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1.
ACS Nano ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39356827

ABSTRACT

Diabetic foot ulcers (DFUs) are a significant challenge in the clinical care of diabetic patients, often necessitating limb amputation and compromising the quality of life and life expectancy of this cohort. Minimally invasive therapies, such as modular scaffolds, are at the forefront of current DFU treatment, offering an efficient approach for administering therapeutics that accelerate tissue repair and regeneration. In this study, we report a facile method for fabricating granular nanofibrous microspheres (NMs) with predesigned structures and porosities. The proposed technology combines electrospinning and electrospraying to develop a therapeutic option for DFUs. Specifically, porous NMs were constructed using electrospun poly(lactic-co-glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin cross-linking. These NMs demonstrated enhanced cell adhesion to human dermal fibroblasts (HDF) during an in vitro cytocompatibility assessment. Notably, porous NMs displayed superior performance owing to their interconnected pores compared to nonporous NMs. Cell-laden NMs demonstrated higher Young's modulus values than NMs without loaded cells, suggesting improved material resiliency attributed to the reinforcement of cells and their secreted extracellular matrix. Dynamic injection studies on cell-laden NMs further elucidated their capacity to safeguard loaded cells under pressure. In addition, porous NMs promoted host cell infiltration, neovascularization, and re-epithelialization in a diabetic mouse wound model, signifying their effectiveness in healing diabetic wounds. Taken together, porous NMs hold significant potential as minimally invasive, injectable treatments that effectively promote tissue integration and regeneration.

2.
ACS Nano ; 18(40): 27764-27781, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39342648

ABSTRACT

Obesity is defined as chronic, low-grade inflammation within specific tissues. Given the escalating prevalence of obesity among individuals of all ages, obesity has reached epidemic proportions, posing an important public health challenge. Despite significant advancements in treating obesity, conventional approaches remain largely ineffective or involve severe side effects, thus underscoring the pressing need to explore and develop treatment approaches. Targeted and local immunomodulation using nanoparticles (NPs) can influence fat production and utilization processes. Statins, known for their anti-inflammatory properties, show the potential for mitigating obesity-related inflammation. A localized delivery option offers several advantages over oral and parenteral delivery methods. Here, we developed simvastatin (Sim) encapsulated within PLGA NPs (Sim-NP) for localized delivery of Sim to adipose tissues (ATs) for immunomodulation to treat obesity. In vitro experiments revealed the strong anti-inflammatory effects of Sim-NPs, which resulted in enhanced modulation of macrophage (MΦ) polarization and induction of AT browning. We then extended our investigation to an in vivo mouse model of high-fat-diet (HFD)-induced obesity. Sim-NP administration led to the controlled release of Sim within AT, directly impacting MΦ activity and inducing AT browning while inducing weight loss. Our findings demonstrated that Sim-NP administration effectively inhibited the progression of obesity-related inflammation, controlled white fat production, and enhanced AT modulation. These results highlight the potential of Sim-NP as a potent nanotherapy for treating obesity by modulating the immune system.


Subject(s)
Macrophages , Mice, Inbred C57BL , Nanoparticles , Obesity , Simvastatin , Animals , Mice , Obesity/drug therapy , Obesity/pathology , Macrophages/drug effects , Macrophages/metabolism , Nanoparticles/chemistry , Simvastatin/pharmacology , Simvastatin/chemistry , Inflammation/drug therapy , Inflammation/pathology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Male , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry
3.
Antibodies (Basel) ; 13(3)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39189232

ABSTRACT

The development of de novo donor-specific HLA antibodies (dnDSAs) following solid organ transplantation is considered a major risk factor for poor long-term allograft outcomes. The prediction of dnDSA development is a boon to transplant recipients, yet the assessment of allo-HLA immunogenicity remains imprecise. Despite the recent technological advances, a comprehensive evaluation of allo-HLA immunogenicity, which includes both B and T cell allorecognition, is still warranted. Recent studies have proposed using mismatched HLA epitopes (antibody and T cell) as a prognostic biomarker for humoral alloimmunity. However, the identification of immunogenic HLA mismatches has not progressed despite significant improvements in the identification of permissible mismatches. Certainly, the prediction of dnDSA development may benefit permissible HLA mismatched organ transplantations, personalized immunosuppression, and clinical trial design. However, characteristics that go beyond the listing of mismatched HLA antibody epitopes and T cell epitopes, such as the generation of HLA T cell epitope repertoires, recipient's HLA class II phenotype, and immunosuppressive regiments, are required for the precise assessment of allo-HLA immunogenicity.

