Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds

Raftery, Rosanne M.; Tierney, Erica G.; Curtin, Caroline M.; Cryan, Sally‐Ann; O’Brien, Fergal J.

doi:10.1016/j.jconrel.2015.05.005

Cited by 92 publications

(75 citation statements)

References 57 publications

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“…This GAM was used to culture periodontal ligament cells, which achieved high proliferation, formed a periodontal connective tissue‐like structure after two weeks, and maintained a fibroblast figure. In another study, Raftery et al developed and optimized chitosan–pDNA nanoparticles that facilitated MSC transfection via incorporation into collagen‐based scaffolds …”

Section: Properties Of Soft Nanoparticle–functionalized Hydrogelsmentioning

confidence: 99%

Soft‐Nanoparticle Functionalization of Natural Hydrogels for Tissue Engineering Applications

Elkhoury

Russell

Sánchez-González

et al. 2019

Adv Healthcare Materials

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Tissue engineering has emerged as an important research area that provides numerous research tools for the fabrication of biologically functional constructs that can be used in drug discovery, disease modeling, and the treatment of diseased or injured organs. From a materials point of view, scaffolds have become an important part of tissue engineering activities and are usually used to form an environment supporting cellular growth, differentiation, and maturation. Among various materials used as scaffolds, hydrogels based on natural polymers are considered one of the most suitable groups of materials for creating tissue engineering scaffolds. Natural hydrogels, however, do not always provide the physicochemical and biological characteristics and properties required for optimal cell growth. This review discusses the properties and tissue engineering applications of widely used natural hydrogels. In addition, methods of modulation of their physicochemical and biological properties using soft nanoparticles as fillers or reinforcing agents are presented.

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Section: Properties Of Soft Nanoparticle–functionalized Hydrogelsmentioning

confidence: 99%

Soft‐Nanoparticle Functionalization of Natural Hydrogels for Tissue Engineering Applications

Elkhoury

Russell

Sánchez-González

et al. 2019

Adv Healthcare Materials

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“…More recently, a chitosan‐based vector delivering both pBMP‐2 and pVEGF (1 µg each) on a collagen‐hydroxyapatite scaffold resulted in the complete bridging of critical‐sized rat calvarial defects within 28 days without the detection of off‐target side effects. This study focused on the neovascularisation induced by pVEGF, demonstrating that it plays a critical role in bone regeneration as the delivery of both pVEGF and pBMP‐2 resulted in enhanced bone formation compared with the delivery of pBMP‐2 alone …”

Section: Gene‐activated Scaffolds For Orthopedic Tissue Engineeringmentioning

confidence: 99%

Scaffold‐Based Delivery of Nucleic Acid Therapeutics for Enhanced Bone and Cartilage Repair

Kelly

Raftery

Curtin

et al. 2019

Journal Orthopaedic Research

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Recent advances in tissue engineering have made progress toward the development of biomaterials capable of the delivery of growth factors, such as bone morphogenetic proteins, in order to promote enhanced tissue repair. However, controlling the release of these growth factors on demand and within the desired localized area is a significant challenge and the associated high costs and side effects of uncontrolled delivery have proven increasingly problematic in clinical orthopedics. Gene therapy may be a valuable tool to avoid the limitations of local delivery of growth factors. Following a series of setbacks in the 1990s, the field of gene therapy is now seeing improvements in safety and efficacy resulting in substantial clinical progress and a resurgence in confidence. Biomaterial scaffoldmediated gene therapy provides a template for cell infiltration and tissue formation while promoting transfection of cells to engineer therapeutic proteins in a sustained but ultimately transient fashion. Additionally, scaffold-mediated delivery of RNA-based therapeutics can silence specific genes associated with orthopedic pathological states. This review will provide an overview of the current state-of-theart in the field of gene-activated scaffolds and their use within orthopedic tissue engineering applications.

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“…[84] Thus, while 80% deacetylated chitosan showed low efficiencies transfecting pDNA, fully deacetylated chitosan demonstrated remarkable functionality of the eluted siRNA along a 5 d time-course in a human lung carcinoma cell line (H1299). [84] More recently, shortening the chain length has provided improved efficiencies (≈45%) in the transfection of rat mesenchymal stem cells with pDNA, [85] and similarly, highly depolymerized chitosan delivering miR-145 to human breast adenocarcinoma (MCF-7) cells achieved ≈50% target silencing. [86] Exosomes play a critical role in paracrine signaling and intercellular miRNA trafficking guided by the tissue-specific proteins found on their surface.…”

Section: Nonviral Vectorsmentioning

confidence: 99%

“…[96,124] Studies on scaffold-based gene delivery in the lab originally began with the delivery of pDNA including BMP2 [95] and combinations of BMP2 and VEGF [155] utilizing the nHA particles [94] and coll-nHA scaffolds [94,156] developed in-house specifically for bone repair. Having demonstrated the dramatically enhanced therapeutic potential of such systems not only for bone but also cartilage and nerve repair, we also progressed to investigating the utility of alternative gene delivery vectors including PEI, [85,155,157] chitosan, [40,158] Lipofectamine 2000, [75] and cyclodextrin, [75,159] different genetic cargo such as pDNA, [85,95,155,157] miRNA, [96,124] and siRNA, [75,159] and various scaffold types including collagen alone, [85,95] collagennHA, [75,95,96,124,155,159] collagen-HA [85] and collagen hyaluronic acid (coll-HyA) [85] to tailor our systems depending on the final application required. [158] Delivery of the miR-mimics and miR-inhibitors from porous collagen-nHA scaffolds yielded very promising results demonstrating silencing functionality of ≈20% and 88.4%, respectively.…”

Section: Osteogenesis and Bone Repairmentioning

confidence: 99%

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

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Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds

Cited by 92 publications

References 57 publications

Soft‐Nanoparticle Functionalization of Natural Hydrogels for Tissue Engineering Applications

Soft‐Nanoparticle Functionalization of Natural Hydrogels for Tissue Engineering Applications

Scaffold‐Based Delivery of Nucleic Acid Therapeutics for Enhanced Bone and Cartilage Repair

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

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