Rosanne M. Raftery's research while affiliated with Trinity College Dublin and other places

Publications (26)

Article
Full-text available
Gene activated scaffolds incorporating star-shaped polypeptide-pDNA nanomedicines accelerate bone tissue regeneration in vivo .
Article
Leveraging the differential response of genes to mechanical loading may allow for the identification of novel therapeutics and we have recently established placental growth factor (PGF) as a mechanically augmented gene which promotes angiogenesis at higher doses and osteogenesis at lower doses. Herein, we sought to execute a mechanobiology-informed...
Article
Full-text available
Correction for ‘ In vitro vascularization of tissue engineered constructs by non-viral delivery of pro-angiogenic genes’ by Helena R. Moreira et al. , Biomater. Sci. , 2021, DOI: 10.1039/d0bm01560a.
Article
Vascularization is still one of the major challenges in tissue engineering. In the context of tissue regeneration, the formation of capillary-like structures is often triggered by the addition of growth...
Article
We have recently demonstrated that c-Jun N-terminal kinase 3 (JNK3) is a key modulator of the enhanced osteogenic potential of stem cells derived from children when compared to those derived from adults. In this study, we formulated a JNK3-activator nanoparticle (JNK3*) that recapitulates the immense osteogenic potential of juvenile cells in adult...
Chapter
microRNAs are small and evolutionary conserved RNA molecules that vastly fine-tune protein expression at a posttranscriptional level. microRNA modulation has recently surfaced as powerhouse feeding the progress of novel strategies for tissue and cell engineering and regeneration. The field is growing exponentially each year and approaching clinical...
Article
Current treatments for articular cartilage defects relieve symptoms but often only delay cartilage degeneration. Mesenchymal stem cells (MSCs) have shown chondrogenic potential but tend to undergo endochondral ossification when implanted in vivo. Harnessing factors governing joint development to functionalize biomaterial scaffolds, termed developme...
Article
microRNAs offer vast therapeutic potential for multiple disciplines. From a bone perspective, inhibition of miR-133a may offer potential to enhance Runx2 activity and increase bone repair. This study aims to assess the therapeutic capability of antagomiR-133a delivery from collagen-nanohydroxyapatite (coll-nHA) scaffolds following cell-free implant...
Article
The healing of large, critically sized, bone defects remains an unmet clinical need in modern orthopaedic medicine. The tissue engineering field is increasingly using biomaterial scaffolds as 3D templates to guide the regenerative process which can be further augmented via the incorporation of recombinant growth factors. Typically, this necessitate...
Article
It is increasingly being recognised within the field of tissue engineering that the regenerative capacity of biomaterial scaffolds can be augmented via the incorporation of gene therapeutics. However, the field still lacks a biocompatible gene delivery vector which is capable of functionalizing scaffolds for tailored nucleic acid delivery. Herein,...
Article
Recent advances in tissue engineering have made progress towards the development of biomaterials capable of the delivery of growth factors, such as BMPs, in order to promote enhanced tissue repair. However, controlling the release of these growth factors on demand and within the desired localised area is a significant challenge and the associated h...
Article
Full-text available
Statement of significance: The basic requirements of biomaterial-based nerve guidance conduits have now been well established and include being able to bridge a nerve injury to support macroscopic guidance between nerve stumps, while being strong enough to withstand longitudinal tension and circumferential compression, in addition to being mechani...
Article
Gene-activated scaffolds have been shown to induce controlled, sustained release of functional transgene both in vitro and in vivo. Bone morphogenetic proteins (BMPs) are potent mediators of osteogenesis however we found that the delivery of plasmid BMP-2 (pBMP-2) alone was not sufficient to enhance bone formation. Therefore, the aim of this study...
Article
Dimensionality can have a profound impact on stiffness-mediated differentiation of mesenchymal stem cells (MSCs). However, while we have begun to understand cellular response when encapsulated within 3D substrates, the behavior of cells within macro-porous substrates is relatively underexplored. The goal of this study was to determine the influence...
Article
The field of tissue engineering is increasingly recognizing that gene therapy can be employed for modulating in vivo cellular response thereby guiding tissue regeneration. However, the field lacks a versatile and biocompatible gene delivery platform capable of efficiently delivering transgenes to mesenchymal stem cells (MSCs), a cell type refractor...
Article
Ensuring an adequate angiogenic response during wound healing is a prevailing clinical challenge in biomaterials science. To address this, we aimed to develop a pro-angiogenic gene-activated scaffold (GAS) that could activate MSCs to produce paracrine factors and influence angiogenesis and wound repair. A non-viral polyethyleneimine (PEI) nanoparti...
Article
siRNA has emerged as a potential therapeutic for the treatment of prostate cancer but effective delivery remains a major barrier to its clinical application. This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-media...
Article
Unlabelled: Natural biomaterials such as collagen show promise in tissue engineering applications due to their inherent bioactivity. The main limitation of collagen is its low mechanical strength and somewhat unpredictable and rapid degradation rate; however, combining collagen with another material, such as chitosan, can reinforce the scaffold me...
Article
As well as acting to fill defects and allow for cell infiltration and proliferation in regenerative medicine, biomaterial scaffolds can also act as carriers for therapeutics, further enhancing their efficacy. Drug and protein delivery on scaffolds have shown potential, however, supraphysiological quantities of therapeutic are often released at the...
Article
Biomaterial scaffolds that support cell infiltration and tissue formation can also function as platforms for the delivery of therapeutics such as drugs, proteins and genes. As burst release of supraphysiological quantities of recombinant proteins can result in adverse side effects, the objective of this study was to explore the potential of a serie...
Article
Gene therapy involves the introduction of foreign genetic material into cells in order exert a therapeutic effect. The application of gene therapy to the field of orthopaedic tissue engineering is extremely promising as the controlled release of therapeutic proteins such as bone morphogenetic proteins have been shown to stimulate bone repair. Howev...

