ORCID Profile
0000-0002-5428-7575
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Rheology | Biomaterials | Biomedical Engineering
Expanding Knowledge in the Physical Sciences | Expanding Knowledge in Engineering | Plastics in Primary Forms |
Publisher: Wiley
Date: 11-2020
Publisher: Wiley
Date: 26-09-2023
Publisher: IOP Publishing
Date: 12-04-2022
Abstract: Recently developed modular bioassembly techniques hold tremendous potential in tissue engineering and regenerative medicine, due to their ability to recreate the complex microarchitecture of native tissue. Here, we developed a novel approach to fabricate hybrid tissue-engineered constructs adopting high-throughput microfluidic and 3D bioassembly strategies. Osteochondral tissue fabrication was adopted as an ex le in this study, because of the challenges in fabricating load bearing osteochondral tissue constructs with phenotypically distinct zonal architecture. By developing cell-instructive chondrogenic and osteogenic bioink microsphere modules in high-throughput, together with precise manipulation of the 3D bioassembly process, we successfully fabricated hybrid engineered osteochondral tissue in vitro with integrated but distinct cartilage and bone layers. Furthermore, by encapsulating allogeneic umbilical cord blood-derived mesenchymal stromal cells, and demonstrating chondrogenic and osteogenic differentiation, the hybrid biofabrication of hydrogel microspheres in this 3D bioassembly model offers potential for an off-the-shelf, single-surgery strategy for osteochondral tissue repair.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0BM01010C
Abstract: Silk photo-lyogels fabricated by di-tyrosine photo-crosslinking and ice-templating silk fibroin on 3D printed templates toward in situ tissue engineering applications.
Publisher: SAGE Publications
Date: 21-02-2022
DOI: 10.1177/03635465211072557
Abstract: The lack of healing at the repaired tendon-bone interface is an important cause of failure after rotator cuff repair. While augmentation with growth factors (GFs) has demonstrated promise, the ideal combination must target all 3 tissue types at the tendon-bone interface. The GF combination of transforming growth factor beta 1, Insulin-like growth factor 1, and parathyroid hormone will promote tenocyte proliferation and differentiation and improve the biomechanical and histological quality of the repaired tendon-bone interface. Controlled laboratory study. In vitro, human tenocytes were cultured in the presence of the GF combination for 72 hours, and cell growth assays and the expression of genes specific to tendon, cartilage, and bone were analyzed. In vivo, adult rats (N = 46) underwent detachment and repair of the left supraspinatus tendon. A PVA-tyramine gel was used to deliver the GF combination to the tendon-bone interface. Histological, biomechanical, and RNA microarray analysis was performed at 6 and 12 weeks after surgery. Immunohistochemistry for type II and X collagen was performed at 12 weeks. When treated with the GF combination in vitro, human tenocytes proliferated 1.5 times more than control ( P = .04). The expression of scleraxis increased 65-fold ( P = .013). The expression of Sox-9 ( P = .011), type I collagen ( P = .021), fibromodulin ( P = .0075), and biglycan ( P = .010) was also significantly increased, while the expression of PPARγ was decreased ( P = .007). At 6 and 12 weeks postoperatively, the quality of healing on histology was significantly higher in the GF group, with the formation of a more mature tendon-bone interface, as confirmed by immunohistochemistry for type II and X collagen. The GF group achieved a load at failure and Young modulus .5 times higher at both time points. Microarrays at 6 weeks demonstrated upregulation of genes involved in leukocyte aggregation ( S100A8, S100A9) and tissue mineralization ( Bglap, serglycin, Fam20c). The GF combination promoted protendon and cartilage responses in human tenocytes in vitro it also improved the histological appearance and mechanical properties of the repair in vivo. Microarrays of the tendon-bone interface identified inflammatory and mineralization pathways affected by the GF combination, providing novel therapeutic targets for further research. The use of this GF combination is translatable to patients and may improve healing after rotator cuff repair.
Publisher: Wiley
Date: 24-03-2022
Abstract: The field of bioprinting has made significant advancements in recent years and allowed for the precise deposition of biomaterials and cells. However, within this field lies a major challenge, which is developing high resolution constructs, with complex architectures. In an effort to overcome these challenges a biofabrication technique known as vat polymerization is being increasingly investigated due to its high fabrication accuracy and control of resolution (µm scale). Despite the progress made in developing hydrogel precursors for bioprinting techniques, such as extrusion‐based bioprinting, there is a major lack in developing hydrogel precursor bioresins for vat polymerization. This is due to the specific unique properties and characteristics required for vat polymerization, from lithography to the latest volumetric printing. This is of major concern as the shortage of bioresins available has a significant impact on progressing this technology and exploring its full potential, including speed, resolution, and scale. Therefore, this review discusses the key requirements that need to be addressed in successfully developing a bioresin. The influence of monomer architecture and bioresin composition on printability is described, along with key fundamental parameters that can be altered to increase printing accuracy. Finally, recent advancements in bioresins are discussed together with future directions.
Publisher: Elsevier BV
Date: 12-2021
Publisher: European Cells and Materials
Date: 21-06-2018
DOI: 10.22203/ECM.V035A23
Publisher: IOP Publishing
Date: 12-06-2019
Abstract: Bioprinting of living cells is rapidly developing as an advanced biofabrication approach to engineer tissues. Bioinks can be extruded in three-dimensions (3D) to fabricate complex and hierarchical constructs for implantation. However, a lack of functionality can often be attributed to poor bioink properties. Indeed, advanced bioinks encapsulating living cells should: (i) present optimal rheological properties and retain 3D structure post fabrication, (ii) promote cell viability and support cell differentiation, and (iii) localise proteins of interest (e.g. vascular endothelial growth factor (VEGF)) to stimulate encapsulated cell activity and tissue ingrowth upon implantation. In this study, we present the results of the inclusion of a synthetic nanoclay, Laponite
Publisher: Wiley
Date: 12-01-2023
Abstract: Sacrificial printing allows introduction of architectural cues within engineered tissue constructs. This strategy adopts the use of a 3D‐printed sacrificial ink that is embedded within a bulk hydrogel which is subsequently dissolved to leave open‐channels. However, current conventional sacrificial inks do not recapitulate the dynamic nature of tissue development, such as the temporal presentation of architectural cues matching cellular requirements during different stages of maturation. To address this limitation, a new class of sacrificial inks is developed that exhibits tailorable and programmable delayed dissolution profiles (1–17 days), by exploiting the unique ability of the ruthenium complex and sodium persulfate initiating system to crosslink native tyrosine groups present in non‐chemically modified gelatin. These novel sacrificial inks are also shown to be compatible with a range of biofabrication technologies, including extrusion‐based printing, digital‐light processing, and volumetric bioprinting. Further embedding these sacrificial templates within cell‐laden bulk hydrogels displays precise control over the spatial and temporal introduction of architectural features into cell‐laden hydrogel constructs. This approach demonstrates the unique capacity of delaying dissolution of sacrificial inks to modulate cell behavior, improving the deposition of mineralized matrix and capillary‐like network formation in osteogenic and vasculogenic culture, respectively.
