Showing papers by "Subhas C. Kundu published in 2023"
TL;DR: In this paper , a PAA-based coacervate hydrogel with strong wet adhesion capability is fabricated through a facile mixture of PAA copolymers with isoprenyl oxy poly(ethylene glycol) ether and tannic acid (TA).
Abstract: Polyacrylic acid (PAA) and its derivatives are commonly used as essential matrices in wound dressings, but their weak wet adhesion restricts the clinical application. To address this issue, a PAA‐based coacervate hydrogel with strong wet adhesion capability is fabricated through a facile mixture of PAA copolymers with isoprenyl oxy poly(ethylene glycol) ether and tannic acid (TA). The poly(ethylene glycol) segments on PAA prevent the electrostatic repulsion among the ionized carboxyl groups and absorbed TA to form coacervates. The absorbed TA provides solid adhesion to dry and wet substrates via multifarious interactions, which endows the coacervate with an adhesive strength to skin of 23.4 kPa and 70% adhesion underwater. This coacervate achieves desirable self‐healing and extensible properties suitable for frequently moving joints. These investigations prove that the coacervate has strong antibacterial activity, facilitates fibroblast migration, and modulates M1/M2 polarization of macrophages. In vivo hemorrhage experiments further confirm that the coacervate dramatically shortens the hemostatic time from hundreds to tens of seconds. In addition, full‐thickness skin defect experiments demonstrate that the coacervate achieves the best therapeutic effect by significantly promoting collagen deposition, angiogenesis, and epithelialization. These results demonstrate that a PAA‐based coacervate hydrogel is a promising wound dressing for medical translation.
2 citations
TL;DR: In this article , the authors discuss several novel theranostic systems and smart nanoparticles, their mechanism of action, and their modifications with time, and explain their relevance and market scope in the current era.
Abstract: The alarming increase in the number of breast cancer patients worldwide and the increasing death rate indicate that the traditional and current medicines are insufficient to fight against it. The onset of chemo- and radioresistances and cancer stem cell-based recurrence make this problem harder, and this hour needs a novel treatment approach. Competent nanoparticle-based accurate drug delivery and cancer nanotheranostics like photothermal therapy, photodynamic therapy, chemodynamic therapy, and sonodynamic therapy can be the key to solving this problem due to their unique characteristics. These innovative formulations can be a better cargo with fewer side effects than the standard chemotherapy and can eliminate the stability problems associated with cancer immunotherapy. The nanotheranostic systems can kill the tumor cells and the resistant breast cancer stem cells by novel mechanisms like local hyperthermia and reactive oxygen species and prevent tumor recurrence. These theranostic systems can also combine with chemotherapy or immunotherapy approaches. These combining approaches can be the future of anticancer therapy, especially to overcome the breast cancer stem cells mediated chemo- and radioresistances. This review paper discusses several novel theranostic systems and smart nanoparticles, their mechanism of action, and their modifications with time. It explains their relevance and market scope in the current era. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
2 citations
TL;DR: In this paper , a review of the critical research progress of silk fibroin microneedles since their inception, analyzes in detail the structure and properties of Silk Fibroin, the types of Silk-Fibroin microdroneedles, drug delivery applications and clinical trials, and summarizes the future development trend in this field.
Abstract: Microneedles are a patient-friendly technique for delivering drugs to the site of action in place of traditional oral and injectable administration. Silk fibroin represents an interesting polymeric biomaterial because of its mechanical properties, thermal stability, biocompatibility and possibility of control via genetic engineering. This review focuses on the critical research progress of silk fibroin microneedles since their inception, analyzes in detail the structure and properties of silk fibroin, the types of silk fibroin microneedles, drug delivery applications and clinical trials, and summarizes the future development trend in this field. It also proposes the future research direction of silk fibroin microneedles, including increasing drug loading doses and enriching drug loading types as well as exploring silk fibroin microneedles with stimulation-responsive drug release functions. The safety and effectiveness of silk fibroin microneedles should be further verified in clinical trials at different stages.