4.
Small ; : e2403560, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39212623

ABSTRACT

Drug toxicity assays using conventional 2D static cultures and animal studies have limitations preventing the translation of potential drugs to the clinic. The recent development of organs-on-a-chip platforms provides promising alternatives for drug toxicity/screening assays. However, most studies conducted with these platforms only utilize single endpoint results, which do not provide real-time/ near real-time information. Here, a versatile technology is presented that integrates a 3D liver-on-a-chip with a label-free photonic crystal-total internal reflection (PC-TIR) biosensor for rapid and continuous monitoring of the status of cells. This technology can detect drug-induced liver toxicity by continuously monitoring the secretion rates and levels of albumin and glutathione S-transferase α (GST-α) of a 3D liver on-a-chip model treated with Doxorubicin. The PC-TIR biosensor is based on a one-step antibody functionalization with high specificity and a detection range of 21.7 ng mL-1 to 7.83 x 103 ng mL-1 for albumin and 2.20 ng mL-1 to 7.94 x 102 ng mL-1 for GST-α. This approach provides critical advantages for the early detection of drug toxicity and improved temporal resolution to capture transient drug effects. The proposed proof-of-concept study introduces a scalable and efficient plug-in solution for organ-on-a-chip technologies, advancing drug development and in vitro testing methods by enabling timely and accurate toxicity assessments.

5.
Acta Biomater ; 183: 89-100, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38801867

ABSTRACT

Self-assembling peptide-based hydrogels have become a highly attractive scaffold for three-dimensional (3D) in vitro disease modeling as they provide a way to create tunable matrices that can resemble the extracellular matrix (ECM) of various microenvironments. Alzheimer's disease (AD) is an exceptionally complex neurodegenerative condition; however, our understanding has advanced due to the transition from two-dimensional (2D) to 3D in vitro modeling. Nonetheless, there is a current gap in knowledge regarding the role of amyloid structures, and previously developed models found long-term difficulty in creating an appropriate model involving the ECM and amyloid aggregates. In this report, we propose a multi-component self-assembling peptide-based hydrogel scaffold to mimic the amyloid-beta (ß) containing microenvironment. Characterization of the amyloid-ß-mimicking hydrogel (Col-HAMA-FF) reveals the formation of ß-sheet structures as a result of the self-assembling properties of phenylalanine (Phe, F) through π-π stacking of the residues, thus mimicking the amyloid-ß protein nanostructures. We investigated the effect of the amyloid-ß-mimicking microenvironment on healthy neuronal progenitor cells (NPCs) compared to a natural-mimicking matrix (Col-HAMA). Our results demonstrated higher levels of neuroinflammation and apoptosis markers when NPCs were cultured in the amyloid-like matrix compared to a natural brain matrix. Here, we provided insights into the impact of amyloid-like structures on NPC phenotypes and behaviors. This foundational work, before progressing to more complex plaque models, provides a promising scaffold for future investigations on AD mechanisms and drug testing. STATEMENT OF SIGNIFICANCE: In this study, we engineered two multi-component hydrogels: one to mimic the natural extracellular matrix (ECM) of the brain and one to resemble an amyloid-like microenvironment using a self-assembling peptide hydrogel. The self-assembling peptide mimics ß-amyloid fibrils seen in amyloid-ß protein aggregates. We report on the culture of neuronal progenitor cells within the amyloid-mimicking ECM scaffold to study the impact through marker expressions related to inflammation and DNA damage. This foundational work, before progressing to more complex plaque models, offers a promising scaffold for future investigations on AD mechanisms and drug testing.


