Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction.

The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.

Stepwise dual-release microparticles of BMP-4 and SCF in induced pluripotent stem cell spheroids enhance differentiation into hematopoietic stem cells.

Recently, the formation of three-dimensional (3D) cell aggregates known as embryoid bodies (EBs) grown in media supplemented with HSC-specific morphogens has been utilized for the directed differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), into clinically relevant hematopoietic stem cells (HSCs). However, delivering growth factors and nutrients have become ineffective in inducing synchronous differentiation of cells due to their 3D conformation. Moreover, irregularly sized EBs often lead to the formation of necrotic cores in larger EBs, impairing differentiation. Here, we developed two gelatin microparticles (GelMPs) with different release patterns and two HSC-related growth factors conjugated to them. Slow and fast releasing GelMPs were conjugated with bone morphogenic factor-4 (BMP-4) and stem cell factor (SCF), respectively. The sequential presentation of BMP-4 and SCF in GelMPs resulted in efficient and effective hematopoietic differentiation, shown by the enhanced gene and protein expression of several mesoderm and HSC-related markers, and the increased concentration of released HSC-related cytokines. In the present study, we were able to generate CD34+, CD133+, and FLT3+ cells with similar cellular and molecular morphology as the naïve HSCs that can produce colony units of different blood cells, in vitro.

Effect of thermomechanical ageing on force transmission by orthodontic aligners made of different thermoformed materials: An experimental study.

OBJECTIVES: Investigating the impact of thermal and mechanical loading on the force generation of orthodontic aligners made from various thermoplastic materials and different compositions. MATERIALS AND METHODS: Five distinct materials were utilized including, three multi-layer (Zendura FLX, Zendura VIVA, CA Pro) and two single-layer (Zendura A and Duran). A total of 50 thermoformed aligners (n = 10) underwent a 48-hour ageing protocol, which involved mechanical loading resulting from a 0.2 mm facial malalignment of the upper right central incisor (Tooth 11) and thermal ageing through storage in warm distilled water at 37°C. The force exerted on Tooth 11 of a resin model was measured both before and after ageing using pressure-sensitive films and a biomechanical setup. RESULTS: Before ageing, pressure-sensitive films recorded normal contact forces ranging from 83.1 to 149.7 N, while the biomechanical setup measured resultant forces ranging from 0.1 to 0.5 N, with lingual forces exceeding facial forces. Multi-layer materials exhibited lower force magnitudes compared to single-layer materials. After ageing, a significant reduction in force was observed, with some materials experiencing up to a 50% decrease. Notably, multi-layer materials, especially Zendura VIVA, exhibited lower force decay. CONCLUSIONS: The force generated by aligners is influenced by both the aligner material and the direction of movement. Multi-layer materials exhibit superior performance compared to single-layer materials, primarily because of their lower initial force, which enhances patient comfort, and their capability to maintain consistent force application even after undergoing ageing.

Redefining vascular repair: revealing cellular responses on PEUU-gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models.

Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0 cm and a length of 11 cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.

Glycine/alginate-based piezoelectric film consisting of a single, monolithic ß-glycine spherulite towards flexible and biodegradable force sensor.

Development of piezoelectric biomaterials with high piezoelectric performance, while possessing excellent flexibility, biocompatibility, and biodegradability still remains a great challenge. Herein, a flexible, biocompatible and biodegradable piezoelectric ß-glycine-alginate-glycerol (Gly-Alg-Glycerol) film with excellent in vitro and in vivo sensing performance was developed. Remarkably, a single, monolithic ß-glycine spherulite, instead of more commonly observed multiple spherulites, was formed in alginate matrix, thereby resulting in outstanding piezoelectric property, including high piezoelectric constant (7.2 pC/N) and high piezoelectric sensitivity (1.97 mV/kPa). The Gly-Alg-Glycerol film exhibited superior flexibility, enabling complex shape-shifting, e.g. origami pigeon, 40% tensile strain, and repeated bending and folding deformation without fracture. In vitro, the flexible Gly-Alg-Glycerol film sensor could detect subtle pulse signal, sound wave and recognize shear stress applied from different directions. In addition, we have demonstrated that the Gly-Alg-Glycerol film sensor sealed by polylactic acid and beeswax could serve as an in vivo sensor to monitor physiological pressure signals such as heartbeat, respiration and muscle movement. Finally, the Gly-Alg-Glycerol film possessed good biocompatibility, supporting the attachment and proliferation of rat mesenchymal stromal cells, and biodegradability, thereby showing great potential as biodegradable piezoelectric biomaterials for biomedical sensing applications.