Publisher: Mary Ann Liebert Inc
Date: 08-2023
Publisher: Wiley
Date: 24-06-2020
DOI: 10.1111/JCMM.15492
Publisher: Cold Spring Harbor Laboratory
Date: 03-07-2023
DOI: 10.1101/2023.06.29.546799
Abstract: The study of in vitro models of breast cancer is crucial for understanding and treating the malignancy in patients, with 3D in vitro models providing researchers with more biomimetic systems to overcome limitations of current to 2D cultures and in vivo animal models. Ex vivo patient tissues have shown that malignant breast tissues are stiffer than healthy or benign tissues, and that the stiffness corresponds with increasing tumour grade. Stiffening of the breast tumour environment alters tumour cell phenotype and facilitates tumour progression, invasion and metastasis. Better understanding of the relationship between extracellular matrix stiffness and breast cancer cell phenotype, and how that is important in the initiation of metastasis, should lead to designing 3D models that mimic the breast tumour microenvironment at different stages of breast cancer progression. This study investigated phenotypic response of two breast cancer cell lines that are representative of clinical breast cancer subtypes (MCF7, Luminal A MDA-MB-231, Triple Negative Breast Cancer) in gelatin-methacryloyl (GelMA) hydrogels of varying stiffness. A visible light photoinitiation system was adopted to provide a tuneable photocrosslinking platform to systematically control hydrogel stiffness and tumour microenvironment. This allowed rapid fabrication of biocompatible hydrogels supporting high cell viability over long-term culture. The impact of a clinically relevant range of microenvironmental stiffness on breast cancer cell behaviour and phenotype was examined over a 21-day culture period using GelMA hydrogels. Results showed that MCF7 cells cultured for 21 days in high stiffness hydrogels (10 wt% 28 kPa) responded by downregulating the epithelial marker E-cadherin and upregulating mesenchymal markers N-cadherin and Vimentin, whereas MDA-MB-231 cells showed no changes in EMT-markers when cultured in hydrogels of corresponding stiffness (10 wt% 33 kPa). Culturing both cell lines in soft hydrogels (5 wt% 11 kPa) maintained their phenotype over 21 days, highlighting the importance of controlling hydrogel mechanical properties when studying breast cancer cell phenotype.
Publisher: MDPI AG
Date: 10-04-2022
DOI: 10.3390/JFB13020041
Abstract: Epigenetic approaches using the histone deacetylase 2 and 3 inhibitor-MI192 have been reported to accelerate stem cells to form mineralised tissues. Gelatine methacryloyl (GelMA) hydrogels provide a favourable microenvironment to facilitate cell delivery and support tissue formation. However, their application for bone repair is limited due to their low mechanical strength. This study aimed to investigate a GelMA hydrogel reinforced with a 3D printed scaffold to support MI192-induced human bone marrow stromal cells (hBMSCs) for bone formation. Cell culture: The GelMA (5 wt%) hydrogel supported the proliferation of MI192-pre-treated hBMSCs. MI192-pre-treated hBMSCs within the GelMA in osteogenic culture significantly increased alkaline phosphatase activity (p ≤ 0.001) compared to control. Histology: The MI192-pre-treated group enhanced osteoblast-related extracellular matrix deposition and mineralisation (p ≤ 0.001) compared to control. Mechanical testing: GelMA hydrogels reinforced with 3D printed poly(ethylene glycol)-terephthalate oly(butylene terephthalate) (PEGT/PBT) scaffolds exhibited a 1000-fold increase in the compressive modulus compared to the GelMA alone. MI192-pre-treated hBMSCs within the GelMA–PEGT/PBT constructs significantly enhanced extracellular matrix collagen production and mineralisation compared to control (p ≤ 0.001). These findings demonstrate that the GelMA–PEGT/PBT construct provides enhanced mechanical strength and facilitates the delivery of epigenetically-activated MSCs for bone augmentation strategies.
Publisher: Wiley
Date: 25-10-2017
Abstract: Multicomponent gelatin-methacryloyl (GelMA) hydrogels are regularly adopted for cartilage tissue engineering (TE) applications, where optimizing chemical modifications for preserving biofunctionality is often overlooked. This study investigates the biological effect of two different modification methods, methacrylation and thiolation, to copolymerize GelMA and heparin. The native bioactivity of methacrylated heparin (HepMA) and thiolated heparin (HepSH) is evaluated via thromboplastin time and heparan sulfate-deficient myeloid cell-line proliferation assay, demonstrating that thiolation is superior for preserving anticoagulation and growth factor signaling capacity. Furthermore, incorporating either HepMA or HepSH in chondrocyte-laden GelMA hydrogels, cultured for 5 weeks under chondrogenic conditions, promotes cell viability and chondrocyte phenotype. However, only GelMA-HepSH hydrogels yield significantly greater differentiation and matrix deposition in vitro compared to GelMA. This study demonstrates that thiol-ene chemistry offers a favorable strategy for incorporating bioactives into gelatin hydrogels as compared to methacrylation while furthermore highlighting GelMA-HepSH hydrogels as candidates for cartilage TE applications.