Subject(s)
Amyloid beta-Peptides , Hydrogels , Neural Stem Cells , Hydrogels/chemistry , Hydrogels/pharmacology , Amyloid beta-Peptides/metabolism , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Neural Stem Cells/drug effects , Phenotype , Humans , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Animals
6.
Int J Biol Macromol ; 267(Pt 2): 131666, 2024 May.
Article in English | MEDLINE | ID: mdl-38636755

ABSTRACT

Natural Rubber Latex (NRL) has shown to be a promising biomaterial for use as a drug delivery system to release various bioactive compounds. It is cost-effective, easy to handle, biocompatible, and exhibits pro-angiogenic and pro-healing properties for both soft and hard tissues. NRL releases compounds following burst and sustained release kinetics, exhibiting first-order release kinetics. Moreover, its pore density can be adjusted for tailored kinetics profiles. In addition, biotechnological applications of NRL in amblyopia, smart mattresses, and neovaginoplasty have demonstrated success. This comprehensive review explores NRL's diverse applications in biotechnology and biomedicine, addressing challenges in translating research into clinical practice. Organized into eight sections, the review emphasizes NRL's potential in wound healing, drug delivery, and metallic nanoparticle synthesis. It also addresses the challenges in enhancing NRL's physical properties and discusses its interactions with the human immune system. Furthermore, examines NRL's potential in creating wearable medical devices and biosensors for neurological disorders. To fully explore NRL's potential in addressing important medical conditions, we emphasize throughout this review the importance of interdisciplinary research and collaboration. In conclusion, this review advances our understanding of NRL's role in biomedical and biotechnological applications, offering insights into its diverse applications and promising opportunities for future development.


Subject(s)
Biocompatible Materials , Drug Delivery Systems , Latex , Regenerative Medicine , Rubber , Humans , Biocompatible Materials/chemistry , Latex/chemistry , Regenerative Medicine/methods , Rubber/chemistry , Wound Healing/drug effects
7.
ACS Sens ; 9(5): 2334-2345, 2024 05 24.
Article in English | MEDLINE | ID: mdl-38639453

ABSTRACT

Noninvasive monitoring of biofabricated tissues during the biomanufacturing process is needed to obtain reproducible, healthy, and functional tissues. Measuring the levels of biomarkers secreted from tissues is a promising strategy to understand the status of tissues during biofabrication. Continuous and real-time information from cultivated tissues enables users to achieve scalable manufacturing. Label-free biosensors are promising candidates for detecting cell secretomes since they can be noninvasive and do not require labor-intensive processes such as cell lysing. Moreover, most conventional monitoring techniques are single-use, conducted at the end of the fabrication process, and, challengingly, are not permissive to in-line and continual detection. To address these challenges, we developed a noninvasive and continual monitoring platform to evaluate the status of cells during the biofabrication process, with a particular focus on monitoring the transient processes that stem cells go through during in vitro differentiation over extended periods. We designed and evaluated a reusable electrochemical immunosensor with the capacity for detecting trace amounts of secreted osteogenic markers, such as osteopontin (OPN). The sensor has a low limit of detection (LOD), high sensitivity, and outstanding selectivity in complex biological media. We used this OPN immunosensor to continuously monitor on-chip osteogenesis of human mesenchymal stem cells (hMSCs) cultured 2D and 3D hydrogel constructs inside a microfluidic bioreactor for more than a month and were able to observe changing levels of OPN secretion during culture. The proposed platform can potentially be adopted for monitoring a variety of biological applications and further developed into a fully automated system for applications in advanced cellular biomanufacturing.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Lab-On-A-Chip Devices , Osteogenesis , Humans , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Osteopontin/analysis , Osteopontin/metabolism , Mesenchymal Stem Cells/cytology , Immunoassay/methods , Immunoassay/instrumentation
8.
Lab Chip ; 24(8): 2358-2359, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38501991

ABSTRACT

Correction for 'Integrated biosensors for monitoring microphysiological systems' by Lei Mou et al., Lab Chip, 2022, 22, 3801-3816, https://doi.org/10.1039/D2LC00262K.