Biological properties versus solubility of endodontic sealers and cements.

Endodontic sealers and cements used in root canal treatment have different compositions and properties. Common to all materials is that their primary goal is to fill gaps and voids, making a permanent seal of the root canal system. Furthermore, aspects such as antibacterial properties, cytotoxicity, setting time, solubility and biocompatibility are also crucial and ought to be considered. Over the years, a shift in the view on the importance of these aspects has ocurred. Whereas the antibacterial properties were considered important when the technical factors in endodontics were less developed, the sealing ability and biocompatibility have later been considered the most critical factors. The introduction of tricalcium silicate cements and sealers has led to a renewed interest in material properties, as these cements seem to have good sealing ability and at the same time combine favourable antimicrobial effects with excellent biocompatibility. This review discusses how the various properties of root canal sealers and cements may conflict with the primary aim of providing a permanent seal of the root canal system.

Synthetic Cells and Molecules in Cellular Immunotherapy.

Cellular immunotherapy has emerged as an exciting strategy for cancer treatment, as it aims to enhance the body's immune response to tumor cells by engineering immune cells and designing synthetic molecules from scratch. Because of the cytotoxic nature, abundance in peripheral blood, and maturation of genetic engineering techniques, T cells have become the most commonly engineered immune cells to date. Represented by chimeric antigen receptor (CAR)-T therapy, T cell-based immunotherapy has revolutionized the clinical treatment of hematological malignancies. However, serious side effects and limited efficacy in solid tumors have hindered the clinical application of cellular immunotherapy. To address these limitations, various innovative strategies regarding synthetic cells and molecules have been developed. On one hand, some cytotoxic immune cells other than T cells have been engineered to explore the potential of targeted elimination of tumor cells, while some adjuvant cells have also been engineered to enhance the therapeutic effect. On the other hand, diverse synthetic cellular components and molecules are added to engineered immune cells to regulate their functions, promoting cytotoxic activity and restricting side effects. Moreover, novel bioactive materials such as hydrogels facilitating the delivery of therapeutic immune cells have also been applied to improve the efficacy of cellular immunotherapy. This review summarizes the innovative strategies of synthetic cells and molecules currently available in cellular immunotherapies, discusses the limitations, and provides insights into the next generation of cellular immunotherapies.

Skin repair and infection control in diabetic, obese mice using bioactive laser-activated sealants.

Conventional wound approximation devices, including sutures, staples, and glues, are widely used but risk of wound dehiscence, local infection, and scarring can be exacerbated in these approaches, including in diabetic and obese individuals. This study reports the efficacy and quality of tissue repair upon photothermal sealing of full-thickness incisional skin wounds using silk fibroin-based laser-activated sealants (LASEs) containing copper chloride salt (Cu-LASE) or silver nanoprisms (AgNPr-LASE), which absorb and convert near-infrared (NIR) laser energy to heat. LASE application results in rapid and effective skin sealing in healthy, immunodeficient, as well as diabetic and obese mice. Although lower recovery of epidermal structure and function was seen with AgNPr-LASE sealing, likely because of the hyperthermia induced by laser and presence of this material in the wound space, this approach resulted in higher enhancement in recovery of skin biomechanical strength compared to sutures and Cu-LASEs in diabetic, obese mice. Histological and immunohistochemical analyses revealed that AgNPr-LASEs resulted in significantly lower neutrophil migration to the wound compared to Cu-LASEs and sutures, indicating a more muted inflammatory response. Cu-LASEs resulted in local tissue toxicity likely because of effects of copper ions as manifested in the form of a significant epidermal gap and a 'depletion zone', which was a region devoid of viable cells proximal to the wound. Compared to sutures, LASE-mediated sealing, in later stages of healing, resulted in increased angiogenesis and diminished myofibroblast activation, which can be indicative of lower scarring. AgNPr-LASE loaded with vancomycin, an antibiotic drug, significantly lowered methicillin-resistant Staphylococcus aureus (MRSA) load in a pathogen challenge model in diabetic and obese mice and also reduced post-infection inflammation of tissue compared to antibacterial sutures. Taken together, these attributes indicate that AgNPr-LASE demonstrated a more balanced quality of tissue sealing and repair in diabetic and obese mice and can be used for combating local infections, that can result in poor healing in these individuals.