Publisher: MDPI AG
Date: 12-02-2023
DOI: 10.3390/NANO13040705
Abstract: There is a need to develop bifunctional scaffolds that provide antibacterial protection while encouraging host cell attachment roliferation. This study evaluates HyStem®-C, and photo-cross-linked GelMA hydrogels for encapsulation and stabilisation of silver nanoparticles (AgNPs). We studied the behaviour of AgNPs and matrix interactions within both hydrogel systems. The cell viability of encapsulated human gingival fibroblasts (HGFs) was determined by Prestoblue® assay and live/dead staining. The release of AgNPs was monitored by inductively coupled plasma–mass spectroscopy. The antibacterial properties of the GelMA-AgNP constructs were determined using disc diffusion. Even distribution of AgNPs in GelMA induced a significant decrease in cell viability (p 0.0001), whereas AgNP aggregates did not induce cytotoxicity in HyStem®-C. AgNPs doses ≥ 0.5 µg/mL in GelMA were significantly toxic to the HGFs (p 0.0001). The release of AgNPs from GelMA after 48 h was 20% w/w for 0.1 µg/mL and 51% for 100 µg/mL of AgNPs. At ≥5 µg/mL, a significant intra-construct bactericidal effect was observed. The disc diffusion assay shows that GelMA-incorporated AgNPs were found to be effective against both Escherichia coli and Staphylococcus aureus at 50 and 100 µg/mL, respectively. Visible photo-cross-linked GelMA stably incorporated AgNPs to provide an antimicrobial regenerative construct for oral applications.
Publisher: Wiley
Date: 30-04-2020
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.TIBTECH.2017.10.015
Abstract: Biofabrication holds the potential to generate constructs that more closely recapitulate the complexity and heterogeneity of tissues and organs than do currently available regenerative medicine therapies. Such constructs can be applied for tissue regeneration or as in vitro 3D models. Biofabrication is maturing and growing, and scientists with different backgrounds are joining this field, underscoring the need for unity regarding the use of terminology. We therefore believe that there is a compelling need to clarify the relationship between the different concepts, technologies, and descriptions of biofabrication that are often used interchangeably or inconsistently in the current literature. Our objective is to provide a guide to the terminology for different technologies in the field which may serve as a reference for the biofabrication community.
Publisher: IOP Publishing
Date: 08-01-2016
DOI: 10.1088/1758-5090/8/1/013001
Abstract: Biofabrication is an evolving research field that has recently received significant attention. In particular, the adoption of Biofabrication concepts within the field of Tissue Engineering and Regenerative Medicine has grown tremendously, and has been accompanied by a growing inconsistency in terminology. This article aims at clarifying the position of Biofabrication as a research field with a special focus on its relation to and application for Tissue Engineering and Regenerative Medicine. Within this context, we propose a refined working definition of Biofabrication, including Bioprinting and Bioassembly as complementary strategies within Biofabrication.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 04-2009
Publisher: Wiley
Date: 25-12-2023
Abstract: To streamline the drug discovery pipeline, there is a pressing need for preclinical models which replicate the complexity and scale of native tumors. While there have been advancements in the formation of microscale tumor units, these models are cell‐line dependent, time‐consuming and have not improved clinical trial success rates. In this study, two methods for generating 3D tumor microenvironments are compared, rapidly fabricated hydrogel microspheres and traditional cell‐dense spheroids. These modules are then bioassembled into 3D printed thermoplastic scaffolds, using an automated biofabrication process, to form tumor‐scale models. Modules are formed with SKOV3 and HFF cells as monocultures and cocultures, and the fabrication efficiency, cell architecture, and drug response profiles are characterized, both as single modules and as multimodular constructs. Cell‐encapsulated Gel‐MA microspheres are fabricated with high‐reproducibility and dimensions necessary for automated tumor‐scale bioassembly regardless of cell type, however, only cocultured spheroids form compact modules suitable for bioassembly. Chemosensitivity assays demonstrate the reduced potency of doxorubicin in coculture bioassembled constructs and a ≈five‐fold increase in drug resistance of cocultured cells in 3D modules compared with 2D monolayers. This bioassembly system is efficient and tailorable so that a variety of relevant‐sized tumor constructs could be developed to study tumorigenesis and modernize drug discovery.
Publisher: IEEE
Date: 08-2010
Publisher: Wiley
Date: 26-07-2021
Abstract: As emerging therapeutic factors, extracellular vesicles (EVs) offer significant potential for myocardial infarction (MI) treatment. Current delivery approaches for EVs involve either intra‐myocardial or intravenous injection, where both have inherent limitations for downstream clinical applications such as secondary tissue injury and low delivery efficiency. Herein, an injection‐free approach for delivering EVs onto the heart surface to treat MI is proposed. By spraying a mixture of EVs, gelatin methacryloyl (GelMA) precursors, and photoinitiators followed by visible light irradiation for 30 s, EVs are physically entrapped within the GelMA hydrogel network covering the surface of the heart, resulting in an enhanced retention rate. Moreover, EVs are gradually released from the hydrogel network through a combination of diffusion and/or enzymatic degradation of the hydrogel, and they are effectively taken up by the sprayed tissue area. More importantly, the released EVs further migrate deep into myocardium tissue, which exerts an improved therapeutic effect. In an MI‐induced mice model, the group treated with EVs‐laden GelMA hydrogels shows significant recovery in cardiac function after 4 weeks. The work demonstrates a new strategy for delivering EVs into cardiac tissues for MI treatment in a localized manner with high retention.
Publisher: AIP Publishing
Date: 03-2021
DOI: 10.1063/5.0015093
Publisher: American Chemical Society (ACS)
Date: 12-08-2016
Publisher: Elsevier BV
Date: 06-2020
Publisher: IOP Publishing
Date: 17-02-2014
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.TIBTECH.2021.04.006
Abstract: Autologous fat grafting offers significant promise for the repair of soft tissue deformities however, high resorption rates indicate that engineered solutions are required to improve adipose tissue (AT) survival. Advances in material development and biofabrication have laid the foundation for the generation of functional AT constructs however, a balance needs to be struck between clinically feasible delivery and improved structural integrity of the grafts. A new approach combining the objectives from both the clinical and research communities will assist in developing morphologically and genetically mature AT constructs, with controlled spatial arrangement and increased potential for neovascularization. In a rapidly progressing field, this review addresses research in both the preclinical and bioengineering domains and assesses their ability to resolve functional challenges.