9.
iScience ; 27(3): 109277, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38455971

ABSTRACT

Tissue-resident memory T cells (TRM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of TRM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between TRM and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of TRM infiltration. TRM infiltration is associated with longer overall survival and abundance of T cells, NK cells, M1 macrophages, and memory B cells in the TIME. A 22-gene TRM-derived risk score was further developed to effectively classify patients into low- and high-risk categories, distinguishing overall survival and immune activation, particularly in T cell-mediated responses. Altogether, our analysis suggests that TRM abundance is associated with melanoma TIME activation and patient survival, and the TRM-based machine learning model can potentially predict prognosis in melanoma patients.

10.
Adv Healthc Mater ; 13(21): e2302331, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38359321

ABSTRACT

Patient-derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several challenges remain to be addressed to fully realize the potential of PDOs in therapeutic screening. This paper summarizes recent advancements in PDO development and the enhancement of PDO culture models. This is achieved by leveraging materials engineering and microfabrication technologies, including organs-on-a-chip and droplet microfluidics. Additionally, this work discusses the application of PDOs in therapy screening to meet diverse requirements and overcome bottlenecks in cancer treatment. Furthermore, this work introduces tools for data processing and analysis of organoids, along with their microenvironment. These tools aim to achieve enhanced readouts. Finally, this work explores the challenges and future perspectives of using PDOs in drug development and personalized screening for cancer patients.


Subject(s)
Neoplasms , Organoids , Humans , Organoids/drug effects , Organoids/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Precision Medicine/methods , Lab-On-A-Chip Devices , Drug Screening Assays, Antitumor/methods
11.
J Control Release ; 365: 744-758, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38072085

ABSTRACT

Amphotericin B (AmB) is the gold standard for antifungal drugs. However, AmB systemic administration is restricted because of its side effects. Here, we report AmB loaded in natural rubber latex (NRL), a sustained delivery system with low toxicity, which stimulates angiogenesis, cell adhesion and accelerates wound healing. Physicochemical characterizations showed that AmB did not bind chemically to the polymeric matrix. Electronic and topographical images showed small crystalline aggregates from AmB crystals on the polymer surface. About 56.6% of AmB was released by the NRL in 120 h. However, 33.6% of this antifungal was delivered in the first 24 h due to the presence of AmB on the polymer surface. The biomaterial's excellent hemo- and cytocompatibility with erythrocytes and human dermal fibroblasts (HDF) confirmed its safety for dermal wound application. Antifungal assay against Candida albicans showed that AmB-NRL presented a dose-dependent behavior with an inhibition halo of 30.0 ± 1.0 mm. Galleria mellonella was employed as an in vivo model for C. albicans infection. Survival rates of 60% were observed following the injection of AmB (0.5 mg.mL-1) in G. mellonella larvae infected by C. albicans. Likewise, AmB-NRL (0.5 mg.mL-1) presented survival rates of 40%, inferring antifungal activity against fungus. Thus, NRL adequately acts as an AmB-sustained release matrix, which is an exciting approach, since this antifungal is toxic at high concentrations. Our findings suggest that AmB-NRL is an efficient, safe, and reasonably priced ($0.15) dressing for the treatment of cutaneous fungal infections.


Subject(s)
Candidiasis , Wound Infection , Humans , Amphotericin B , Antifungal Agents/chemistry , Bandages , Candida albicans , Candidiasis/drug therapy , Latex , Microbial Sensitivity Tests , Wound Infection/drug therapy
12.
Acta Biomater ; 172: 67-91, 2023 12.
Article in English | MEDLINE | ID: mdl-37806376

