ORCID Profile
0000-0003-3831-8738
Current Organisation
Deakin University
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Central Nervous System | Medical Biotechnology | Biomaterials | Regenerative Medicine (incl. Stem Cells and Tissue Engineering) |
Expanding Knowledge in Engineering | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Medical and Health Sciences
Publisher: MDPI AG
Date: 25-05-2022
DOI: 10.3390/GELS8060332
Abstract: Metastatic tumours are complex ecosystems a community of multiple cell types, including cancerous cells, fibroblasts, and immune cells that exist within a supportive and specific microenvironment. The interplay of these cells, together with tissue specific chemical, structural and temporal signals within a three-dimensional (3D) habitat, direct tumour cell behavior, a subtlety that can be easily lost in 2D tissue culture. Here, we investigate a significantly improved tool, consisting of a novel matrix of functionally programmed peptide sequences, self-assembled into a scaffold to enable the growth and the migration of multicellular lung tumour spheroids, as proof-of-concept. This 3D functional model aims to mimic the biological, chemical, and contextual cues of an in vivo tumor more closely than a typically used, unstructured hydrogel, allowing spatial and temporal activity modelling. This approach shows promise as a cancer model, enhancing current understandings of how tumours progress and spread over time within their microenvironment.
Publisher: AIP Publishing
Date: 08-07-2021
DOI: 10.1063/5.0040764
Abstract: The debilitating effects of muscle damage, either through ischemic injury or volumetric muscle loss (VML), can have significant impacts on patients, and yet there are few effective treatments. This challenge arises when function is degraded due to significant amounts of skeletal muscle loss, beyond the regenerative ability of endogenous repair mechanisms. Currently available surgical interventions for VML are quite invasive and cannot typically restore function adequately. In response to this, many new bioengineering studies implicate 3D bioprinting as a viable option. Bioprinting for VML repair includes three distinct phases: printing and seeding, growth and maturation, and implantation and application. Although this 3D bioprinting technology has existed for several decades, the advent of more advanced and novel printing techniques has brought us closer to clinical applications. Recent studies have overcome previous limitations in diffusion distance with novel microchannel construct architectures and improved myotubule alignment with highly biomimetic nanostructures. These structures may also enhance angiogenic and nervous ingrowth post-implantation, though further research to improve these parameters has been limited. Inclusion of neural cells has also shown to improve myoblast maturation and development of neuromuscular junctions, bringing us one step closer to functional, implantable skeletal muscle constructs. Given the current state of skeletal muscle 3D bioprinting, the most pressing future avenues of research include furthering our understanding of the physical and biochemical mechanisms of myotube development and expanding our control over macroscopic and microscopic construct structures. Further to this, current investigation needs to be expanded from immunocompromised rodent and murine myoblast models to more clinically applicable human cell lines as we move closer to viable therapeutic implementation.
Publisher: Elsevier BV
Date: 2019
Publisher: CSIRO Publishing
Date: 2013
DOI: 10.1071/CH12557
Abstract: The early stages of the self-assembly of peptide hydrogels largely determine their final material properties. Here we discuss experimental methodologies for monitoring the self-assembly kinetics which underpin peptide hydrogel formation. The early stage assembly of an enzyme-catalysed Fmoc-trileucine based self-assembled hydrogel was examined using spectroscopic techniques (circular dichroism, CD, and solution NMR) as well as chromatographic (HPLC) and mechanical (rheology) techniques. Optimal conditions for enzyme-assisted hydrogel formation were identified and the kinetics examined. A lag time associated with the formation and accumulation of the self-assembling peptide monomer was observed and a minimum hydrogelator concentration required for gelation was identified. Subsequent formation of well defined nano- and microscale structures lead to self-supporting hydrogels at a range of substrate and enzyme concentrations. 1H NMR monitoring of the early self-assembly process revealed trends that were well in agreement with those identified using traditional methods (i.e. HPLC, CD, rheology) demonstrating 1H NMR spectroscopy can be used to non-invasively monitor the self-assembly of peptide hydrogels without damaging or perturbing the system.
Publisher: Elsevier BV
Date: 12-2023
Publisher: Wiley
Date: 07-01-2008
Publisher: American Chemical Society (ACS)
Date: 25-08-2017
Publisher: Springer Science and Business Media LLC
Date: 28-01-2023
DOI: 10.1038/S41467-023-36133-8
Abstract: Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7NR05004F
Abstract: Tissue-specific self-assembling peptide (SAP) hydrogels designed based on biologically relevant peptide sequences have great potential in regenerative medicine.