Conserved and tissue-specific immune responses to biologic scaffold implantation.

Upon implantation into a patient, any biomaterial induces a cascade of immune responses that influences the outcome of that device. This cascade depends upon several factors, including the composition of the material itself and the location in which the material is implanted. There is still significant uncertainty around the role of different tissue microenvironments in the immune response to biomaterials and how that may alter downstream scaffold remodeling and integration. In this study, we present a study evaluating the immune response to decellularized extracellular matrix materials within the intraperitoneal cavity, the subcutaneous space, and in a traumatic skeletal muscle injury microenvironment. All different locations induced robust cellular recruitment, specifically of macrophages and eosinophils. The latter was most prominent in the subcutaneous space. Intraperitoneal implants uniquely recruited B cells that may alter downstream reactivity as adaptive immunity has been strongly implicated in the outcome of scaffold remodeling. These data suggest that the location of tissue implants should be taken together with the composition of the material itself when designing devices for downline therapeutics. STATEMENT OF SIGNIFICANCE: Different tissue locations have unique immune microenvironments, which can influence the immune response to biomaterial implants. By considering the specific immune profiles of the target tissue, researchers can develop implant materials that promote better integration, reduce complications, and improve the overall outcome of the implantation process.

Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy.

Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.

Proof-of-principle of a lung sealant based on functionalized polyoxazolines: experiments in an ovine acute aerostasis model.

OBJECTIVES: More effective lung sealants are needed to prevent prolonged pulmonary air leakage (AL). Polyoxazoline-impregnated gelatin patch (N-hydroxysuccinimide ester functionalized poly(2-oxazoline)s; NHS-POx) was promising for lung sealing ex vivo. The aim of this study is to confirm sealing effectiveness in an in vivo model of lung injury. METHODS: An acute aerostasis model was used in healthy adult female sheep, involving bilateral thoracotomy, amputation lesions (bronchioles Ø > 1.5 mm), sealant application, digital chest tube for monitoring AL, spontaneous ventilation, obduction and bursting pressure measurement. Two experiments were performed: (i) 3 sheep with 2 lesions per lung (N = 4 NHS-POx double-layer, N = 4 NHS-POx single-layer, N = 4 untreated) and (ii) 3 with 1 lesion per lung (N = 3 NHS-POx single-layer, N = 3 untreated). In pooled linear regression, AL was analysed per lung (N = 7 NHS-POx, N = 5 untreated) and bursting pressure per lesion (N = 11 NHS-POx, N = 7 untreated). RESULTS: Baseline AL was similar between groups (mean 1.38-1.47 l/min, P = 0.90). NHS-POx achieved sealing in 1 attempt in 8/11 (72.7%) and in 10/11 (90.9%) in >1 attempt. Application failures were only observed on triangular lesions requiring 3 folds around the lung. No influences of methodological variation between experiments was detected in linear regression (P > 0.9). AL over initial 3 h of drainage was significantly reduced for NHS-POx [median: 7 ml/min, length of interquartile range: 333 ml/min] versus untreated lesions (367 ml/min, length of interquartile range: 680 ml/min, P = 0.036). Bursting pressure was higher for NHS-POx (mean: 33, SD: 16 cmH2O) versus untreated lesions (mean: 19, SD: 15 cmH2O, P = 0.081). CONCLUSIONS: NHS-POx was effective for reducing early AL, and a trend was seen for improvement of bursting strength of the covered defect. Results were affected by application characteristics and lesion geometry.

Recent advancements in natural polymers-based self-healing nano-materials for wound dressing.

The field of wound healing has witnessed remarkable progress in recent years, driven by the pursuit of advanced wound dressings. Traditional dressing materials have limitations like poor biocompatibility, nonbiodegradability, inadequate moisture management, poor breathability, lack of inherent therapeutic properties, and environmental impacts. There is a compelling demand for innovative solutions to transcend the constraints of conventional dressing materials for optimal wound care. In this extensive review, the therapeutic potential of natural polymers as the foundation for the development of self-healing nano-materials, specifically for wound dressing applications, has been elucidated. Natural polymers offer a multitude of advantages, possessing exceptional biocompatibility, biodegradability, and bioactivity. The intricate engineering strategies employed to fabricate these polymers into nanostructures, thereby imparting enhanced mechanical robustness, flexibility, critical for efficacious wound management has been expounded. By harnessing the inherent properties of natural polymers, including chitosan, alginate, collagen, hyaluronic acid, and so on, and integrating the concept of self-healing materials, a comprehensive overview of the cutting-edge research in this emerging field is presented in the review. Furthermore, the inherent self-healing attributes of these materials, wherein they exhibit innate capabilities to autonomously rectify any damage or disruption upon exposure to moisture or body fluids, reducing frequent dressing replacements have also been explored. This review consolidates the existing knowledge landscape, accentuating the benefits and challenges associated with these pioneering materials while concurrently paving the way for future investigations and translational applications in the realm of wound healing.

