Exploring gellan gum-based hydrogels for regenerating human embryonic stem cells in age-related macular degeneration therapy: A literature review.

Age-related macular degeneration (AMD) is a progressive ocular disease marked by the deterioration of retinal photoreceptor cells, leading to central vision decline, predominantly affecting the elderly population worldwide. Current treatment modalities, such as anti-VEGF agents, laser therapy, and photodynamic therapy, aim to manage the condition, with emerging strategies like stem cell replacement therapy showing promise. However, challenges like immune rejection and cell survival hinder the efficacy of stem cell interventions. Regenerative medicine faces obstacles in maximizing stem cell potential due to limitations in mimicking the dynamic cues of the extracellular matrix (ECM) crucial for guiding stem cell behaviour. Innovative biomaterials like gellan gum hydrogels offer tailored microenvironments conducive to enhancing stem cell culture efficacy and tissue regeneration. Gellan gum-based hydrogels, renowned for biocompatibility and customizable mechanical properties, provide crucial support for cell viability, differentiation, and controlled release of therapeutic factors, making them an ideal platform for culturing human embryonic stem cells (hESCs). These hydrogels mimic native tissue mechanics, promoting optimal hESC differentiation while minimizing immune responses and facilitating localized delivery. This review explores the potential of Gellan Gum-Based Hydrogels in regenerative AMD therapy, emphasizing their role in enhancing hESC regeneration and addressing current status, treatment limitations, and future directions.

Prediction of osteoporosis using MRI and CT scans with unimodal and multimodal deep-learning models.

PURPOSE: Osteoporosis is the systematic degeneration of the human skeleton, with consequences ranging from a reduced quality of life to mortality. Therefore, the prediction of osteoporosis reduces risks and supports patients in taking precautions. Deep-learning and specific models achieve highly accurate results using different imaging modalities. The primary purpose of this research was to develop unimodal and multimodal deep-learning-based diagnostic models to predict bone mineral loss of the lumbar vertebrae using magnetic resonance (MR) and computed tomography (CT) imaging. METHODS: Patients who received both lumbar dual-energy X-ray absorptiometry (DEXA) and MRI (n = 120) or CT (n = 100) examinations were included in this study. Unimodal and multimodal convolutional neural networks (CNNs) with dual blocks were proposed to predict osteoporosis using lumbar vertebrae MR and CT examinations in separate and combined datasets. Bone mineral density values obtained by DEXA were used as reference data. The proposed models were compared with a CNN model and six benchmark pre-trained deep-learning models. RESULTS: The proposed unimodal model obtained 96.54%, 98.84%, and 96.76% balanced accuracy for MRI, CT, and combined datasets, respectively, while the multimodal model achieved 98.90% balanced accuracy in 5-fold cross-validation experiments. Furthermore, the models obtained 95.68%-97.91% accuracy with a hold-out validation dataset. In addition, comparative experiments demonstrated that the proposed models yielded superior results by providing more effective feature extraction in dual blocks to predict osteoporosis. CONCLUSION: This study demonstrated that osteoporosis was accurately predicted by the proposed models using both MR and CT images, and a multimodal approach improved the prediction of osteoporosis. With further research involving prospective studies with a larger number of patients, there may be an opportunity to implement these technologies into clinical practice.

Preparation characterization and blood compatibility studies of silk fibroin/gelatin/curcumin injectable hydrogels.

