Publications
23 results found
Loecher A, Bruyns-Haylett M, Ballester PJ, et al., 2023, A machine learning approach to predict cellular uptake of pBAE polyplexes, BIOMATERIALS SCIENCE, Vol: 11, Pages: 5797-5808, ISSN: 2047-4830
Anna DY R, Duran-Mota JA, Oliva Jorge N, 2022, Current progress in bionanomaterials to modulate the epigenome, Biomaterials Science, Vol: 10, Pages: 5081-5091, ISSN: 2047-4830
Recent advances in genomics during the 1990s have made it possible to study and identify genetic and epigenetic responses of cells and tissues to various drugs and environmental factors. This has accelerated the number of targets available to treat a range of diseases from cancer to wound healing disorders. Equally interesting is the understanding of how bio- and nano-materials alter gene expression through epigenetic mechanisms, and whether they have the potential to elicit a positive therapeutic response without requiring additional biomolecule delivery. In fact, from a cell’s perspective, a biomaterial is nothing more than an environmental factor, and so it has the power to epigenetically modulate gene expression of cells in contact with it. Understanding these epigenetic interactions between biomaterials and cells will open new avenues in the development of technologies that can not only provide biological signals (i.e. drugs, growth factors) necessary for therapy and regeneration, but also intimately interact with cells to promote the expression of genes of interest. This review article aims to summarise the current state-of-the-art and progress on the development of bio- and nanomaterials to modulate the epigenome.
Oliva N, Shin M, Burdick JA, 2021, Editorial: special issue on advanced biomedical hydrogels., ACS Biomaterials Science and Engineering, Vol: 7, Pages: 3993-3996, ISSN: 2373-9878
Duran Mota JA, Quintanas Yani J, Almquist B, et al., 2021, Polyplex-loaded hydrogels for local gene delivery to human dermal fibroblasts, ACS Biomaterials Science and Engineering, Vol: 7, Pages: 4347-4361, ISSN: 2373-9878
Impaired cutaneous healing leading to chronic wounds affects between 2 and 6% of the total population in most developed countries and it places a substantial burden on healthcare budgets. Current treatments involving antibiotic dressings and mechanical debridement are often not effective, causing severe pain, emotional distress, and social isolation in patients for years or even decades, ultimately resulting in limb amputation. Alternatively, gene therapy (such as mRNA therapies) has emerged as a viable option to promote wound healing through modulation of gene expression. However, protecting the genetic cargo from degradation and efficient transfection into primary cells remain significant challenges in the push to clinical translation. Another limiting aspect of current therapies is the lack of sustained release of drugs to match the therapeutic window. Herein, we have developed an injectable, biodegradable and cytocompatible hydrogel-based wound dressing that delivers poly(β-amino ester)s (pBAEs) nanoparticles in a sustained manner over a range of therapeutic windows. We also demonstrate that pBAE nanoparticles, successfully used in previous in vivo studies, protect the mRNA load and efficiently transfect human dermal fibroblasts upon sustained release from the hydrogel wound dressing. This prototype wound dressing technology can enable the development of novel gene therapies for the treatment of chronic wounds.