Publisher: Wiley
Date: 26-04-2019
Abstract: In this study, the cyto-compatibility and cellular functionality of cell-laden gelatin-methacryloyl (Gel-MA) hydrogels fabricated using a set of photo-initiators which absorb in 400-450 nm of the visible light range are investigated. Gel-MA hydrogels cross-linked using ruthenium (Ru) and sodium persulfate (SPS), are characterized to have comparable physico-mechanical properties as Gel-MA gels photo-polymerized using more conventionally adopted photo-initiators, such as 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propan-1-one (Irgacure 2959) and lithium phenyl(2,4,6-trimethylbenzoyl) phosphinate (LAP). It is demonstrated that the Ru/SPS system has a less adverse effect on the viability and metabolic activity of human articular chondrocytes encapsulated in Gel-MA hydrogels for up to 35 days. Furthermore, cell-laden constructs cross-linked using the Ru/SPS system have significantly higher glycosaminoglycan content and re-differentiation capacity as compared to cells encapsulated using I2959 and LAP. Moreover, the Ru/SPS system offers significantly greater light penetration depth as compared to the I2959 system, allowing thick (10 mm) Gel-MA hydrogels to be fabricated with homogenous cross-linking density throughout the construct. These results demonstrate the considerable advantages of the Ru/SPS system over traditional UV polymerizing systems in terms of clinical relevance and practicability for applications such as cell encapsulation, biofabrication, and in situ cross-linking of injectable hydrogels.
Publisher: MDPI AG
Date: 05-06-2021
Abstract: Recent advances highlight the potential of photopolymerizable allylated gelatin (GelAGE) as a versatile hydrogel with highly tailorable properties. It is, however, unknown how different photoinitiating system affects the stability, gelation kinetics and curing depth of GelAGE. In this study, sol fraction, mass swelling ratio, mechanical properties, rheological properties, and curing depth were evaluated as a function of time with three photo-initiating systems: Irgacure 2959 (Ig2959 320–500 nm), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP 320–500 nm), and ruthenium/sodium persulfate (Ru/SPS 400–500 nm). Results demonstrated that GelAGE precursory solutions mixed with either Ig2959 or LAP remained stable over time while the Ru/SPS system enabled the onset of controllable redox polymerization without irradiation during pre-incubation. Photo-polymerization using the Ru/SPS system was significantly faster ( s) compared to both Ig2959 (70 s) and LAP (50 s). Plus, The Ru/SPS system was capable of polymerizing a thick construct (8.88 ± 0.94 mm), while Ig2959 (1.62 ± 0.49 mm) initiated hydrogels displayed poor penetration depth with LAP (7.38 ± 2.13 mm) in between. These results thus support the use of the visible light based Ru/SPS photo-initiator for constructs requiring rapid gelation and a good curing depth while Ig2959 or LAP can be applied for photo-polymerization of GelAGE materials requiring long-term incubation prior to application if UV is not a concern.
Publisher: Elsevier
Date: 2008
Publisher: Wiley
Date: 10-10-2021
Abstract: While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D‐bioassembly platform is introduced to primarily study fusion of cartilage–cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D‐bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type‐II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D‐model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high‐throughput 3D‐bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis.
Publisher: IOP Publishing
Date: 12-01-2018
Abstract: Bottom-up biofabrication approaches combining micro-tissue fabrication techniques with extrusion-based 3D printing of thermoplastic polymer scaffolds are emerging strategies in tissue engineering. These biofabrication strategies support native self-assembly mechanisms observed in developmental stages of tissue or organoid growth as well as promoting cell-cell interactions and cell differentiation capacity. Few technologies have been developed to automate the precise assembly of micro-tissues or tissue modules into structural scaffolds. We describe an automated 3D bioassembly platform capable of fabricating simple hybrid constructs via a two-step bottom-up bioassembly strategy, as well as complex hybrid hierarchical constructs via a multistep bottom-up bioassembly strategy. The bioassembly system consisted of a fluidic-based singularisation and injection module incorporated into a commercial 3D bioprinter. The singularisation module delivers in idual micro-tissues to an injection module, for insertion into precise locations within a 3D plotted scaffold. To demonstrate applicability for cartilage tissue engineering, human chondrocytes were isolated and micro-tissues of 1 mm diameter were generated utilising a high throughput 96-well plate format. Micro-tissues were singularised with an efficiency of 96.0 ± 5.1%. There was no significant difference in size, shape or viability of micro-tissues before and after automated singularisation and injection. A layer-by-layer approach or aforementioned bottom-up bioassembly strategy was employed to fabricate a bilayered construct by alternatively 3D plotting a thermoplastic (PEGT/PBT) polymer scaffold and inserting pre-differentiated chondrogenic micro-tissues or cell-laden gelatin-based (GelMA) hydrogel micro-spheres, both formed via high-throughput fabrication techniques. No significant difference in viability between the construct assembled utilising the automated bioassembly system and manually assembled construct was observed. Bioassembly of pre-differentiated micro-tissues as well as chondrocyte-laden hydrogel micro-spheres demonstrated the flexibility of the platform while supporting tissue fusion, long-term cell viability, and deposition of cartilage-specific extracellular matrix proteins. This technology provides an automated and scalable pathway for bioassembly of both simple and complex 3D tissue constructs of clinically relevant shape and size, with demonstrated capability to facilitate direct spatial organisation and hierarchical 3D assembly of micro-tissue modules, ranging from biomaterial free cell pellets to cell-laden hydrogel formulations.
Publisher: Wiley
Date: 08-11-2021
Abstract: The principle challenge for engineering viable, cell‐laden hydrogel constructs of clinically‐relevant size, is rapid vascularization, in order to moderate the finite capacity of passive nutrient diffusion. A multiscale vascular approach, with large open channels and bulk microcapillaries may be an admissible approach to accelerate this process, promoting overall pre‐vascularization for long‐term viability of constructs. However, the limited availability of bioinks that possess suitable characteristics that support both fabrication of complex architectures and formation of microcapillaries, remains a barrier to advancement in this space. In this study, gelatin‐norbornene (Gel‐NOR) is investigated as a vascular bioink with tailorable physico‐mechanical properties, which promoted the self‐assembly of human stromal and endothelial cells into microcapillaries, as well as being compatible with extrusion and lithography‐based biofabrication modalities. Gel‐NOR constructs containing self‐assembled microcapillaries are successfully biofabricated with varying physical architecture (fiber diameter, spacing, and orientation). Both channel sizes and cell types affect the overall structural changes of the printed constructs, where cross‐signaling between both human stromal and endothelial cells may be responsible for the reduction in open channel lumen observed over time. Overall, this work highlights an exciting three‐way interplay between bioink formulation, construct design, and cell‐mediated response that can be exploited towards engineering vascular tissues.