BACKGROUND: Hydrogel is a three-dimensional structure that has the potential to absorb and retain water within the mesh of its porous network structure. Currently hydrogels made from natural biopolymers are preferred in the discipline of biomedical applications because of their blood compatibility, adhesion of platelets and protein binding, ease of administration and delivery of ingredients to the place of action. OBJECTIVE: The aim of this work was to prepare a hydrogel from natural biopolymers and evaluate its blood compatibility, swelling nature, prolonged degradation and morphological features in order to further recommend its clinical use. METHODS: To prepare hydrogels, different combinations of gelatin, dialyzed SF, curcumin and N, N methylene bisacrylamide (MBA) were evenly mixed on a magnetic stirrer. After an hour of the gelation process it was kept in a refrigerator at 4 °C. For the characterization and biocompatibility studies of hydrogel, the swelling test and biodegradation analysis, SEM, FTIR, in vitro coagulation tests, total serum albumin and cholesterol level analysis were applied. RESULTS: Injectable hydrogels were successfully made with significantly correlated combinations of polymers. The analysis of physiochemical biocompatibility studies and morphological characterization were done effectively. CONCLUSION: The results of the study indicate that hydrogels made from natural biopolymers are a potential source and suitable matrices with excellent biocompatible nature acting as a useful device in delivering drugs.

Intravitreal Injectable Hydrogels for Sustained Drug Delivery in Glaucoma Treatment and Therapy.

Glaucoma is extensively treated with topical eye drops containing drugs. However, the retention time of the loaded drugs and the in vivo bioavailability of the drugs are highly influenced before reaching the targeted area sufficiently, due to physiological and anatomical barriers of the eye, such as rapid nasolacrimal drainage. Poor intraocular penetration and frequent administration may also cause ocular cytotoxicity. A novel approach to overcome these drawbacks is the use of injectable hydrogels administered intravitreously for sustained drug delivery to the target site. These injectable hydrogels are used as nanocarriers to intimately interact with specific diseased ocular tissues to increase the therapeutic efficacy and drug bioavailability of the anti-glaucomic drugs. The human eye is very delicate, and is sensitive to contact with any foreign body material. However, natural biopolymers are non-reactive, biocompatible, biodegradable, and lack immunogenic and inflammatory responses to the host whenever they are incorporated in drug delivery systems. These favorable biomaterial properties have made them widely applicable in biomedical applications, with minimal adversity. This review highlights the importance of using natural biopolymer-based intravitreal hydrogel drug delivery systems for glaucoma treatment over conventional methods.

In Vitro MCF-7 Cells Apoptosis Analysis of Carboplatin Loaded Silk Fibroin Particles.

Breast cancer ranks as the fifth leading cause of death worldwide. Chemotherapy is commonly used directly or as neo-adjuvant therapy for the management of breast cancer with its attendant adverse effects, underscoring the need to develop biocompatible bioactive compounds for pharmacological applications. The aim of this study is to encapsulate carboplatin (CP) with silk fibroin protein (SF) by using an ionic gelation method as a drug carrier system and assess the apoptotic effect on MCF-7 breast cancer cells during in vitro studies. The characterization of silk fibroin encapsulated carboplatin (SFCP) microparticles was analyzed by FTIR spectrophotometer, SEM, Mastersizer, and biodegradation methods. The encapsulation efficiency and release profile of SFCP microparticles were analyzed by an indirect UV-Vis spectrophotometric method. An apoptotic screening of MCF-7 cells was carried out with 10-200 µg/mL CP loaded SFCP, which were cultured for 24, 48, and 72 h. Data were analyzed using the Student's t test and analysis of variance. FTIR and drug release studies confirmed an interaction of silk fibroin with the carboplatin moiety. SFCP showed successful encapsulation of the carboplatin moiety. Apoptotic screening showed a dose dependent increase in absorbance, indicating significant cell death (p < 0.05). Thus, the direct apoptotic effect of SFCP microparticles on MCF-7 was confirmed.

Alzheimer's Disease Targeted Nano-Based Drug Delivery Systems.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer's disease and their implications in therapy is discussed.

The chondrocyte cell proliferation of a chitosan/silk fibroin/egg shell membrane hydrogels.