Publisher: Wiley
Date: 04-10-2018
Abstract: Immunology is the next frontier of nano/biomaterial science research, with the immune system determining the degree of tissue repair. However, the complexity of the inflammatory response represents a significant challenge that is essential to understand for the development of future therapies. Cell-instructive 3D culture environments are critical to improve our understanding of the link between the behavior and morphology of inflammatory cells and to remodel their response to injury. This study has taken two recent high-profile innovations-functional peptide-based hydrogels, and the inclusion of anti-inflammatory agents via coassembly-to make a programmed anti-inflammatory nanoscaffold (PAIN) with unusual and valuable properties that allows tissue-independent switching of the inflammatory cascade. Here, extraordinary durability of the anti-inflammatory agent allows, for the first time, the development of a 3D culture system that maintains the growth and cytoskeletal reorganization of brain tissue, while also facilitating the trophic behavior of brain cells for 22 d in vitro. Notably, this behavior was confirmed within an active scar site due to the unprecedented resilience to the presence of inflammatory cells and enzymes in the brain. Efficacy of the culture system is demonstrated via novel insights about inflammatory cell behavior, which would be impossible to obtain via in vivo experimentation.
Publisher: Wiley
Date: 17-04-2009
Publisher: MDPI AG
Date: 22-04-2022
DOI: 10.3390/IJMS23094646
Abstract: Clinical studies have provided evidence for dopamine (DA) cell replacement therapy in Parkinson’s Disease. However, grafts derived from foetal tissue or pluripotent stem cells (PSCs) remain heterogeneous, with a high proportion of non-dopaminergic cells, and display subthreshold reinnervation of target tissues, thereby highlighting the need to identify new strategies to improve graft outcomes. In recent work, Stromal Cell-Derived Factor-1 (SDF1), secreted from meninges, has been shown to exert many roles during ventral midbrain DA development and DA-directed differentiation of PSCs. Related, co-implantation of meningeal cells has been shown to improve neural graft outcomes, however, no direct evidence for the role of SDF1 in neural grafting has been shown. Due to the rapid degradation of SDF1 protein, here, we utilised a hydrogel to entrap the protein and sustain its delivery at the transplant site to assess the impact on DA progenitor differentiation, survival and plasticity. Hydrogels were fabricated from self-assembling peptides (SAP), presenting an epitope for laminin, the brain’s main extracellular matrix protein, thereby providing cell adhesive support for the grafts and additional laminin–integrin signalling to influence cell fate. We show that SDF1 functionalised SAP hydrogels resulted in larger grafts, containing more DA neurons, increased A9 DA specification (the subpopulation of DA neurons responsible for motor function) and enhanced innervation. These findings demonstrate the capacity for functionalised, tissue-specific hydrogels to improve the composition of grafts targeted for neural repair.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Springer Science and Business Media LLC
Date: 23-12-2016
Publisher: MDPI AG
Date: 21-06-2018
Publisher: IOP Publishing
Date: 27-03-2019
Publisher: Mary Ann Liebert Inc
Date: 02-2016
Abstract: The central nervous system has a limited capacity to regenerate, and thus, traumatic injuries or diseases often have devastating consequences. Therefore, there is a distinct need to develop alternative treatments that can achieve functional recovery without side effects currently observed with some pharmacological treatments. Combining biomaterials with pluripotent stem cells (PSCs), either embryonic or induced, has the potential to revolutionize the treatment of neurodegenerative diseases and traumatic injuries. Biomaterials can mimic the extracellular matrix and present a myriad of relevant biochemical cues through rational design or further functionalization. Biomaterials such as nanofibers and hydrogels, including self-assembling peptide (SAP) hydrogels can provide a superior cell culture environment. When these materials are then combined with PSCs, more accurate drug screening and disease modeling could be developed, and the generation of large number of cells with the appropriate phenotype can be achieved, for subsequent use in vitro. Biomaterials have also been shown to support endogenous cell growth after implantation, and, in particular, hydrogels and SAPs have effectively acted as cell delivery vehicles, increasing cell survival after transplantation. Few studies are yet to fully exploit the combination of PSCs and innovative biomaterials however, initial studies with neural stem cells, for ex le, are promising, and, hence, such a combination for use in vitro and in vivo is an exciting new direction for the field of neural regeneration.
Publisher: Wiley
Date: 03-2014
DOI: 10.1002/BIP.22469
Abstract: Nanomaterials are rich in potential, particularly for the formation of scaffolds that mimic the landscape of the host environment of the cell. This niche arises from the spatial organization of a series of biochemical and biomechanical signals. Self‐assembling peptides have emerged as an important tool in the development of functional (bio‐)nanomaterials these simple, easily synthesized subunits form structures which present the properties of these larger, more complex systems. Scaffolds based upon these nanofibrous matrices are promising materials for regenerative medicine as part of a new methodology in scaffold design where a “bottom‐up” approach is used in order to simulate the native cellular milieu. Importantly, SAPs hold the potential to be bioactive through the presentation of biochemical and biomechanical signals in a context similar to the natural extracellular matrix, making them ideal targets for providing structural and chemical support in a cellular context. Here, we discuss a new methodology for the presentation of biologically relevant epitopes through their effective presentation on the surface of the nanofibers. Here, we demonstrate that these signals have a direct effect on the viability of cells within a three‐dimensional matrix as compared with an unfunctionalized, yet mechanically and morphologically similar system. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 197–205, 2014.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1QM01010G
Abstract: Small-angle X-ray scattering is used to unpack the hidden structure of a gelatin methacryloyl (GelMA) biogel. We present insights regarding how the degree of functionalisation, crosslinked polymer conformation, nanoscale mesh size and macroscale mechanical properties are interlinked.