Duran-Mota JA, Quintanas Yani J, Almquist B, et al., 2021, Polyplex-Loaded Hydrogels for Local Gene Delivery to Human Dermal Fibroblasts
<jats:p>Impaired cutaneous healing, leading to chronic wounds, affects between 2 and 6% of the total population in most developed countries and it places a substantial burden on healthcare budgets. Current treatments involving antibiotic dressings and mechanical debridement are often not effective, causing severe pain, emotional distress and social isolation in patients for years or even decades, ultimately resulting in limb amputation. Alternatively, gene therapy (such as mRNA therapies) emerges as a viable option to promote wound healing through modulation of gene expression. However, protecting the genetic cargo from degradation and efficient transfection into primary cells remain significant challenges in the push to clinical translation. Another limiting aspect of current therapies is the lack of sustained release of drugs to match the therapeutic window. Herein, we have developed an injectable, biodegradable and biocompatible hydrogel-based wound dressing that delivers pBAE nanoparticles in a sustained manner over a range of therapeutic windows. We also demonstrate that pBAE nanoparticles, successfully used in previous <jats:italic>in vivo</jats:italic> studies, protect the mRNA load and efficiently transfect human dermal fibroblasts upon sustained release from the hydrogel wound dressing. This prototype wound dressing technology can enable the development of novel gene therapies for the treatment of chronic wounds.</jats:p>
Duran-Mota JA, Oliva N, Almquist BD, 2021, Chapter 19: Nanobiomaterials for Smart Delivery, RSC Soft Matter, Pages: 475-498
The human body is a complex system where several interconnected dynamic processes work in an orchestrated manner to carry out the many different body functions. However, pathological conditions may cause dysregulations of these body functions. Biomedicine aims to understand such dysregulations and restore normal, healthy function within bodies. A wide variety of therapeutics have been used since ancient times, but their traditional systemic administration lacks spatiotemporal control over the delivery. Recent progress in chemistry and physics, along with the emergence of nanotechnology, has allowed the development of new strategies to solve this drawback such as stimuli-responsive nanobiomaterials. This new class of materials can be designed to respond to chemical and physical stimuli associated with pathological dysregulations (for example, changes in pH or redox environment, or the increase of certain biomolecules in the bloodstream). Alternatively, stimuli can also be provided externally (such as magnetic fields or light) to trigger the controlled release of therapeutics. Hydrogels are one of the most promising materials to achieve complete spatiotemporal control as they are typically injected or implanted where they are needed. Moreover, the chemical structure of the polymers forming the hydrogel can be easily manipulated to make them stimuli-responsive. This chapter focuses on the chemical and physical mechanisms that confer stimuli-responsive properties to polymers, enabling the development of smart hydrogels for spatiotemporal delivery of drugs.
Oliva Jorge N, Almquist B, 2020, Spatiotemporal delivery of bioactive molecules for wound healing using stimuli-responsive biomaterials, Advanced Drug Delivery Reviews, Vol: 161-162, Pages: 22-41, ISSN: 0169-409X
Wound repair is a fascinatingly complex process, with overlapping events in both space and time needed to pave a pathway to successful healing. This additional complexity presents challenges when developing methods for the controlled delivery of therapeutics for wound repair and tissue engineering. Unlike more traditional applications, where biomaterial-based depots increase drug solubility and stability in vivo, enhance circulation times, and improve retention in the target tissue, when aiming to modulate wound healing, there is a desire to enable localised, spatiotemporal control of multiple therapeutics. Furthermore, many therapeutics of interest in the context of wound repair are sensitive biologics (e.g. growth factors), which present unique challenges when designing biomaterial-based delivery systems. Here, we review the diverse approaches taken by the biomaterials community for creating stimuli-responsive materials that are beginning to enable spatiotemporal control over the delivery of therapeutics for applications in tissue engineering and regenerative medicine.
Oliva-Jorge N, Almquist B, 2020, Bioinspired nanomaterials for cell-selective activation of growth factors to promote healing, Publisher: WILEY, Pages: S6-S7, ISSN: 1067-1927
Zhang Y, Dosta P, Conde J, et al., 2020, Prolonged Local In Vivo Delivery of Stimuli-Responsive Nanogels That Rapidly Release Doxorubicin in Triple-Negative Breast Cancer Cells, ADVANCED HEALTHCARE MATERIALS, Vol: 9, ISSN: 2192-2640
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- Citations: 39
Stejskalova A, Oliva Jorge N, England F, et al., 2019, Biologically inspired, cell-selective release of aptamer-trapped growth factors by traction forces, Advanced Materials, Vol: 31, Pages: 1-8, ISSN: 0935-9648
Biomaterial scaffolds that are designed to incorporate dynamic, spatiotemporal information have the potential to interface with cells and tissues to direct behavior. Here we describe a bioinspired, programmable nanotechnology-based platform that harnesses cellular traction forces to activate growth factors, eliminating the need for exogenous triggers (e.g. light), spatially diffuse triggers (e.g. enzymes, pH changes) or passive activation (e.g. hydrolysis). We use flexible aptamer technology to create modular, synthetic mimics of the Large Latent Complex that restrains TGF-β1. This flexible nanotechnology-based approach is shown here to work with both platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF-165), integrate with glass coverslips, polyacrylamide gels, and collagen scaffolds, enable activation by various cells (e.g. primary human dermal fibroblasts, HMEC-1 endothelial cells) and unlock fundamentally new capabilities such as selective activation of growth factors by differing cell types (e.g. activation by smooth muscle cells but not fibroblasts) within clinically relevant collagen sponges.