Publisher: Oxford University Press (OUP)
Date: 13-08-2021
DOI: 10.1002/SCTM.20-0552
Abstract: The paracrine signaling, immunogenic properties and possible applications of mesenchymal stromal cells (MSCs) for cartilage tissue engineering and regenerative medicine therapies have been investigated through numerous in vitro, animal model and clinical studies. The emerging knowledge largely supports the concept of MSCs as signaling and modulatory cells, exerting their influence through trophic and immune mediation rather than as a cell replacement therapy. The virtues of allogeneic cells as a ready-to-use product with well-defined characteristics of cell surface marker expression, proliferative ability, and differentiation capacity are well established. With clinical applications in mind, a greater focus on allogeneic cell sources is evident, and this review summarizes the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and the role of trophic factors in articular chondrocyte-MSC interactions that offer feasible targets for evaluating MSC activity in vivo within the intra-articular environment. Furthermore, bringing labeling and tracking techniques to the clinical setting, while inherently challenging, will be extremely informative as clinicians and researchers seek to bolster the case for the safety and efficacy of allogeneic MSCs. We therefore review multiple promising approaches for cell tracking and labeling, including both chimerism studies and imaging-based techniques, that have been widely explored in vitro and in animal models. Understanding the distribution and persistence of transplanted MSCs is necessary to fully realize their potential in cartilage regeneration techniques and tissue engineering applications.
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 03-2018
DOI: 10.1302/0301-620X.100B3.BJJ-2017-1135.R1
Abstract: The intra-articular administration of tranexamic acid (TXA) has been shown to be effective in reducing blood loss in unicompartmental knee arthroplasty and anterior cruciate reconstruction. The effects on human articular cartilage, however, remains unknown. Our aim, in this study, was to investigate any detrimental effect of TXA on chondrocytes, and to establish if there was a safe dose for its use in clinical practice. The hypothesis was that TXA would cause a dose-dependent damage to human articular cartilage. The cellular morphology, adhesion, metabolic activity, and viability of human chondrocytes when increasing the concentration (0 mg/ml to 40 mg/ml) and length of exposure to TXA (0 to 12 hours) were analyzed in a 2D model. This was then repeated, excluding cellular adhesion, in a 3D model and confirmed in viable s les of articular cartilage. Increasing concentrations above 20 mg/ml resulted in atypical morphology, reduced cellular adhesion and metabolic activity associated with increased chondrocyte death. However, the cell matrix was not affected by the concentration of TXA or the length of exposure, and offered cellular protection for concentrations below 20 mg/ml. These results show that when in vitro chondrocytes are exposed to higher concentrations of TXA, such as that expected following recommended intra-articular administration, cytotoxicity is observed. This effect is dose-dependent, such that a tissue concentration of 10 mg/ml to 20 mg/ml could be expected to be safe. Cite this article: Bone Joint J 2018 -B:404–12.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.ACTBIO.2018.12.022
Abstract: Decellularisation of tissues, utilising their biochemical cues, poses exciting tissue engineering (TE) opportunities. However, removing DNA from cartilage (dCart) requires harsh treatments due to its dense structure, causing loss of bioactivity and limiting its application as a cartilaginous extra cellular matrix (ECM). In this study, we demonstrate for the first time the successful application of vitreous humor (VH), a highly hydrated tissue closely resembling the glycosaminoglycan (GAG) and collagen composition of cartilage, as an ECM hydrogel to support chondrogenic differentiation. Equine VH was extracted followed by biochemical quantifications, histological examinations, cytotoxicity (human mesenchymal stromal cells, hMSCs and human articular chondrocytes, hACs) and U937 cell proliferation studies. VH was further seeded with hACs or hMSCs and cultured for 3-weeks to study chondrogenesis compared to scaffold-free micro-tissue pellet cultures and collagen-I hydrogels. Viability, metabolic activity, GAG and DNA content, chondrogenic gene expression (aggrecan, collagen I/II mRNA) and mechanical properties were quantified and matrix deposition was visualised using immunohistochemistry (Safranin-O, collagen I/II). VH was successfully extracted, exhibiting negligible amounts of DNA (0.4 ± 0.4 µg/mg dry-weight) and notable preservation of ECM components. VH displayed neither cytotoxic responses nor proliferation of macrophage-like U937 cells, instead enhancing both hMSC and hAC proliferation. Interestingly, encapsulated cells self-assembled the VH-hydrogel into spheroids, resulting in uniform distribution of both GAGs and collagen type II with increased compressive mechanical properties, rendering VH a permissive native ECM source to fabricate cartilaginous hydrogels for potential TE applications. STATEMENT OF SIGNIFICANCE: Fabricating bioactive and cell-instructive cartilage extracellular matrix (ECM) derived biomaterials and hydrogels has over recent years proven to be a challenging task, often limited by poor retention of inherent environmental cues post decellularisation due to the dense and avascular nature of native cartilage. In this study, we present an alternative route to fabricate highly permissive and bioactive ECM hydrogels from vitreous humor (VH) tissue. This paper specifically reports the discovery of optimal VH extraction protocols and cell seeding strategy enabling fabrication of cartilaginous matrix components into a hydrogel support material for promoting chondrogenic differentiation. The work showcases a naturally intact and unmodified hydrogel design that improves cellular responses and may help guide the development of cell instructive and stimuli responsive hybrid biomaterials in a number of TERM applications.