Publisher: The Optical Society
Date: 22-07-2016
DOI: 10.1364/BOE.7.003111
Publisher: American Chemical Society (ACS)
Date: 30-09-2021
Abstract: Additive manufacturing of metals using selective laser melting can create customized parts with various degrees of complexity and geometry for medical implants. However, challenges remain in accepting orthopedic implants due to the bio-inert surface of metal scaffolds, resulting in a lack of osseointegration. Here, we show that polycrystalline diamond (PCD) coatings on selective laser melted titanium (SLM-Ti) scaffolds can improve the cell-to-material interaction of osteoblasts. The results show that by controlling the uniformity of the diamond coatings, we can mediate the biological response of osteoblasts, such as cell adhesion, proliferation, and spreading. The osteoblasts show favorable cell adhesion and spreading on non-planar PCD-coated scaffolds compared to the un-coated SLM-Ti scaffold. This study plays an important role in understanding the key physicochemical behavior of bone cell growth on customized orthopedic implant materials.
Publisher: Springer Science and Business Media LLC
Date: 21-12-2008
Abstract: The production of functional molecular architectures through self-assembly is commonplace in biology, but despite advances, it is still a major challenge to achieve similar complexity in the laboratory. Self-assembled structures that are reproducible and virtually defect free are of interest for applications in three-dimensional cell culture, templating, biosensing and supramolecular electronics. Here, we report the use of reversible enzyme-catalysed reactions to drive self-assembly. In this approach, the self-assembly of aromatic short peptide derivatives provides a driving force that enables a protease enzyme to produce building blocks in a reversible and spatially confined manner. We demonstrate that this system combines three features: (i) self-correction--fully reversible self-assembly under thermodynamic control (ii) component-selection--the ability to lify the most stable molecular self-assembly structures in dynamic combinatorial libraries and (iii) spatiotemporal confinement of nucleation and structure growth. Enzyme-assisted self-assembly therefore provides control in bottom-up fabrication of nanomaterials that could ultimately lead to functional nanostructures with enhanced complexities and fewer defects.
Publisher: Wiley
Date: 16-11-2021
Publisher: Frontiers Media SA
Date: 06-01-2021
DOI: 10.3389/FNINS.2020.594818
Abstract: RXFP3 (relaxin-family peptide 3 receptor) is the cognate G-protein-coupled receptor for the neuropeptide, relaxin-3. RXFP3 is expressed widely throughout the brain, including the hypothalamus, where it has been shown to modulate feeding behavior and neuroendocrine activity in rodents. In order to better characterize its potential mechanisms of action, this study determined whether RXFP3 is expressed by dopaminergic neurons within the arcuate nucleus (ARC) and dorsomedial hypothalamus (DMH), in addition to the ventral tegmental area (VTA). Neurons that express RXFP3 were visualized in coronal brain sections from RXFP3-Cre/tdTomato mice, which express the tdTomato fluorophore within RXFP3-positive cells, and dopaminergic neurons in these areas were visualized by simultaneous immunohistochemical detection of tyrosine hydroxylase-immunoreactivity (TH-IR). Approximately 20% of ARC neurons containing TH-IR coexpressed tdTomato fluorescence, suggesting that RXFP3 can influence the dopamine pathway from the ARC to the pituitary gland that controls prolactin release. The ability of prolactin to reduce leptin sensitivity and increase food consumption therefore represents a potential mechanism by which RXFP3 activation influences feeding. A similar proportion of DMH neurons containing TH-IR expressed RXFP3-related tdTomato fluorescence, consistent with a possible RXFP3-mediated regulation of stress and neuroendocrine circuits. In contrast, RXFP3 was barely detected within the VTA. TdTomato signal was absent from the ARC and DMH in sections from Rosa26-tdTomato mice, suggesting that the cells identified in RXFP3-Cre/tdTomato mice expressed authentic RXFP3-related tdTomato fluorescence. Together, these findings identify potential hypothalamic mechanisms through which RXFP3 influences neuroendocrine control of metabolism, and further highlight the therapeutic potential of targeting RXFP3 in feeding-related disorders.