Articular cartilage is a poorly cellularized, non-vascularized connective tissue that undergoes alterations due to trauma and osteoarthritis. Tissue engineering strategies involving the combination of cells, biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. The aim of this study was to design Chitosan/Silk Fibroin/Egg Shell Membrane (CHI/SF/ESM) hydrogels and analyse the cell proliferation activity of human chondrocyte cells. The FTIR spectrophotometer, XRD analysis, ICP-MS, SEM analysis, swelling kinetics and biodegradation tests with protease enzyme, and antibacterial activity test with Escherichia coli, Candida albicans have been used for characterization of hydrogels. CHI/SF/ESM hydrogel structures, and chemical homogeneity of the ECM was well-reproduced. Human articular chondrocytes were seeded on hydrogels and cultured up to 2 weeks under the standard culture conditions. The attachment and cell growth of chondrocytes were examined by phase contrast microscopy and by MTT assay at 24 h, 72 h and 7 days. The hydrogel supported better adhesion, growth and differentiation of chondrocyte cells under standard culture conditions. The results obtained have suggested that, CHI/SF/ESM hydrogels can potentially function as a promising cartilage substitute for tissue engineering application.

Chitosan-graft-poly(N-hydroxy ethyl acrylamide) copolymers: Synthesis, characterization and preliminary blood compatibility in vitro.

Poly(N-hydroxy ethyl acrylamide) was grafted onto chitosan in aqueous acidic medium using potassium per sulphate initiator to obtain polymer surfaces with blood compatibility for potential biomedical applications. Thermally cross-linked products were obtained upon drying at 60 °C overnight. Chemically cross-linked films were prepared using methylene bis acrylamide (MBA) cross-linker. The products were characterized by FTIR, XRD and SEM analyses. Protein adsorption onto the film surfaces gave, on the average, 30% bovine serum albumin (BSA) and 10% human serum albumin (HSA) removal from aqueous solution, in vitro. Blood compatibility was evaluated with respect to activated prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet adhesion. PT and APTT values remained within normal ranges after blood-polymer contact, with chitosan-graft-polyHEAA films, in vitro. Chitosan-graft-MBA or chitosan-graft-(polyHEAA;MBA), and blank chitosan films produced higher PT and APTT values under similar experimental conditions with chitosan-graft-polyHEAA films, exhibiting blood anticoagulant activity. SEM pictures taken before and after contact with blood sample did not reveal any significant blood component adhesion on the chitosan-graft-(polyHEAA;MBA) film surface contrary to the observation made on the blank chitosan film.

The Use of Scaffolds in Cartilage Regeneration.

Scaffolds are important tools in tissue engineering and play a unique role in tissue regeneration and repair of damaged tissues. A variety of natural, synthetic, and composite scaffold types can be used in cartilage tissue engineering. The limited capability of cartilage to repair itself has always been a problem during recovery from damage. The success of cartilage regeneration is dependent on a couple of factors, but the basic properties of scaffolds are biocompatibility, degradability under physiological conditions, and structural support for cell attachment. In this review, we summarize the use of different scaffold types in cartilage regeneration.

The Wonders of Silk Fibroin Biomaterials in the Treatment of Breast Cancer.

Breast cancer has continued to be a cause of increasing morbidity and mortality in women, being the most common cause of cancer-related deaths among them. Its management using chemotherapy is continually plagued with problems of systemic toxicity, lack of compliance by patients, and inadequate targeting of cancer cells. The future of breast cancer chemotherapy will likely involve the use of biocompatible high cell-targeting capacity drug-delivery vehicles like silk fibroin to ameliorate these problems. The utilization of silk fibroin nanoparticles to deliver cytotoxic drugs provides specificity, optimal entrapment, improved therapeutic index, and maximal breast cancer cell toxicity with minimal or no collateral damage to surrounding normal cells. The silk fibroin obtained from the cocoon of the Bombyx morii worm is processed and degummed to remove the sericin component; it is then made into nanoparticles utilizing the desolvation, ionic gelation, or electrospray method. It is then loaded with an appropriate chemotherapeutic drug (e.g., carboplatin), and characterization is performed using physico-chemical methods such as fourier-transform infrared spectroscopy, dynamic light scattering, or transmission electron microscopy. The nanoparticles are then tested for cytoxicity, and the induction of apoptosis on breast cancer cell lines MC-7 (Her2-) and MDA-MB-453 (Her2+). Toxicity and apoptosis are assessed using the MTT assay and ELISA methods, respectively. Silk fibroin has been demonstrated in various studies to be a very useful tool in specific active or passive drug delivery to target cancer cells, thus ensuring a maximum destruction and minimum damage to normal surrounding cells, which decreases systemic toxicity and enhances drug efficacy.