2 citations
TL;DR: In this article , the authors used human placental extracellular matrix (ECM) derived from the placenta, sodium-alginate and gelatin to prepare a printable bioink biomimicking natural skin.
Abstract: Extracellular matrix (ECM)-based bioinks has attracted much attention in recent years for 3D printing of native-like tissue constructs. Due to organ unavailability, human placental ECM can be an alternative source for the construction of 3D print composite scaffolds for the treatment of deep wounds. In this study, we use different concentrations (1.5%, 3% and 5%w/v) of ECM derived from the placenta, sodium-alginate and gelatin to prepare a printable bioink biomimicking natural skin. The printed hydrogels' morphology, physical structure, mechanical behavior, biocompatibility, and angiogenic property are investigated. The optimized ECM (5%w/v) 3D printed scaffold is applied on full-thickness wounds created in a mouse model. Due to their unique native-like structure, the ECM-based scaffolds provide a non-cytotoxic microenvironment for cell adhesion, infiltration, angiogenesis, and proliferation. In contrast, they do not show any sign of immune response to the host. Notably, the biodegradation, swelling rate, mechanical property, cell adhesion and angiogenesis properties increase with the increase of ECM concentrations in the construct. The ECM 3D printed scaffold implanted into deep wounds increases granulation tissue formation, angiogenesis, and re-epithelialization due to the presence of ECM components in the construct, when compared with printed scaffold with no ECM and no treatment wound. Overall, our findings demonstrate that the 5% ECM 3D scaffold supports the best deep wound regeneration in vivo, produces a skin replacement with a cellular structure comparable to native skin.
1 citations
TL;DR: In this article , the influence of fiber diameter on stem cell behaviors is precisely and comprehensively investigated based on eliminating the undesired "interference" cell adhesions in a controllable way.
Abstract: Abstract Due to the innate extracellular matrix mimicking features, fibrous materials exhibited great application potential in biomedicine. In developing excellent fibrous biomaterial, it is essential to reveal the corresponding inherent fiber features’ effects on cell behaviors. Due to the inevitable ‘interference’ cell adhesions to the background or between adjacent fibers, it is difficult to precisely reveal the inherent fiber diameter effect on cell behaviors by using a traditional fiber mat. A single-layer and parallel-arranged polycaprolactone fiber pattern platform with an excellent non-fouling background is designed and constructed herein. In this unique material platform, the ‘interference’ cell adhesions through interspace between fibers to the environment could be effectively ruled out by the non-fouling background. The ‘interference’ cell adhesions between adjacent fibers could also be excluded from the sparsely arranged (SA) fiber patterns. The influence of fiber diameter on stem cell behaviors is precisely and comprehensively investigated based on eliminating the undesired ‘interference’ cell adhesions in a controllable way. On the SA fiber patterns, small diameter fiber (SA-D1, D1 means 1 μm in diameter) may seriously restrict cell proliferation and osteogenesis when compared to the middle (SA-D8) and large (SA-D56) ones and SA-D8 shows the optimal osteogenesis enhancement effect. At the same time, the cells present similar proliferation ability and even the highest osteogenic ability on the densely arranged (DA) fiber patterns with small diameter fiber (DA-D1) when compared to the middle (DA-D8) and large (DA-D56) ones. The ‘interference’ cell adhesion between adjacent fibers under dense fiber arrangement may be the main reason for inducing these different cell behavior trends along with fiber diameters. Related results and comparisons have illustrated the effects of fiber diameter on stem cell behaviors more precisely and objectively, thus providing valuable reference and guidance for developing effective fibrous biomaterials.
TL;DR: In this article , a 3D breast cancer model was developed based on enzymatically crosslinked silk fibroin (eSF) hydrogels, with and without human mammary fibroblasts.