Publisher: Research Square Platform LLC
Date: 06-2022
DOI: 10.21203/RS.3.RS-50947/V1
Abstract: Injectable hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, as with other cell-laden transplantable materials, they suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here, we have engineered a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. This hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. The addition of myoglobin to the hydrogel resulted in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. Further development of this approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.NANO.2016.01.009
Abstract: The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications is the nanostructured scaffolds formed by epitope presenting minimalist self-assembled peptides these are bioactive on a cellular length scale, while presenting as an easily handled hydrogel. Here, we show that the assembly process can distribute an anti-inflammatory polysaccharide, fucoidan, localized to the nanofibers within the scaffold to create a biomaterial for cancer therapy. We show that it supports healthy cells, while inducing apoptosis in cancerous epithelial cells, as demonstrated by the significant down-regulation of gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications in local epithelial cancer immunotherapy and drug delivery.
Publisher: American Vacuum Society
Date: 11-02-2012
DOI: 10.1007/S13758-011-0002-X
Abstract: The fabrication of tissue engineering scaffolds is a well-established field that has gained recent prominence for the in vivo repair of a variety of tissue types. Recently, increasing levels of sophistication have been engineered into adjuvant scaffolds facilitating the concomitant presentation of a variety of stimuli (both physical and biochemical) to create a range of favourable cellular microenvironments. It is here that self-assembling peptide scaffolds have shown considerable promise as functional biomaterials, as they are not only formed from peptides that are physiologically relevant, but through molecular recognition can offer synergy between the presentation of biochemical and physio-chemical cues. This is achieved through the utilisation of a unique, highly ordered, nano- to microscale 3-D morphology to deliver mechanical and topographical properties to improve, augment or replace physiological function. Here, we will review the structures and forces underpinning the formation of self-assembling scaffolds, and their application in vivo for a variety of tissue types.
Publisher: American Chemical Society (ACS)
Date: 04-01-2006
DOI: 10.1021/JA056549L
Abstract: We demonstrate that proteases can be used to selectively trigger the self-assembly of peptide hydrogels via reversed hydrolysis.
Publisher: American Chemical Society (ACS)
Date: 13-06-2022
DOI: 10.1021/ACSBIOMATERIALS.2C00094
Abstract: Three-dimensional (3D) printing and 3D bioprinting are promising technologies for a broad range of healthcare applications from frontier regenerative medicine and tissue engineering therapies to pharmaceutical advancements yet must overcome the challenges of biocompatibility and resolution. Through comparison of traditional biofabrication methods with 3D (bio)printing, this review highlights the promise of 3D printing for the production of on-demand, personalized, and complex products that enhance the accessibility, effectiveness, and safety of drug therapies and delivery systems. In addition, this review describes the capacity of 3D bioprinting to fabricate patient-specific tissues and living cell systems (e.g., vascular networks, organs, muscles, and skeletal systems) as well as its applications in the delivery of cells and genes, microfluidics, and organ-on-chip constructs. This review summarizes how tailoring selected parameters (i.e., accurately selecting the appropriate printing method, materials, and printing parameters based on the desired application and behavior) can better facilitate the development of optimized 3D-printed products and how dynamic 4D-printed strategies (printing materials designed to change with time or stimulus) may be deployed to overcome many of the inherent limitations of conventional 3D-printed technologies. Comprehensive insights into a critical perspective of the future of 4D bioprinting, crucial requirements for 4D printing including the programmability of a material, multimaterial printing methods, and precise designs for meticulous transformations or even clinical applications are also given.
Publisher: Elsevier
Date: 2015
Publisher: Portland Press Ltd.
Date: 08-2021
DOI: 10.1042/EBC20200149
Abstract: Skeletal muscle is a functional tissue that accounts for approximately 40% of the human body mass. It has remarkable regenerative potential, however, trauma and volumetric muscle loss, progressive disease and aging can lead to significant muscle loss that the body cannot recover from. Clinical approaches to address this range from free-flap transfer for traumatic events involving volumetric muscle loss, to myoblast transplantation and gene therapy to replace muscle loss due to sarcopenia and hereditary neuromuscular disorders, however, these interventions are often inadequate. The adoption of engineering paradigms, in particular materials engineering and materials/tissue interfacing in biology and medicine, has given rise to the rapidly growing, multidisciplinary field of bioengineering. These methods have facilitated the development of new biomaterials that sustain cell growth and differentiation based on bionic biomimicry in naturally occurring and synthetic hydrogels and polymers, as well as additive fabrication methods to generate scaffolds that go some way to replicate the structural features of skeletal muscle. Recent advances in biofabrication techniques have resulted in significant improvements to some of these techniques and have also offered promising alternatives for the engineering of living muscle constructs ex vivo to address the loss of significant areas of muscle. This review highlights current research in this area and discusses the next steps required towards making muscle biofabrication a clinical reality.