Publisher: Wiley
Date: 23-04-2020
Publisher: Wiley
Date: 20-02-2020
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.BONE.2021.116198
Abstract: Tissue engineering approaches for bone repair have rapidly evolved due to the development of novel biofabrication technologies, providing an opportunity to fabricate anatomically-accurate living implants with precise placement of specific cell types. However, limited availability of biomaterial inks, that can be 3D-printed with high resolution, while providing high structural support and the potential to direct cell differentiation and maturation towards the osteogenic phenotype, remains an ongoing challenge. Aiming towards a multifunctional biomaterial ink with high physical stability and biological functionality, this work describes the development of a nanocomposite biomaterial ink (Mg-PCL) comprising of magnesium hydroxide nanoparticles (Mg) and polycaprolactone (PCL) thermoplastic for 3D printing of strong and bioactive bone regenerative scaffolds. We characterised the Mg nanoparticle system and systematically investigated the cytotoxic and osteogenic effects of Mg supplementation to human mesenchymal stromal cells (hMSCs) 2D-cultures. Next, we prepared Mg-PCL biomaterial ink using a solvent casting method, and studied the effect of Mg over mechanical properties, printability and scaffold degradation. Furthermore, we delivered MSCs within Mg-PCL scaffolds using a gelatin-methacryloyl (GelMA) matrix, and evaluated the effect of Mg over cell viability and osteogenic differentiation. Nanocomposite Mg-PCL could be printed with high fidelity at 20 wt% of Mg content, and generated a mechanical reinforcement between 30%-400% depending on the construct internal geometry. We show that Mg-PCL degrades faster than standard PCL in an accelerated-degradation assay, which has positive implications towards in vivo implant degradation and bone regeneration. Mg-PCL did not affect MSCs viability, but enhanced osteogenic differentiation and bone-specific matrix deposition, as demonstrated by higher ALP/DNA levels and Alizarin Red calcium staining. Finally, we present proof of concept of Mg-PCL being utilised in combination with a bone-specific bioink (Sr-GelMA) in a coordinated-extrusion bioprinting strategy for fabrication of hybrid constructs with high stability and synergistic biological functionality. Mg-PCL further enhanced the osteogenic differentiation of encapsulated MSCs and supported bone ECM deposition within the bioink component of the hybrid construct, evidenced by mineralised nodule formation, osteocalcin (OCN) and collagen type-I (Col I) expression within the bioink filaments. This study demonstrated that magnesium-based nanocomposite bioink material optimised for extrusion-based 3D printing of bone regenerative scaffolds provide enhanced mechanical stability and bone-related bioactivity with promising potential for skeletal tissue regeneration.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2022
DOI: 10.1186/S12951-022-01342-8
Abstract: With the gradual demographic shift toward an aging and obese society, an increasing number of patients are suffering from bone and cartilage injuries. However, conventional therapies are hindered by the defects of materials, failing to adequately stimulate the necessary cellular response to promote sufficient cartilage regeneration, bone remodeling and osseointegration. In recent years, the rapid development of nanomedicine has initiated a revolution in orthopedics, especially in tissue engineering and regenerative medicine, due to their capacity to effectively stimulate cellular responses on a nanoscale with enhanced drug loading efficiency, targeted capability, increased mechanical properties and improved uptake rate, resulting in an improved therapeutic effect. Therefore, a comprehensive review of advancements in nanomedicine for bone and cartilage diseases is timely and beneficial. This review firstly summarized the wide range of existing nanotechnology applications in the medical field. The progressive development of nano delivery systems in nanomedicine, including nanoparticles and biomimetic techniques, which are lacking in the current literature, is further described. More importantly, we also highlighted the research advancements of nanomedicine in bone and cartilage repair using the latest preclinical and clinical ex les, and further discussed the research directions of nano-therapies in future clinical practice. Graphical Abstract
Publisher: Wiley
Date: 17-10-2017
Abstract: Bioprinting can be defined as the art of combining materials and cells to fabricate designed, hierarchical 3D hybrid constructs. Suitable materials, so called bioinks, have to comply with challenging rheological processing demands and rapidly form a stable hydrogel postprinting in a cytocompatible manner. Gelatin is often adopted for this purpose, usually modified with (meth-)acryloyl functionalities for postfabrication curing by free radical photopolymerization, resulting in a hydrogel that is cross-linked via nondegradable polymer chains of uncontrolled length. The application of allylated gelatin (GelAGE) as a thiol-ene clickable bioink for distinct biofabrication applications is reported. Curing of this system occurs via dimerization and yields a network with flexible properties that offer a wider biofabrication window than (meth-)acryloyl chemistry, and without additional nondegradable components. An in-depth analysis of GelAGE synthesis is conducted, and standard UV-initiation is further compared with a recently described visible-light-initiator system for GelAGE hydrogel formation. It is demonstrated that GelAGE may serve as a platform bioink for several biofabrication technologies by fabricating constructs with high shape fidelity via lithography-based (digital light processing) 3D printing and extrusion-based 3D bioprinting, the latter supporting long-term viability postprinting of encapsulated chondrocytes.
Publisher: IOP Publishing
Date: 13-04-2022
Abstract: Bone regeneration of critical-sized bone defects, bone fractures or joint replacements remains a significant clinical challenge. Although there has been rapid advancement in both the fields of bone tissue engineering and additive manufacturing, functional bone implants with rapid vascularization capacity to ensure osseointegration and long-term biological fixation in large bone defects remains limited in clinics. In this study, we developed an in vitro vascularized bone implant by combining cell-laden hydrogels with direct metal printed (DMP) porous titanium alloys (Ti–6Al–4V). A 5 wt% allylated gelatin (GelAGE), was utilized to co-encapsulate human mesenchymal stromal cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) to investigate concurrent osteogenic and vasculogenic performance. DMP macro-porous Ti–6Al–4V scaffolds were subsequently infused/enriched with cell-laden GelAGE to examine the feasibility to deliver cells and engineer vascular-like networks in the hybrid implant. Furthermore, as a proof of concept, a full-scale porous Ti–6Al–4V acetabular cup was impregnated with cell-laden hydrogel to validate the clinical potential of this strategy. The vasculogenic potential was evaluated by examining micro-capillary formation coupled with capillary network maturation and stabilization. Osteogenic differentiation was assessed via alkaline phosphatase activity as well as osteocalcin and osteopontin expression. Our results suggested that GelAGE supported HUVECs spreading and vascular-like network formation, along with osteogenesis of hMSCs. Titanium hybrid constructs with cell-laden hydrogel demonstrated enhanced osteogenesis with similar vasculogenic capability compared to the cell-laden hydrogel alone constructs. The full-scale implant with cell-laden hydrogel coating similarly showed cell distribution and spreading, implying the potential for further clinical application. Our study presents the feasibility of integrating bio-functional hydrogels with porous titanium implants to fabricate a vascularized hybrid construct with both mechanical support and preferable biological functionality (osteogenesis/vasculogenesis), which paves the way for improved strategies to enhance bone regeneration in complex large bone defects achieving long-term bone-implant fixation.