Abstract: Breast cancer is still the leading cause of women's death due to relapse and metastasis. In vitro tumor models are considered reliable tools for drug screening and understanding cancer‐driving mechanisms due to the possibility of mimicking tumor heterogeneity. Herein, a 3D breast cancer model (3D‐BCM) is developed based on enzymatically‐crosslinked silk fibroin (eSF) hydrogels. Human MCF7 breast cancer cells are encapsulated into eSF hydrogels, with and without human mammary fibroblasts. The spontaneously occurring conformational change from random coil to β‐sheet is correlated with increased eSF hydrogels’ stiffness over time. Moreover, mechanical properties analysis confirms that the cells can modify the stiffness of the hydrogels, mimicking the microenvironment stiffening occurring in vivo. Fibroblasts support cancer cells growth and assembly in the eSF hydrogels up to 14 days of culture. Co‐cultured 3D‐BCM exhibits an upregulated expression of genes related to extracellular matrix remodeling and fibroblast activation. The 3D‐BCM is subjected to doxorubicin and paclitaxel treatments, showing differential drug response. Overall, these results suggest that the co‐culture of breast cancer cells and fibroblasts in eSF hydrogels allow the development of a mimetic in vitro platform to study cancer progression. This opens up new research avenues to investigate novel molecular targets for anti‐cancer therapy.
TL;DR: In this paper , an electro-responsive insulin delivery system based on thiolated silk fibroin was proposed, where the disulfide cross-linking points in TSF were reduced and broken to form sulfhydryl groups under electrification, which led to the increase of microneedle swelling degree and promoted insulin release.
TL;DR: In this paper , a review summarizes the studies that utilized different surfactants to control the formation, structure, and properties of molecular and silk fibroin gels, which are interfacial and non-interfacial effects.
TL;DR: In this paper , the authors developed bilayered porous silk fibroin scaffolds and tested their effect on thymic epithelial cell (TEC) co-cultures.
Abstract: The thymus coordinates the development and selection of T cells. It is structured into two main compartments: the cortex and the medulla. The replication of such complex 3D environment has been challenged by bioengineering approaches. Nevertheless, the effect of the scaffold microstructure on thymic epithelial cell (TEC) cultures has not been deeply investigated. Here, we developed bilayered porous silk fibroin scaffolds and tested their effect on TEC co-cultures. The small and large pore scaffolds presented a mean pore size of 84.33 ± 21.51 μm and 194.90 ± 61.38 μm, respectively. The highly porous bilayered scaffolds presented a high water absorption and water content (> 94 %), together with mechanical properties in the range of the native tissue. TEC (i.e., medullary (mTEC) and cortical (cTEC) cell lines) proliferation is increased in scaffolds with larger pores. The co-culture of both TEC lines in the bilayered porous silk scaffolds presents enhanced cell proliferation and metabolic activity when compared with mTEC in single culture. Also, when the co-culture occurred with cTEC in the small pores layer and mTEC in the large pores layer, a 9.2- and 18.9-fold increase in Foxn1 and Icam1 gene expression in cTEC is evident. These results suggest that scaffold microstructure and the co-culture influence TEC's behaviour. Bilayered silk scaffolds with adjusted microstructure are a valid alternative for TEC culture, having possible applications in advanced thymus bioengineering strategies.
TL;DR: In this paper , a fluorinated pluronic (FP127) was synthesized and employed to functionalize the surface of mulberry leaf-derived nanoparticles (MLNs) loading with resveratrol nanocrystals (RNs).