Silk fibroin as a non-thrombogenic biomaterial.

Silk fibroin (SF), is a very attractive protein-polymer, being processed into a variety of formats to match structural and morphological features for specific biomedical applications. The aim of the present work is to investigate blood compatibility of two forms, films and scaffolds, of silk fibroin-N,N' methylene bisacrylamide (MBA) prepared by using blend solutions of the two components. Biofilms were prepared under UV-irradiation while scaffolds were prepared via freeze-drying technique at -30°C and -80°C, respectively. Swelling, biodegradation tests with protease enzyme, FTIR, SEM, XRD analyses were applied to characterize the biomaterials. The results indicated that, the presence of the crosslinker (MBA) in the scaffold and biofilm aids the formation of ordered structure. The pore size and biodegradability can be controllable by the amount of crosslinker. The anticoagulant activity was evaluated using prothrombin time (PT), activated partial thromboplastin time (APTT). The in-vitro coagulation test and platelet adhesion test analyses indicated that the modified scaffolds and biofilms exhibited better hemocompatibility in comparison with pure silk fibroin. These results demostrated that the silk fibrion-N,N' methylene bisacrylamide biofilms and blended scaffolds have potential applications as blood contact device.

PEG-calf thymus DNA interactions: conformational, morphological and spectroscopic thermal studies.

The main aim of this study is to provide understanding for the interaction modes and the binding affinity based on the study of PEG 400 that binds to ctDNA. The effects of the PEG-400-to-ctDNA ratio, pH, incubation time and thermal stability of ctDNA on PEG-ctDNA biocomplex formation were studied. UV-vis-NIR absorption analysis indicated that PEG forms a complex with ctDNA via a mechanism other than intercalation. The results of thermal denaturation studies showed that the PEG-ctDNA biocomplex helix was stabilised, with a resulting increase in the PEG-ctDNA melting temperature. FTIR analysis indicated that the PEG binds to ctDNA through weak to moderately strong hydrophilic and hydrophobic interactions with the base pairs of ctDNA. TEM micrographs showed that the addition of PEG to ctDNA caused ctDNA to condense with PEG molecules into an irregular aggregate structure. These results demonstrate that the PEG-ctDNA biocomplex has potential applications in biomedical sciences.

Synthesis and characterization of noncytotoxic and biodegradable polymethacrylates-grafted chitosan gels.

Poly(methacrylates), namely 2-hydroxy ethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EGDMA) and triethylene glycol dimethacrylate (TEGDMA) were grafted onto chitosan by using ceric ammonium nitrate as a redox initiator. Semi-IPN gels of chitosan-graft-poly(HEMA)-graft-poly(EGDMA) and chitosan-graft-poly(HEMA)-graft-poly(TEGDMA) were obtained. The grafting conditions were optimized with respect to monomer concentrations. The products were characterized by TGA, FTIR, XRD and SEM techniques. The solubility of the grafted products in aqueous medium decreased with increasing grafting percentage. The insoluble gels exhibited a highly pH sensitive swelling behaviour. TGA thermograms showed that poly(HEMA)/poly(TEGDMA)-grafted product is much more stable than poly(HEMA)/poly(EGDMA)-grafted product showing that TEGDMA is a more effective crosslinker than EGDMA. According to XRD analysis TEGDMA has a higher tendency to form ordered structures than EGDMA as it is capable of chain folding. The results of cytotoxicity studies revealed that the methacrylate-grafted chitosans were noncytotoxic and good candidates for biomedical applications.