest is also discussed. Injectable oxygen: In this concept article, different biomaterials strategies to incorporate oxygen gas as injectable resuscitative therapeutics are discussed and compared, including perfluorocarbon emulsions and microbubbles stabilized by lipids and degradable polymers. [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.

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.)

The functional response of polymeric materials including biocompatibility and biodegradability in context of biomedical devices is governed by the macromolecular architecture, notably, random, block, star, graft and cross-linked polymers. The change in macromolecular architecture from diblock to triblock, linear to cyclic, star to dendritic, network to cross-linked (supra-molecular to covalent), etc. and their synthetic conditions govern the formation and properties of different materials for biological applications. For example, different self-assemblies and gelations from block copolymers, multi-molecular and uni-molecular self-assemblies from star polymers and dendrimers, unique thermal and hydrodynamic properties of cyclic polymer based systems compared to other polymeric materials, etc. A part of the review describes the different synthetic methods that are currently being employed to obtain biomaterials. While, the other part underscores the significance of macromolecular architectures on the properties of obtained materials. In summary, we elucidate here structure-molecular parameter-property relationships of macromolecular architecture in context of biomedical devices. [ABSTRACT FROM AUTHOR]