Abstract: The therapeutic outcomes of conventional oral medications against ulcerative colitis (UC) are restricted by inefficient drug delivery to the colitis mucosa and weak capacity to modulate the inflammatory microenvironment. Herein, a fluorinated pluronic (FP127) was synthesized and employed to functionalize the surface of mulberry leaf-derived nanoparticles (MLNs) loading with resveratrol nanocrystals (RNs). The obtained FP127@RN-MLNs possessed exosome-like morphologies, desirable particle sizes (around 171.4 nm), and negatively charged surfaces (−14.8 mV). The introduction of FP127 to RN-MLNs greatly improved their stability in the colon and promoted their mucus infiltration and mucosal penetration capacities due to the unique fluorine effect. These MLNs could efficiently be internalized by colon epithelial cells and macrophages, reconstruct disrupted epithelial barriers, alleviate oxidative stress, provoke macrophage polarization to M2 phenotype, and down-regulate inflammatory responses. Importantly, in vivo studies based on chronic and acute UC mouse models demonstrated that oral administration of chitosan/alginate hydrogel-embedding FP127@RN-MLNs achieved substantially improved therapeutic efficacies compared with nonfluorinated MLNs and a first-line UC drug (dexamethasone), as evidenced by decreased colonic and systemic inflammation, integrated colonic tight junctions, and intestinal microbiota balance. This study brings new insights into the facile construction of a natural, versatile nanoplatform for oral treatment of UC without adverse effects.
TL;DR: In this article , the authors proposed a novel approach for early cancer diagnosis and treatment using tissue-engineered cancer traps on a chip, which can be used for liquid biopsy and the early detection of circulating tumor cells and other tumor-derived material.
Abstract: Cancer continues to be a major global health issue causing millions of deaths annually. While traditional therapeutic methods may be effective in many cases, they may not be suitable for highly metastatic cancers. Moreover, the late detection of tumors, when they have already spread and are harder to treat, further exacerbates the challenge in managing this disease. As a result, there is a growing interest in developing complementary tissue-engineered approaches for early cancer diagnosis and treatment to enhance patient recovery. Bioengineered cancer traps have gained significant attention due to their efficacy and ease of use. These trapping systems employ (bio)chemical and mechanical strategies to selectively capture and limit the spread of cancer cells, leading to their eradication from the body. Furthermore, when integrated into microfluidic devices, these cancer traps-on-a-chip can be used for liquid biopsy and the early detection of circulating tumor cells and other tumor-derived material, allowing for precision medicine treatments. Herein, this innovative approach to cancer theranostics, including its mechanism of action, current stage of development, and potential advantages and limitations is discussed.
TL;DR: In this article , the authors used polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery in diabetic rats, showing that the insulin inside the microneedle was released as the blood glucose concentration increased.
Abstract: Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis of MNs’ appearance and morphology revealed that the MNs were well arranged and formed an array with 0.5 mm pitch, and the length of single MNs is approximately 430 μm. The average breaking force of an MN is above 1.25 N, which guarantees that it can pierce the skin quickly and reach the dermis. Cationized SF MNs are pH-responsive. MNs dissolution rate increases as pH decreases and the rate of insulin release are accelerated. The swelling rate reached 223% at pH = 4, while only 172% at pH = 9. After adding glucose oxidase, cationized SF MNs are glucose-responsive. As the glucose concentration increases, the pH inside the MNs decreases, the MNs’ pore size increases, and the insulin release rate accelerates. In vivo experiments demonstrated that in normal Sprague Dawley (SD) rats, the amount of insulin released within the SF MNs was significantly smaller than that in diabetic rats. Before feeding, the blood glucose (BG) of diabetic rats in the injection group decreased rapidly to 6.9 mmol/L, and the diabetic rats in the patch group gradually reduced to 11.7 mmol/L. After feeding, the BG of diabetic rats in the injection group increased rapidly to 33.1 mmol/L and decreased slowly, while the diabetic rats in the patch group increased first to 21.7 mmol/L and then decreased to 15.3 mmol/L at 6 h. This demonstrated that the insulin inside the microneedle was released as the blood glucose concentration increased. Cationized SF MNs are expected to replace subcutaneous injections of insulin as a new modality for diabetes treatment.