Publisher: AIP Publishing
Date: 04-2021
DOI: 10.1063/5.0035312
Abstract: Detection of early osteoarthritis to stabilize or reverse the damage to articular cartilage would improve patient function, reduce disability, and limit the need for joint replacement. In this study, we investigated nondestructive photon-processing spectral computed tomography (CT) for the quantitative measurement of the glycosaminoglycan (GAG) content compared to destructive histological and biochemical assay techniques in normal and osteoarthritic tissues. Cartilage-bone cores from healthy bovine stifles were incubated in 50% ioxaglate (Hexabrix®) or 100% gadobenate dimeglumine (MultiHance®). A photon-processing spectral CT (MARS) scanner with a CdTe-Medipix3RX detector imaged s les. Calibration phantoms of ioxaglate and gadobenate dimeglumine were used to determine iodine and gadolinium concentrations from photon-processing spectral CT images to correlate with the GAG content measured using a dimethylmethylene blue assay. The zonal distribution of GAG was compared between photon-processing spectral CT images and histological sections. Furthermore, discrimination and quantification of GAG in osteoarthritic human tibial plateau tissue using the same contrast agents were demonstrated. Contrast agent concentrations were inversely related to the GAG content. The GAG concentration increased from 25 μg/ml (85 mg/ml iodine or 43 mg/ml gadolinium) in the superficial layer to 75 μg/ml (65 mg/ml iodine or 37 mg/ml gadolinium) in the deep layer of healthy bovine cartilage. Deep zone articular cartilage could be distinguished from subchondral bone by utilizing the material decomposition technique. Photon-processing spectral CT images correlated with histological sections in healthy and osteoarthritic tissues. Post-imaging material decomposition was able to quantify the GAG content and distribution throughout healthy and osteoarthritic cartilage using Hexabrix® and MultiHance® while differentiating the underlying subchondral bone.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0BM00603C
Abstract: PVA-Tyr hydrogel facilitated covalent incorporation can control release of pristine growth factors while retaining their native bioactivity.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8LC00485D
Abstract: A microplate-based bioreactor was developed to support dual perfusion of parenchymal and barrier tissues for high-throughput microphysiological system (MPS) studies.
Publisher: Portland Press Ltd.
Date: 08-2021
DOI: 10.1042/EBC20200130
Abstract: There remains a critical need to develop new technologies and materials that can meet the demands of treating large bone defects. The advancement of 3-dimensional (3D) printing technologies has allowed the creation of personalized and customized bone grafts, with specific control in both macro- and micro-architecture, and desired mechanical properties. Nevertheless, the biomaterials used for the production of these bone grafts often possess poor biological properties. The incorporation of growth factors (GFs), which are the natural orchestrators of the physiological healing process, into 3D printed bone grafts, represents a promising strategy to achieve the bioactivity required to enhance bone regeneration. In this review, the possible strategies used to incorporate GFs to 3D printed constructs are presented with a specific focus on bone regeneration. In particular, the strengths and limitations of different methods, such as physical and chemical cross-linking, which are currently used to incorporate GFs to the engineered constructs are critically reviewed. Different strategies used to present one or more GFs to achieve simultaneous angiogenesis and vasculogenesis for enhanced bone regeneration are also covered in this review. In addition, the possibility of combining several manufacturing approaches to fabricate hybrid constructs, which better mimic the complexity of biological niches, is presented. Finally, the clinical relevance of these approaches and the future steps that should be taken are discussed.
Publisher: Wiley
Date: 15-01-2020
Abstract: Silk fibroin hydrogels crosslinked through di-tyrosine bonds are clear, elastomeric constructs with immense potential in regenerative medicine applications. In this study, demonstrated is a new visible light-mediated photoredox system for di-tyrosine bond formation in silk fibroin that overcomes major limitations of current conventional enzymatic-based crosslinking. This photomediated system rapidly crosslinks silk fibroin (<1 min), allowing encapsulation of cells at significantly higher cell densities (15 million cells mL
Publisher: Wiley
Date: 25-09-2022
Abstract: Lateral integration and fusion of cartilage tissue interfaces remain significantly challenging and limits success of cartilage tissue engineering (TE) strategies. In this study, self‐assembled vitreous humor (VH) spheroids are fabricated by seeding clinically relevant human articular chondrocytes (hACs) or human mesenchymal stromal cells (hMSCs) in four VH hydrogels with different glycosaminoglycans (GAG) and protein content. Quantitative and qualitative analysis of the VH spheroids revealed that hAC‐VH spheroids are dependent on the initial GAG content of VH hydrogels to achieve successful chondrogenesis. Remarkably, uniform GAG and collagen type II distribution is found in all hMSC‐VH spheroids, independent of the VH donor. HMSC‐VH spheroids are therefore further evaluated for downstream applications by tracking cellular migration, and evaluating neotissue formation at the tissue‐tissue interface of cartilage spheroids 3D‐bioassembled into an in vitro fusion model to asses fusion and integration. hMSC‐VH spheroids enhanced multidirectional cellular migration of both hACs and hMSCs toward the tissue‐tissue interface, and consequently supported dense GAG and collagen type II deposition at the integration region. Ultimately, hMSC‐seeded VH spheroids display successful chondrogenesis and endorse fusion and integration of cartilage tissue interfaces through upregulated cellular migration of clinically relevant cell sources – key elements for clinical translation of cell‐based TE strategies.
Publisher: Wiley
Date: 12-08-2019
Publisher: Springer Singapore
Date: 2018
DOI: 10.1007/978-981-13-0950-2_13
Abstract: Growth factors (GFs) are often a key component in tissue engineering and regenerative medicine approaches. In order to fully exploit the therapeutic potential of GFs, GF delivery vehicles have to meet a number of key design criteria such as providing localized delivery and mimicking the dynamic native GF expression levels and patterns. The use of biomaterials as delivery systems is the most successful strategy for controlled delivery and has been translated into different commercially available systems. However, the risk of side effects remains an issue, which is mainly attributed to insufficient control over the release profile. This book chapter reviews the current strategies, chemistries, materials and delivery vehicles employed to overcome the current limitations associated with GF therapies.