ABSTRACT

The field of cancer immunotherapy has shown significant growth, and researchers are now focusing on effective strategies to enhance and prolong local immunomodulation. Injectable hydrogels (IHs) have emerged as versatile platforms for encapsulating and controlling the release of small molecules and cells, drawing significant attention for their potential to enhance antitumor immune responses while inhibiting metastasis and recurrence. IHs delivering natural killer (NK) cells, T cells, and antigen-presenting cells (APCs) offer a viable method for treating cancer. Indeed, it can bypass the extracellular matrix and gradually release small molecules or cells into the tumor microenvironment, thereby boosting immune responses against cancer cells. This review provides an overview of the recent advancements in cancer immunotherapy using IHs for delivering NK cells, T cells, APCs, chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. First, we introduce IHs as a delivery matrix, then summarize their applications for the local delivery of small molecules and immune cells to elicit robust anticancer immune responses. Additionally, we discuss recent progress in IHs systems used for local combination therapy, including chemoimmunotherapy, radio-immunotherapy, photothermal-immunotherapy, photodynamic-immunotherapy, and gene-immunotherapy. By comprehensively examining the utilization of IHs in cancer immunotherapy, this review aims to highlight the potential of IHs as effective carriers for immunotherapy delivery, facilitating the development of innovative strategies for cancer treatment. In addition, we demonstrate that using hydrogel-based platforms for the targeted delivery of immune cells, such as NK cells, T cells, and dendritic cells (DCs), has remarkable potential in cancer therapy. These innovative approaches have yielded substantial reductions in tumor growth, showcasing the ability of hydrogels to enhance the efficacy of immune-based treatments. STATEMENT OF SIGNIFICANCE: As cancer immunotherapy continues to expand, the mode of therapeutic agent delivery becomes increasingly critical. This review spotlights the forward-looking progress of IHs, emphasizing their potential to revolutionize localized immunotherapy delivery. By efficiently encapsulating and controlling the release of essential immune components such as T cells, NK cells, APCs, and various therapeutic agents, IHs offer a pioneering pathway to amplify immune reactions, moderate metastasis, and reduce recurrence. Their adaptability further shines when considering their role in emerging combination therapies, including chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. Understanding IHs' significance in cancer therapy is essential, suggesting a shift in cancer treatment dynamics and heralding a novel period of focused, enduring, and powerful therapeutic strategies.


Subject(s)
Hydrogels , Neoplasms , Humans , Hydrogels/therapeutic use , Immunotherapy/methods , Neoplasms/pathology , T-Lymphocytes , Combined Modality Therapy , Tumor Microenvironment
13.
Biomed Microdevices ; 25(4): 37, 2023 09 23.
Article in English | MEDLINE | ID: mdl-37740819

ABSTRACT

Trans-endothelial electrical resistance (TEER) is one of the most widely used indicators to quantify the barrier integrity of endothelial layers. Over the last decade, the integration of TEER sensors into organ-on-a-chip (OOC) platforms has gained increasing interest for its efficient and effective measurement of TEER in OOCs. To date, microfabricated electrodes or direct insertion of wires has been used to integrate TEER sensors into OOCs, with each method having advantages and disadvantages. In this study, we developed a TEER-SPE chip consisting of carbon-based screen-printed electrodes (SPEs) embedded in a poly(methyl methacrylate) (PMMA)-based multi-layered microfluidic device with a porous poly(ethylene terephthalate) membrane in-between. As proof of concept, we demonstrated the successful cultures of hCMEC/D3 cells and the formation of confluent monolayers in the TEER-SPE chip and obtained TEER measurements for 4 days. Additionally, the TEER-SPE chip could detect changes in the barrier integrity due to shear stress or an inflammatory cytokine (i.e., tumor necrosis factor-α). The novel approach enables a low-cost and facile fabrication of carbon-based SPEs on PMMA substrates and the subsequent assembly of PMMA layers for rapid prototyping. Being cost-effective and cleanroom-free, our method lowers the existing logistical and technical barriers presenting itself as another step forward to the broader adoption of OOCs with TEER measurement capability.


Subject(s)
Microphysiological Systems , Polymethyl Methacrylate , Electric Impedance , Carbon , Electrodes
14.
Int J Biol Macromol ; 249: 126016, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37516224