Publisher: eLife Sciences Publications, Ltd
Date: 13-10-2020
DOI: 10.7554/ELIFE.56554
Abstract: Cytotoxic T lymphocytes (CTLs) are thought to arrive at target sites either via random search or following signals by other leukocytes. Here, we reveal independent emergent behaviour in CTL populations attacking tumour masses. Primary murine CTLs coordinate their migration in a process reminiscent of the swarming observed in neutrophils. CTLs engaging cognate targets accelerate the recruitment of distant T cells through long-range homotypic signalling, in part mediated via the diffusion of chemokines CCL3 and CCL4. Newly arriving CTLs augment the chemotactic signal, further accelerating mass recruitment in a positive feedback loop. Activated effector human T cells and chimeric antigen receptor (CAR) T cells similarly employ intra-population signalling to drive rapid convergence. Thus, CTLs recognising a cognate target can induce a localised mass response by lifying the direct recruitment of additional T cells independently of other leukocytes.
Publisher: MDPI AG
Date: 06-03-2023
DOI: 10.3390/GELS9030199
Abstract: Bioinspired self-assembly is a bottom-up strategy enabling biologically sophisticated nanostructured biogels that can mimic natural tissue. Self-assembling peptides (SAPs), carefully designed, form signal-rich supramolecular nanostructures that intertwine to form a hydrogel material that can be used for a range of cell and tissue engineering scaffolds. Using the tools of nature, they are a versatile framework for the supply and presentation of important biological factors. Recent developments have shown promise for many applications such as therapeutic gene, drug and cell delivery and yet are stable enough for large-scale tissue engineering. This is due to their excellent programmability—features can be incorporated for innate biocompatibility, biodegradability, synthetic feasibility, biological functionality and responsiveness to external stimuli. SAPs can be used independently or combined with other (macro)molecules to recapitulate surprisingly complex biological functions in a simple framework. It is easy to accomplish localized delivery, since they can be injected and can deliver targeted and sustained effects. In this review, we discuss the categories of SAPs, applications for gene and drug delivery, and their inherent design challenges. We highlight selected applications from the literature and make suggestions to advance the field with SAPs as a simple, yet smart delivery platform for emerging BioMedTech applications.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.CELREP.2017.07.069
Abstract: Stem cell transplants offer significant hope for brain repair following ischemic damage. Pre-clinical work suggests that therapeutic mechanisms may be multi-faceted, incorporating bone-fide circuit reconstruction by transplanted neurons, but also protection/regeneration of host circuitry. Here, we engineered hydrogel scaffolds to form "bio-bridges" within the necrotic lesion cavity, providing physical and trophic support to transplanted human embryonic stem cell-derived cortical progenitors, as well as residual host neurons. Scaffolds were fabricated by the self-assembly of peptides for a laminin-derived epitope (IKVAV), thereby mimicking the brain's major extracellular protein. Following focal ischemia in rats, scaffold-supported cell transplants induced progressive motor improvements over 9 months, compared to cell- or scaffold-only implants. These grafts were larger, exhibited greater neuronal differentiation, and showed enhanced electrophysiological properties reflective of mature, integrated neurons. Varying graft timing post-injury enabled us to attribute repair to both neuroprotection and circuit replacement. These findings highlight strategies to improve the efficiency of stem cell grafts for brain repair.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4RA13266A
Abstract: Hydrogels formed by the self-assembly of peptides are promising biomaterials. Here we demonstrate that the final material properties of a bioactive self assembled peptide system can be determined via control over the assembly conditions.
Publisher: MDPI AG
Date: 06-04-2022
DOI: 10.3390/GELS8040224
Abstract: The defined self-assembly of peptides (SAPs) into nanostructured bioactive hydrogels has great potential for repairing traumatic brain injuries, as they maintain a stable, homeostatic environment at an injury site, preventing further degeneration. They also present a bespoke platform to restore function via the naturalistic presentation of therapeutic proteins, such as stromal-cell-derived factor 1 (SDF-1), expressed by meningeal cells. A key challenge to the use of the SDF protein, however, is its rapid diffusion and degradation. Here, we engineered a homeostatic hydrogel produced by incorporating recombinant SDF-1 protein within a self-assembled peptide hydrogel to create a supportive milieu for transplanted cells. Our hydrogel can concomitantly deliver viable primary neural progenitor cells and sustained active SDF-1 to support the nascent graft, resulting in increased neuronal differentiation. Moreover, this homeostatic hydrogel can ensure a healthy and larger graft core without impeding neuronal fiber growth and innervation. These findings demonstrate the regenerative potential of these hydrogels to improve the integration of grafted cells to treat neural injuries and diseases.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3SM27758E
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4TB01391C
Abstract: Functionalized N -fluorenylmethyloxycarbonyl self-assembling peptides are biocompatible in vivo , demonstrating their utility as a cell delivery vehicle for tissue engineering.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0MH00398K
Abstract: Self-assembling peptide hydrogels can effectively transport, hold and release therapeutic molecules in a spatially and temporally controlled manner and, in doing so, improve anti-cancer drug efficacy while reducing non-specific toxicity.