Citations

... This study illustrated that a novel class of biomaterials in the star-polypeptides form could successfully deliver a cargo of therapeutic pDNA from a collagen-based scaffold in vivo with the ability to reconstruct bone tissue as a result of this delivery. The in vitro results exhibited that the co-delivery of VEGF and BMP-2 by the 64-star-polypeptides vector can be applied to stimulate MSC-mediated osteogenesis on various collagen-based scaffolds with a diversity of macromolecular compositions [97]. ...
... Song et al. reported that supplementing fibroblast factor 2 reversed catabolism to anabolic metabolism under cartilage damage, which was helpful to stabilize the ECM and promote cartilage regeneration [108]. Supported and delivered by a sodium alginate particle-COL/hydroxyapatite composite scaffold, placental growth factor exhibited cartilage repair ability with a low-dose release [109]. However, due to the short half-lives, high cost, intolerance to sterilization conditions, sensitivity to pH, proneness to proteolysis, and rapid elimination in vivo [110], the long-term and stable release of growth factors relying on pore diffusion is hard to achieve by simply adding them into collagenbased biomaterials. ...
... In the study of Moreira (Moreira et al., 2021), plasmid vectors were attached to IMBs for the continuous production of repairand regeneration-related proteins (e.g., VEGF and FGF) to promote tissue regeneration and repair. In this study, based on the original porous sponge material, chitosan (Ch) and polyethyleneimine (PEI) were used as nonviral vectors to transfer the plasmid encoding vascular endothelial growth factor (p-VEGF) and the plasmid encoding fibroblast growth factor-2 (p-FGF-2). ...
... Following this, the porous scaffolds were dehydrothermally (DHT) crosslinked in a vacuum oven (VacuCell, MMM, Planegg, Germany) for 24 h at a pressure of 0.05 bar and a temperature of 105 • C. To obtain a sufficient quantity of human bone-marrow MSCs, cells were first expanded in monolayer prior to seeding on the scaffolds. MSCs were either purchased from Lonza (Basel, Switzerland) or isolated from the iliac crest of adults (donor age range: 20-30 years old) using standardised protocols and including a stringent analysis of cell phenotype as previously described [31]. Cells were incubated with low-glucose Dulbecco's modified Eagle's medium (DMEM) (Sigma-Aldrich, Arklow, Ireland) supplemented with 10% fetal bovine serum (ThermoFisher Scientific, Dublin, Ireland) and 1% penicillin/streptomycin (ThermoFisher Scientific, Dublin, Ireland). ...
... MSCs isolated from bone marrow or fat show good differentiation ability and are commonly applied to repair osteochondral injury; they are confirmed as ideal cell resources for cartilage regeneration owing to their easy acquisition from adult tissues and frequent expansion in vitro [118]. Nevertheless, depending on the age of the donor and the passage number, MSCs exhibit differentiation instability in vivo, and endochondral ossification may also occur [7,119]. Progenitor cells from articular cartilage have been proven to be a potential substitute for BMSCs. ...
... However, there is relatively little research on its role in regulating the function of macrophages in bone regeneration. Castaño et al. (2020) designed a collagen nano-hydroxyapatite scaffold that could deliver the antagomiR-133a. With the local release of antagomiR-133a, the number of M2 phenotype macrophages was significantly elevated, resulting in a considerable increase in bone volume in the animal bone defect model. ...
... Third, without protection from wound dressings or adhesives, mTG may be washed out rapidly in mucosal wounds to attenuate the influence of ADSCs. Furthermore, the osseous defect fill in this study was obviously lower than that in other relevant animal studies [32][33][34], and the potential reason was the lack of the osteoconductive framework provided by the scaffold. The combination of ADsp with osteoconductive scaffolds, such as 3D-printed hydroxyapatite-based scaffolds [35], may be beneficial to promote the efficiency of ADsp-mTG for osseous defect regeneration. ...
... (B) A gene delivery system has been designed by researchers containing a GET-pDNA (a novel multidomain containing both a cell-binding sequence and cell-penetrating peptide) that enhances cell interaction and intracellular translocation of nucleic acids. This system can be inserted into the scaffold used in a cell-free model in vitro [86]. (C) Application of synthetic biology in TE and scaffolds. ...
... GET-pBMP-2activated scaffolds allowed for cell infiltration through the 3D matrix, controlled release of the gene into cells, and efficient gene expression, improving osteogenesis and repair of critical-sized bone defects in vivo. Also, they described similar collagen-based and gene-activated scaffold platforms with star-shaped poly-lysine polypeptides (star-PLLs) incorporated [234]. The star-PLL-pDNA nanomedicine scaffold facilitated increased and prolonged transgene expression with spatiotemporal control in MSCs compared to the linear-PLL vector and enabled autologous host cell infiltration in an in vivo subcutaneous implant model. ...
... However, clinical gene therapy is still hindered by different physiological barriers in the recipient, including physical obstacles (body fluids, dense joint extracellular matrices) and biological inhibitors (pH/enzymatic environment of the joint, neutralizing host immune responses, rate-limiting intracellular steps, gene dissemination to non-target locations) [83,[94][95][96][97][98]. A very innovative approach to tackle these problems is to provide therapeutic gene vectors via biomaterial-guided delivery in sites of ACL injury as an offthe-shelf system, allowing for a safe, stabilized, and protected controlled release of the gene vehicles using biocompatible scaffolds (cargos) [82,83,87,90,[99][100][101][102][103][104]. The goal of this work is, therefore, to provide an overview of the most advanced gene therapy procedures that aim at enhancing the repair of ACL injuries. ...