ABSTRACT

Films and coatings manufactured with bio-based renewable materials, such as biopolymers and essential oils, could be a sustainable and eco-friendly alternative for protecting and preserving agricultural products. In this work, we developed films and coatings from pectin and chitosan to protect strawberries (Fragaria x ananassa Duch.) from spoilage and microbial contamination. We developed three coatings containing equal amounts of glycerol and Sicilian lemon essential oil (LEO) nanoemulsion. We identified seventeen chemicals from LEO by GC-MS chromatogram, including d-limonene, α-Pinene, ß-Pinene, and γ-Terpinene. The pectin and chitosan coatings were further characterized using different physicochemical, mechanical, and biological methods. The films demonstrated satisfactory results in strength and elongation at the perforation as fruit packaging. In addition, the coatings did not influence the weight and firmness of the strawberry pulps. We observed that 100 % essential oil was released in 1440 min resulting from the erosion process. Also, the oil preserved the chemical stability of the films. Antioxidant activity (AA), measured by Electron Paramagnetic Resonance (EPR), showed that the coatings loaded with 2 % LEO nanoemulsion (PC + oil) showed that almost 50 % of AA from LEO nanoemulsion was preserved. The chitosan and the pectin-chitosan coatings (PC + oil) inhibited filamentous fungi and yeast contaminations in strawberries for at least 14 days, showing a relationship between the AA and antimicrobial results.


Subject(s)
Chitosan , Fragaria , Oils, Volatile , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Fragaria/microbiology , Chitosan/chemistry , Pectins/pharmacology , Pectins/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Food Preservation/methods
15.
Biofabrication ; 15(3)2023 06 02.
Article in English | MEDLINE | ID: mdl-37216933

ABSTRACT

Soft tissue defects are a common clinical challenge mostly caused by trauma, congenital anomalies and oncological surgery. Current soft tissue reconstruction options include synthetic materials (fillers and implants) and autologous adipose tissue transplantation through flap surgery and/or lipotransfer. Both reconstructive options hold important disadvantages to which vascularized adipose tissue engineering (VATE) strategies could offer solutions. In this review, we first summarized pivotal characteristics of functional adipose tissue such as the structure, function, cell types, development and extracellular matrix (ECM). Next, we discussed relevant cell sources and how they are applied in different state-of-the-art VATE techniques. Herein, biomaterial scaffolds and hydrogels, ECMs, spheroids, organoids, cell sheets, three dimensional printing and microfluidics are overviewed. Also, we included extracellular vesicles and emphasized their potential role in VATE. Lastly, current challenges and future perspectives in VATE are pointed out to help to pave the road towards clinical applications.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Tissue Scaffolds/chemistry , Tissue Engineering/methods , Adipose Tissue , Biocompatible Materials , Hydrogels
16.
Micromachines (Basel) ; 14(5)2023 Apr 29.
Article in English | MEDLINE | ID: mdl-37241602

ABSTRACT

Engineered human tissues created by three-dimensional cell culture of human cells in a hydrogel are becoming emerging model systems for cancer drug discovery and regenerative medicine. Complex functional engineered tissues can also assist in the regeneration, repair, or replacement of human tissues. However, one of the main hurdles for tissue engineering, three-dimensional cell culture, and regenerative medicine is the capability of delivering nutrients and oxygen to cells through the vasculatures. Several studies have investigated different strategies to create a functional vascular system in engineered tissues and organ-on-a-chips. Engineered vasculatures have been used for the studies of angiogenesis, vasculogenesis, as well as drug and cell transports across the endothelium. Moreover, vascular engineering allows the creation of large functional vascular conduits for regenerative medicine purposes. However, there are still many challenges in the creation of vascularized tissue constructs and their biological applications. This review will summarize the latest efforts to create vasculatures and vascularized tissues for cancer research and regenerative medicine.

17.
Adv Sci (Weinh) ; 10(23): e2204681, 2023 08.
Article in English | MEDLINE | ID: mdl-37217831

ABSTRACT

Aerogel-based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol-gel, aging, drying, and self-assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic-based technologies and 3D printing can be combined with aerogel-based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel-based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels.