Publisher: MDPI AG
Date: 15-10-2021
DOI: 10.3390/GELS7040171
Abstract: For decades, the study of tissue-engineered skeletal muscle has been driven by a clinical need to treat neuromuscular diseases and volumetric muscle loss. The in vitro fabrication of muscle offers the opportunity to test drug-and cell-based therapies, to study disease processes, and to perhaps, one day, serve as a muscle graft for reconstructive surgery. This study developed a biofabrication technique to engineer muscle for research and clinical applications. A bioprinting protocol was established to deliver primary mouse myoblasts in a gelatin methacryloyl (GelMA) bioink, which was implanted in an in vivo chamber in a nude rat model. For the first time, this work demonstrated the phenomenon of myoblast migration through the bioprinted GelMA scaffold with cells spontaneously forming fibers on the surface of the material. This enabled advanced maturation and facilitated the connection between incoming vessels and nerve axons in vivo without the hindrance of a scaffold material. Immunohistochemistry revealed the hallmarks of tissue maturity with sarcomeric striations and peripherally placed nuclei in the organized bundles of muscle fibers. Such engineered muscle autografts could, with further structural development, eventually be used for surgical reconstructive purposes while the methodology presented here specifically has wide applications for in vitro and in vivo neuromuscular function and disease modelling.
Publisher: Elsevier BV
Date: 03-2019
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.ACTBIO.2016.04.038
Abstract: The nanofibrillar structures that underpin self-assembling peptide (SAP) hydrogels offer great potential for the development of finely tuned cellular microenvironments suitable for tissue engineering. However, biofunctionalisation without disruption of the assembly remains a key issue. SAPS present the peptide sequence within their structure, and studies to date have typically focused on including a single biological motif, resulting in chemically and biologically homogenous scaffolds. This limits the utility of these systems, as they cannot effectively mimic the complexity of the multicomponent extracellular matrix (ECM). In this work, we demonstrate the first successful co-assembly of two biologically active SAPs to form a coassembled scaffold of distinct two-component nanofibrils, and demonstrate that this approach is more bioactive than either of the in idual systems alone. Here, we use two bioinspired SAPs from two key ECM proteins: Fmoc-FRGDF containing the RGD sequence from fibronectin and Fmoc-DIKVAV containing the IKVAV sequence from laminin. Our results demonstrate that these SAPs are able to co-assemble to form stable hybrid nanofibres containing dual epitopes. Comparison of the co-assembled SAP system to the in idual SAP hydrogels and to a mixed system (composed of the two hydrogels mixed together post-assembly) demonstrates its superior stable, transparent, shear-thinning hydrogels at biological pH, ideal characteristics for tissue engineering applications. Importantly, we show that only the coassembled hydrogel is able to induce in vitro multinucleate myotube formation with C2C12 cells. This work illustrates the importance of tissue engineering scaffold functionalisation and the need to develop increasingly advanced multicomponent systems for effective ECM mimicry. Successful control of stem cell fate in tissue engineering applications requires the use of sophisticated scaffolds that deliver biological signals to guide growth and differentiation. The complexity of such processes necessitates the presentation of multiple signals in order to effectively mimic the native extracellular matrix (ECM). Here, we establish the use of two biofunctional, minimalist self-assembling peptides (SAPs) to construct the first co-assembled SAP scaffold. Our work characterises this construct, demonstrating that the physical, chemical, and biological properties of the peptides are maintained during the co-assembly process. Importantly, the coassembled system demonstrates superior biological performance relative to the in idual SAPs, highlighting the importance of complex ECM mimicry. This work has important implications for future tissue engineering studies.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2CC15578H
Abstract: Micropatterning of surfaces with varying chemical, physical and topographical properties usually requires a number of fabrication steps. Herein, we describe a micropatterning technique based on plasma enhanced chemical vapour deposition (PECVD) that deposits both protein resistant and protein repellent surface chemistries in a single step. The resulting multifunctional, selective surface chemistries are capable of spatially controlled protein adhesion, geometric confinement of cells and the site specific confinement of enzyme mediated peptide self-assembly.