Publisher: IOP Publishing
Date: 11-05-2018
Abstract: Lithography-based three-dimensional (3D) printing technologies allow high spatial resolution that exceeds that of typical extrusion-based bioprinting approaches, allowing to better mimic the complex architecture of biological tissues. Additionally, lithographic printing via digital light processing (DLP) enables fabrication of free-form lattice and patterned structures which cannot be easily produced with other 3D printing approaches. While significant progress has been dedicated to the development of cell-laden bioinks for extrusion-based bioprinting, less attention has been directed towards the development of cyto-compatible bio-resins and their application in lithography-based biofabrication, limiting the advancement of this promising technology. In this study, we developed a new bio-resin based on methacrylated poly(vinyl alcohol) (PVA-MA), gelatin-methacryloyl (Gel-MA) and a transition metal-based visible light photoinitiator. The utilization of a visible light photo-initiating system displaying high molar absorptivity allowed the bioprinting of constructs with high resolution features, in the range of 25-50 μm. Biofunctionalization of the resin with 1 wt% Gel-MA allowed long term survival (>90%) of encapsulated cells up to 21 d, and enabled attachment and spreading of endothelial cells seeded on the printed hydrogels. Cell-laden hydrogel constructs of high resolution with complex and ordered architecture were successfully bioprinted, where the encapsulated cells remained viable, homogenously distributed and functional. Bone and cartilage tissue synthesis was confirmed by encapsulated stem cells, underlining the potential of these DLP-bioprinted hydrogels for tissue engineering and biofabrication. Overall, the PVA-MA/Gel-MA bio-resin is a promising material for biofabrication and provides important cues for the further development of lithography-based bioprinting of complex, free-form living tissue analogues.
Publisher: American Chemical Society (ACS)
Date: 05-12-2018
Publisher: Informa UK Limited
Date: 08-2012
Publisher: Elsevier BV
Date: 05-2020
Publisher: Springer Science and Business Media LLC
Date: 22-12-2011
DOI: 10.1007/S10856-011-4517-Y
Abstract: Magnesium (Mg) alloys are being actively investigated as potential load-bearing orthopaedic implant materials due to their biodegradability in vivo. With Mg biomaterials at an early stage in their development, the screening of alloy compositions for their biodegradation rate, and hence biocompatibility, is reliant on cost-effective in vitro methods. The use of a buffer to control pH during in vitro biodegradation is recognised as critically important as this seeks to mimic pH control as it occurs naturally in vivo. The two different types of in vitro buffer system available are based on either (i) zwitterionic organic compounds or (ii) carbonate buffers within a partial-CO(2) atmosphere. This study investigated the influence of the buffering system itself on the in vitro corrosion of Mg. It was found that the less realistic zwitterion-based buffer did not form the same corrosion layers as the carbonate buffer, and was potentially affecting the behaviour of the hydrated oxide layer that forms on Mg in all aqueous environments. Consequently it was recommended that Mg in vitro experiments use the more biorealistic carbonate buffering system when possible.
Publisher: Springer Science and Business Media LLC
Date: 02-01-2023
Publisher: Wiley
Date: 22-04-2020
Publisher: Informa UK Limited
Date: 13-01-2021
Publisher: Wiley
Date: 18-07-2021
Abstract: 3D printing has emerged as an enabling approach in a variety of different fields. However, the bulk volume of printing systems limits the expansion of their applications. In this study, a portable 3D Digital Light Processing (DLP) printer is built based on a smartphone‐powered projector and a custom‐written smartphone‐operated app. Constructs with detailed surface architectures, porous features, or hollow structures, as well as sophisticated tissue analogs, are successfully printed using this platform, by utilizing commercial resins as well as a range of hydrogel‐based inks, including poly(ethylene glycol)‐diacrylate, gelatin methacryloyl, or allylated gelatin. Moreover, due to the portability of the unique DLP printer, medical implants can be fabricated for point‐of‐care usage, and cell‐laden tissues can be produced in situ, achieving a new milestone for mobile‐health technologies. Additionally, the all‐in‐one printing system described herein enables the integration of the 3D scanning smartphone app to obtain object‐derived 3D digital models for subsequent printing. Along with further developments, this portable, modular, and easy‐to‐use smartphone‐enabled DLP printer is anticipated to secure exciting opportunities for applications in resource‐limited and point‐of‐care settings not only in biomedicine but also for home and educational purposes.
Publisher: American Chemical Society (ACS)
Date: 17-04-2020
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.TIBTECH.2019.04.004
Abstract: Microchannels are simple, perfusable architectural features engineered into biomaterials to promote mass transport of solutes to cells, effective cell seeding and compartmentalisation for tissue engineering applications, control over spatiotemporal distribution of molecules and ligands, and survival, integration, and vascularisation of engineered tissue analogues in vivo. Advances in biofabrication have led to better control over microchannel fabrication in 3D scaffolds, enabling sophisticated designs that drive the development of complex tissue structures. This review addresses the importance of microchannel structures in biomaterial design and regenerative medicine, and discusses their function, fabrication methods, and proposed mechanisms underlying their effects.
Publisher: Elsevier
Date: 2014
Publisher: Elsevier BV
Date: 12-2011
Publisher: Elsevier BV
Date: 12-2019
Publisher: IEEE
Date: 08-2012
Publisher: Elsevier
Date: 2017
Publisher: Wiley
Date: 19-08-2010
DOI: 10.1002/JBM.B.31687
Abstract: A systematic investigation of a series of magnesium-calcium binary alloys is presented to reveal the influence of increasing calcium (Ca) additions on the in vitro degradation of magnesium (Mg). Because of its prevalence in structural tissues, Ca is among the most biologically viable additions to orthopedic-intended Mg-based biomaterials. Hence, a fundamental electrochemical study of Ca additions to Mg biomaterials is essential to its continued role as an alloying addition. In this work, in vitro degradation conditions closer to the physiological environment were implemented through the addition of proteins to simulated body fluid and maintenance of a constant pH, with tests conducted using Hanks solution, minimum essential medium (MEM), and MEM containing fetal bovine serum. Alloying with Ca leads to the formation of Mg2Ca intermetallic particles that result in systematically enhanced dissolution kinetics. This observation is rationalized via microelectrochemical tests upon the Mg2Ca intermetallic in isolation, which reveals rapid anodic kinetics. Hence, the extent of Mg-Ca alloy dissolution can be modified depending on the amount of Mg2Ca present, suggesting that Ca can be deployed as a functional addition capable of not only enhancing biodissolution of the alloy, but being able to do this in a systematic, controllable manner depending on its volume fraction. In addition, up to a 3-fold reduction in the corrosion rate is observed with corrosion testing in an albumin-containing medium when compared to Hanks solution, the results highlighting that the use of a physiologically "correct" medium is essential for the in vitro screening of Mg-based alloys suitable for orthopaedic applications.
Publisher: IOP Publishing
Date: 26-03-2014
No related organisations have been discovered for Tim Woodfield.
Start Date: 07-2021
End Date: 06-2024
Amount: $472,248.00
Funder: Australian Research Council
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