Molecular mechanisms of EGCG-CSH/n-HA/CMC in promoting osteogenic differentiation and macrophage polarization.

2. This research investigates the impact of the EGCG-CSH/n-HA/CMC composite material on bone defect repair, emphasizing its influence on macrophage polarization and osteogenic differentiation of BMSCs. Comprehensive evaluations of the composite's physical and chemical characteristics were performed. BMSC response to the material was tested in vitro for proliferation, migration, and osteogenic potential. An SD rat model was employed for in vivo assessments of bone repair efficacy. Both transcriptional and proteomic analyses were utilized to delineate the mechanisms influencing macrophage behavior and stem cell differentiation. The material maintained excellent structural integrity and significantly promoted BMSC functions critical to bone healing. In vivo results confirmed accelerated bone repair, and molecular analysis highlighted the role of macrophage M2 polarization, particularly through changes in the SIRPA gene and protein expression. EGCG-CSH/n-HA/CMC plays a significant role in enhancing bone repair, with implications for macrophage and BMSC function. Our findings suggest that targeting SIRPA may offer new therapeutic opportunities for bone regeneration.

Functional biomaterials for modulating the dysfunctional pathological microenvironment of spinal cord injury.

Spinal cord injury (SCI) often results in irreversible loss of sensory and motor functions, and most SCIs are incurable with current medical practice. One of the hardest challenges in treating SCI is the development of a dysfunctional pathological microenvironment, which mainly comprises excessive inflammation, deposition of inhibitory molecules, neurotrophic factor deprivation, glial scar formation, and imbalance of vascular function. To overcome this challenge, implantation of functional biomaterials at the injury site has been regarded as a potential treatment for modulating the dysfunctional microenvironment to support axon regeneration, remyelination at injury site, and functional recovery after SCI. This review summarizes characteristics of dysfunctional pathological microenvironment and recent advances in biomaterials as well as the technologies used to modulate inflammatory microenvironment, regulate inhibitory microenvironment, and reshape revascularization microenvironment. Moreover, technological limitations, challenges, and future prospects of functional biomaterials to promote efficient repair of SCI are also discussed. This review will aid further understanding and development of functional biomaterials to regulate pathological SCI microenvironment.

Intracellular magnetic hyperthermia reverses sorafenib resistance in hepatocellular carcinoma through its action on signaling pathways.

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.

Topical oxygen therapy as a novel strategy to promote wound healing and control the bacteria in implantology, oral surgery and periodontology: A review.

Globally, oral infections and inflammatory lesions persist as substantial public health concerns, necessitating the introduction of novel oral treatment protocols. Oral diseases are linked to various causative factors, with dental plaque/biofilm resulting from inadequate hygiene practices playing a predominant role. The strategic implementation of novel topical therapies holds promise for effectively controlling the biofilms, addressing oral infections and promoting enhanced oral wound healing. This review aims to providing a comprehensive overview of the available evidence pertaining to the potential efficacy of topical oxygen and lactoferrin-releasing biomaterials, exemplified by the blue®m formula, as novel oral care interventions within the scope of contemporary implantology, oral surgery and periodontology.

Platinum-Iridium Alloy Nanoparticle Coatings Produced by Electrophoretic Deposition Reduce Impedance in 3D Neural Electrodes.