Publisher: American Vacuum Society
Date: 21-09-2018
DOI: 10.1116/1.5042693
Abstract: This paper critically reviews the current evidence of research in biomedical applications of selenium nanoparticles (SeNPs) and their effects at cellular and tissue levels. In recent years, interest in SeNPs as a natural trace element nanomaterial for nanomedicine has resulted in a number of studies evaluating their bioactivities, such as anticancer, antimicrobial, and antioxidant properties. Significant data have been generated to demonstrate the effectiveness of SeNPs alone or in combination with other reagents. Their activities are demonstrated through in vitro and in vivo experimentation yet, the levels of efficacy need to be improved, particularly when compared with those of pharmaceutical drugs (such as antibiotics and cytotoxic chemotherapeutic drugs). However, promising evidence suggests decreased toxicity when using SeNPs, and more importantly their ability to perform as an interfacing biomaterial with cells and tissues. SeNPs have demonstrated unique antibacterial properties: they inhibit bacterial adhesion, growth, and/or quorum sensing and as a result prevent biofilm formation on medical devices, to name a few. Therefore, as with other nanomaterials, SeNPs warrant further study as part of the biomaterial-based therapeutic toolkit as an alternative to traditional pharmaceutical agents. This paper will provide a succinct review of recent studies on SeNPs to critically assess the findings in the light of effectiveness, particularly highlighting the roles of the cellular interface. Finally, an outlook of the potential of SeNPs will be presented to highlight the need for more intensive studies of material stability, mechanistic understanding at subcellular levels, and investigations into their combinational and/or synergistic effects with other bioactive reagents including pharmaceutical drugs.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.BIOMATERIALS.2011.03.078
Abstract: We demonstrate the distribution of the important extracellular matrix protein laminin in a novel biomaterial consisting of a hydrogel underpinned by nanofibrillar networks. These are formed by the immobilised enzyme mediated self-assembly of fmoc-L(3) (9-fluorenylmethoxycarbonyl-tri-leucine). The peptide assembly yields nanofibrils formed of β-sheets that are locked together via π-stacking interactions. This ordering allows the localisation of the peptide sidechains on the surface, creating a hydrophobic environment. This induces the formation of bundles of these nanofibrils producing a clear hydrogel. This mechanism enables the three dimensional distribution of laminin throughout the network via supramolecular interactions. These forces favour the formation and improve the order of the network itself, as observed by spectroscopic and mechanical testing. In order to test the stability and suitability of this class of material for in vivo applications, we utilise microinjection to deliver the biomaterial under fine spatial control into a dystrophic zebrafish model organism, which lacks laminin as a result of a genetic mutation. Using confocal and transmission electron microscopy, we confirm that the biomaterial remains stable structurally, and is confined spatially to the site of injection.
Publisher: Springer Science and Business Media LLC
Date: 25-08-2016
DOI: 10.1007/S11064-015-1697-8
Abstract: Astrocytes execute essential functions in the healthy CNS, whilst also being implicated as a limitation to functional regeneration and repair after injury. They respond to injury to minimize damage to healthy tissue whilst also attempting to seal the broken blood-brain-barrier, however, they impede recovery if they are persistent and form a permanent scar in the injured brain. As such, it is of great importance to understand the mechanism underlying the astrocytic response to injury, and this understanding is currently limited by the in vitro environments available to scientists. Biomaterials such as nanofibres and hydrogels offer great potential for the development of superior, 3D cell culture environments in which to study astrocyte behavior and phenotype. The implementation of such in vitro environments with a particularly interdisciplinary approach can improve the field's understanding of astrocytes, their role in central nervous system inflammation, and elucidate potential strategies to achieve functional regeneration.
Publisher: Springer International Publishing
Date: 2017
DOI: 10.1007/978-3-319-66095-0_5
Abstract: The ability to fabricate artificial tissue constructs through the controlled organisation of cells, structures and signals within a biomimetic scaffold offers significant promise to the field of regenerative medicine, drug delivery and tissue engineering. Advances in additive manufacturing technologies have facilitated the printing of spatially defined cell-laden artificial tissue constructs capable of providing biomimetic spatiotemporal presentation of biological and physical cues to cells in a designed multicomponent structure. Despite significant progress in the field of bioprinting, a key challenge remains in developing and utilizing materials that can adequately recapitulate the complexities of the native extracellular matrix on a nanostructured, chemical level during the printing process. This gives rise to the need for suitable materials - particularly in establishing effective control over cell fate, tissue vascularization and innervation. Recently, significant interested has been invested into developing candidate materials using protein and peptide-derived biomaterials. The ability of these materials to form highly printable hydrogels which are reminiscent of the native ECM has seen significant use in a variety of regenative applications, including both organ bioprinting and non-organ bioprinting. Here, we discuss the emerging technologies for peptide-based bioprinting applications, highlighting bioink development and detailing bioprinter processors. Furthermore, this work presents application specific, peptide-based bioprinting approaches, and provides insight into current limitations and future perspectives of peptide-based bioprinting techniques.
Publisher: American Chemical Society (ACS)
Date: 14-06-2021
Publisher: Hindawi Limited
Date: 27-11-2018
DOI: 10.1002/TERM.2582
Abstract: Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease. The neural tissue-specific SAP, Fmoc-DIKVAV, demonstrated sustained release of glial cell line derived neurotrophic factor, up to 172 hr after gel loading. This represents a significant advance in drug delivery, because its lifetime in phosphate buffered saline was less than 1 hr. In vivo transplantation of neural progenitor cells, together with our growth factor-loaded material, into the injured brain improved graft survival compared with cell transplants alone. We show for the first time the use of minimalist Fmoc-SAP in an in vivo disease model for sustaining the delivery of neurotrophic growth factors, facilitating their spatial and temporal delivery in vivo, whilst also providing an enhanced niche environment for transplanted cells.