Oliva N, Conde J, Wang K, et al., 2017, Designing Hydrogels for On-Demand Therapy, ACCOUNTS OF CHEMICAL RESEARCH, Vol: 50, Pages: 669-679, ISSN: 0001-4842
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- Citations: 187
Conde J, Oliva N, Zhang Y, et al., 2016, Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model, NATURE MATERIALS, Vol: 15, Pages: 1128-+, ISSN: 1476-1122
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- Citations: 346
Gilam A, Conde J, Weissglas-Volkov D, et al., 2016, Local microRNA delivery targets Palladin and prevents metastatic breast cancer, NATURE COMMUNICATIONS, Vol: 7
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- Citations: 107
Conde J, Oliva N, Artzi N, 2016, Revisiting the 'One Material Fits All' Rule for Cancer Nanotherapy, TRENDS IN BIOTECHNOLOGY, Vol: 34, Pages: 618-626, ISSN: 0167-7799
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- Citations: 6
Conde J, Oliva N, Atilano M, et al., 2016, Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment, NATURE MATERIALS, Vol: 15, Pages: 353-+, ISSN: 1476-1122
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- Citations: 196
Oliva N, Artzi N, 2015, Injectable hydrogels as tissue adhesives, Injectable Hydrogels For Regenerative Engineering, Pages: 239-273, ISBN: 9781783267477
The following sections are included: Introduction Adhesives Tissue Adhesives for Medical Applications Current View on Adhesive Hydrogels Tissue Adhesive Characterization Techniques Using Fluorescent Probes Summary and Implications References.
Oliva N, Unterman S, Zhang Y, et al., 2015, Personalizing Biomaterials for Precision Nanomedicine Considering the Local Tissue Microenvironment, ADVANCED HEALTHCARE MATERIALS, Vol: 4, Pages: 1584-1599, ISSN: 2192-2640
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- Citations: 40
Conde J, Oliva N, Artzi N, 2015, Implantable hydrogel embedded dark-gold nanoswitch as a theranostic probe to sense and overcome cancer multidrug resistance, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 112, Pages: E1278-E1287, ISSN: 0027-8424
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- Citations: 101
Oliva N, Carcole M, Beckerman M, et al., 2015, Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia, SCIENCE TRANSLATIONAL MEDICINE, Vol: 7, ISSN: 1946-6234
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- Citations: 55
Segovia N, Pont M, Oliva N, et al., 2015, Hydrogel Doped with Nanoparticles for Local Sustained Release of siRNA in Breast Cancer, ADVANCED HEALTHCARE MATERIALS, Vol: 4, Pages: 271-280, ISSN: 2192-2640
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- Citations: 95
Oliva N, Shitreet S, Abraham E, et al., 2012, Natural Tissue Microenvironmental Conditions Modulate Adhesive Material Performance, LANGMUIR, Vol: 28, Pages: 15402-15409, ISSN: 0743-7463
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- Citations: 30
Artzi N, Oliva N, Puron C, et al., 2011, <i>In vivo</i> and <i>in vitro</i> tracking of erosion in biodegradable materials using non-invasive fluorescence imaging (vol 10, pg 704, 2011), NATURE MATERIALS, Vol: 10, Pages: 896-896, ISSN: 1476-1122
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- Citations: 4
Artzi N, Oliva N, Puron C, et al., 2011, In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging, Nature Materials, Vol: 10, Pages: 704-709, ISSN: 1476-1122
The design of erodible biomaterials relies on the ability to program the in vivo retention time, which necessitates real-time monitoring of erosion. However, in vivo performance cannot always be predicted by traditional determination of in vitro erosion1,2, and standard methods sacrifice samples or animals3, preventing sequential measures of the same specimen. We harnessed non-invasive fluorescence imaging to sequentially follow in vivo material-mass loss to model the degradation of materials hydrolytically (PEG:dextran hydrogel) and enzymatically (collagen). Hydrogel erosion rates in vivo and in vitro correlated, enabling the prediction of in vivo erosion of new material formulations from in vitro data. Collagen in vivo erosion was used to infer physiologic in vitro conditions that mimic erosive in vivo environments. This approach enables rapid in vitro screening of materials, and can be extended to simultaneously determine drug release and material erosion from a drug-eluting scaffold, or cell viability and material fate in tissue-engineering formulations.
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