Subject(s)
Biocompatible Materials , Tissue Engineering , Desiccation/methods , Wound Healing
18.
Adv Healthc Mater ; 12(27): e2301096, 2023 10.
Article in English | MEDLINE | ID: mdl-37256647

ABSTRACT

Peptide-based hydrogel biomaterials have emerged as an excellent strategy for immune system modulation. Peptide-based hydrogels are supramolecular materials that self-assemble into various nanostructures through various interactive forces (i.e., hydrogen bonding and hydrophobic interactions) and respond to microenvironmental stimuli (i.e., pH, temperature). While they have been reported in numerous biomedical applications, they have recently been deemed promising candidates to improve the efficacy of cancer immunotherapies and treatments. Immunotherapies seek to harness the body's immune system to preemptively protect against and treat various diseases, such as cancer. However, their low efficacy rates result in limited patient responses to treatment. Here, the immunomaterial's potential to improve these efficacy rates by either functioning as immune stimulators through direct immune system interactions and/or delivering a range of immune agents is highlighted. The chemical and physical properties of these peptide-based materials that lead to immuno modulation and how one may design a system to achieve desired immune responses in a controllable manner are discussed. Works in the literature that reports peptide hydrogels as adjuvant systems and for the delivery of immunotherapies are highlighted. Finally, the future trends and possible developments based on peptide hydrogels for cancer immunotherapy applications are discussed.


Subject(s)
Nanostructures , Neoplasms , Humans , Hydrogels/chemistry , Immunotherapy , Peptides/chemistry , Nanostructures/chemistry , Neoplasms/therapy
19.
Int J Biol Macromol ; 242(Pt 1): 124779, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37172697

ABSTRACT

Psoriasis is a disease that causes keratinocytes to proliferate ten times faster than normal, resulting in chronic inflammation and immune cell infiltration in the skin. Aloe vera (A. vera) creams have been used topically for treating psoriasis because they contain several antioxidant species; however, they have several limitations. Natural rubber latex (NRL) has been used as occlusive dressings to promote wound healing by stimulating cell proliferation, neoangiogenesis, and extracellular matrix formation. In this work, we developed a new A. vera-releasing NRL dressing by a solvent casting method to load A. vera into NRL. FTIR and rheological analyzes revealed no covalent interactions between A. vera and NRL in the dressing. We observed that 58.8 % of the loaded A. vera, present on the surface and inside the dressing, was released after 4 days. Biocompatibility and hemocompatibility were validated in vitro using human dermal fibroblasts and sheep blood, respectively. We observed that ~70 % of the free antioxidant properties of A. vera were preserved, and the total phenolic content was 2.31-fold higher than NRL alone. In summary, we combined the antipsoriatic properties of A. vera with the healing activity of NRL to generate a novel occlusive dressing that may be indicated for the management and/or treatment of psoriasis symptoms simply and economically.


Subject(s)
Aloe , Psoriasis , Humans , Animals , Sheep , Rubber , Latex , Antioxidants/pharmacology , Psoriasis/drug therapy , Bandages
20.
Int J Biol Macromol ; 242(Pt 1): 124778, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37172704

ABSTRACT

Natural rubber latex (NRL) is a biopolymer widely used in biomedical applications. In this work, we propose an innovative cosmetic face mask, combining the NRL's biological properties with curcumin (CURC), which has a high level of antioxidant activity (AA) to provide anti-aging benefits. Chemical, mechanical and morphological characterizations were performed. The CURC released by the NRL was evaluated by permeation in Franz cells. Cytotoxicity and hemolytic activity assays were performed to assess safety. The findings showed that the biological properties of CURC were preserved after loading in the NRL. About 44.2 % of CURC was released within the first six hours, and in vitro permeation showed that 9.36 % ± 0.65 was permeated over 24h. CURC-NRL was associated with a metabolic activity higher than 70 % in 3 T3 fibroblasts, cell viability ≥95 % in human dermal fibroblasts, and a hemolytic rate ≤ 2.24 % after 24 h. Furthermore, CURC-NRL maintained the mechanical characteristics (range suitable) for human skin application. We observed that CURC-NRL preserved ~20 % antioxidant activity from curcumin-free after loading in the NRL. Our results suggest that CURC-NRL has the potential to be used in the cosmetics industry, and the experimental methodology utilized in this study can be applied to different kinds of face masks.


Subject(s)
Curcumin , Rubber , Humans , Antioxidants/pharmacology , Masks , Curcumin/pharmacology , Curcumin/chemistry , Aging
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