Publisher: American Chemical Society (ACS)
Date: 02-03-2022
Publisher: Wiley
Date: 30-11-2018
Abstract: Tissue engineering scaffolds are designed to mimic physical, chemical, and biological features of the extracellular matrix, thereby providing a constant support that is crucial to improved regenerative medicine outcomes. Beyond mechanical and structural support, the next generation of these materials must also consider the more dynamic presentation and delivery of drugs or growth factors to guide new and regenerating tissue development. These two aspects are explored expansively separately, but they must interact synergistically to achieve optimal regeneration. This review explores common tissue engineering materials types, electrospun polymers and hydrogels, and strategies used for incorporating drug delivery systems into these scaffolds.
Publisher: Informa UK Limited
Date: 13-12-2015
Publisher: Elsevier BV
Date: 06-2022
Publisher: American Chemical Society (ACS)
Date: 02-2018
DOI: 10.1021/ACS.BIOMAC.7B01632
Abstract: The material properties of natural tissues, such as skeletal muscle, are highly sophisticated and are synthetically challenging to mimic. Using natural biomacromolecules to functionalize self-assembled peptide (SAP) hydrogels has the potential to increase the utility of these materials by more closely reproducing the natural cellular environment. Here, to demonstrate that a conserved co-assembly pathway can retain distinct function, the biocompatible peptide derivative Fmoc-FRGDF was co-assembled with either a sulfated polysaccharide, fucoidan, or the provisional matrix proteoglycan, versican. Our results demonstrate that thermodynamically driven co-assembly with biologically active macromolecules is facile, stable, and does not affect the final assembled nanostructure. Biologically, the incorporation of these functionally distinct molecules had no effect on C2C12 myoblast proliferation and viability but strongly altered their morphology. The surface area of myoblasts cultured on the fucoidan scaffold was reduced at 24 and 72 h post seeding, with a reduction in the formation of multinucleated syncytia. Myoblasts cultured on versican scaffolds were smaller compared to cells grown on the empty vector scaffolds at 24 h but not 72 h post seeding, with multinucleated syncytia formation being unaffected. This work allows programmed and distinct morphological effects of cell behavior, paving the way for further mechanistic studies.
Publisher: Springer Science and Business Media LLC
Date: 06-07-2017
DOI: 10.1038/S41598-017-04643-3
Abstract: Enabling control over macromolecular ordering and the spatial distribution of structures formed via the mechanisms of molecular self-assembly is a challenge that could yield a range of new functional materials. In particular, using the self-assembly of minimalist peptides, to drive the incorporation of large complex molecules will allow a functionalization strategy for the next generation of biomaterial engineering. Here, for the first time, we show that co-assembly with increasing concentrations of a highly charged polysaccharide, fucoidan, the microscale ordering of Fmoc-FRGDF peptide fibrils and subsequent mechanical properties of the resultant hydrogel can be easily and effectively manipulated without disruption to the nanofibrillar structure of the assembly.
Publisher: Wiley
Date: 2010
DOI: 10.1002/BIP.21346
Abstract: This review article covers recent developments in the use of enzyme-catalyzed reactions to control molecular self-assembly (SA), an area that merges the advantages of biocatalysis with soft materials self-assembly. This approach is attractive because it combines biological (chemo-, regio-, and enantio-) selectivity with the versatility of bottom up nanofabrication through dynamic SA. We define enzyme-assisted SA (e-SA) as the production of molecular building blocks from nonassembling precursors via enzymatic catalysis, where molecular building blocks form ordered structures via noncovalent interactions. The molecular design of SA precursors is discussed in terms of three key components related to (i) enzyme recognition, (ii) molecular switching mechanisms, and (iii) supramolecular interactions that underpin SA. This is followed by a discussion of a number of unique features of these systems, including spatiotemporal control of nucleation and structure growth, the possibility of controlling mechanical properties and the defect correcting and component selecting capabilities of systems that operate under thermodynamic control. Applications in biomedicine (biosensing, controlled release, matrices for wound healing, controlling cell fate by gelation) and bio(nano)technology (biocatalysts immobilization, nanofabrication, templating, and intracellular imaging) are discussed. Overall, e-SA allows for unprecedented control over SA processes and provides a step forward toward production of nanostructures of higher complexity and with fewer defects as desired for next generation nanomaterials.
Publisher: Wiley
Date: 19-12-2019
Publisher: Mary Ann Liebert Inc
Date: 08-2021
Publisher: IOP Publishing
Date: 12-08-2016
DOI: 10.1088/0957-4484/27/38/385102
Abstract: Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2013
End Date: 12-2016
Amount: $360,000.00
Funder: Australian Research Council
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