Platinum-based neural electrodes frequently alloyed with Ir or W are routinely used for the treatment of neurological conditions. However, their performance is hampered by impaired electrical contact between electrode and tissue that compromises long-term implant stability. Though there are multiple coating techniques available to address this issue, electrode, and base material often exhibit a compositional mismatch, which impairs mechanical stability and may lead to toxicological side effects. In this work we coated Pt wire electrodes with ligand-free electrostatically stabilized colloidal Pt90Ir10, Pt90W10, and Pt50W50 alloy nanoparticles (NPs) matching electrode compositions using electrophoretic deposition (EPD) with direct-current (DC) and pulsed-DC fields in aqueous medium. The generated alloy NPs exhibit a solid solution structure as evidenced by HR-TEM-EDX and XRD, though additional WOx phases were identified in the Pt50W50 samples. Consequently, coating efficiency was also impaired in the presence of high W mass fractions in the alloy NPs. Characterization of the NP coatings by cyclic voltammetry and impedance spectroscopy yielded a significant reduction of the impedance in the Pt90Ir10 sample in comparison to the Pt control. The electrochemical surface area (ECSA) of the PtW alloy coatings, on the other hand, was significantly reduced.

Interaction-Based Perspective for Designing Polymer Biomaterial: A Strategic Approach to the Chitosan-Glycerophosphate System.

The conventional approach for developing any polymeric biomaterial is to follow protocols available in the literature and/or perform trial-and-error runs without a scientific basis. Here, we propose an analysis of a complex overlay of molecular interactions between drugs and polymers that provides a strategic pathway for biomaterial development. First, this work provides an innovative interaction-based method for developing an ocular formulation involving in situ gelling chitosan, gelatin, and glycerophosphate systems. A systematic interaction study is conducted based on the measurement of hydrodynamic radius, zeta potential, and viscosity with the sequential addition of formulation components. The increase in the hydrodynamic radius of the polymer with the addition of drugs can be interpreted as better diffusion of the drug inside the charged polymer chains and vice versa. Based on the knowledge of these interactions, a formulation has been designed that shows better drug release results with extended and sustained release compared to literature protocols, hence accentuating the importance of this study. An in-depth analysis of interactions can lead to a better understanding of the system. Second, we demonstrate the development of two dual-drug biomaterial systems, i.e., an in situ gelling and a liquid formulation at ocular surface temperature from the same polymers, which can be used as an ocular antiglaucoma formulation. Prior knowledge of the interactions between the drug polymers can be used to design a better formulation. The demonstrated application of this interaction-based protocol development can be extended universally to any biomaterial. This would provide a comprehensive idea about the properties and interactions of polymers and drugs, which can also serve as a base/starting point for a new formulation/biomaterial development.

Nanoformulations for the Diagnosis and Treatment of Metabolic Dysfunction-associated Steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive phase of metabolic dysfunction-associated steatotic liver disease (MASLD) that develops into irreversible liver cirrhosis and hepatocellular carcinoma, ultimately necessitating liver transplantation as the sole life-saving option. However, given the drawbacks of liver transplantation, including invasiveness, chronic immunosuppression, and a lack of donor livers, prompt diagnosis and effective treatment are indispensable. Due to the limitations of liver biopsy and conventional imaging modalities in diagnosing MASH, as well as the potential hazards associated with liver-protecting medicines, numerous nanoformulations have been created for MASH theranostics. Particularly, there has been significant study interest in artificial nanoparticles, natural biomaterials, and bionic nanoparticles that exhibit exceptional biocompatibility and bioavailability. In this review, we summarized extracellular vesicles (EVs)-based omics analysis and Fe3O4-based functional magnetic nanoparticles as magnetic resonance imaging (MRI) contrast agents for MASH diagnosis. Additionally, artificial nanoparticles such as organic and inorganic nanoparticles, as well as natural biomaterials such as cells and cell-derived EVs and bionic nanoparticles including cell membrane-coated nanoparticles, have also been reported for MASH treatment owing to their specific targeting and superior therapeutic effect. This review has the potential to stimulate advancements in nanoformulation fabrication techniques. By exploring their compatibility with cell biology, it could lead to the creation of innovative material systems for efficient theragnostic uses for MASH. STATEMENT OF SIGNIFICANCE: People with metabolic dysfunction-associated steatohepatitis (MASH) will progress to fibrosis, cirrhosis, or even liver cancer. It is imperative to establish effective theragnostic techniques to stop MASH from progressing into a lethal condition. In our review, we summarize the advancement of artificial, natural, and bionic nanoparticles applied in MASH theragnosis. Furthermore, the issues that need to be resolved for these cutting-edge techniques are summarized to realize a more significant clinical impact. We forecast the key fields that will advance further as nanotechnology and MASH research progress. Generally, our discovery has significant implications for the advancement of nanoformulation fabrication techniques, and their potential to be compatible with cell biology could lead to the creation of innovative materials systems for effective MASH theragnostic.