Biology subjects

Dawson, J. I.

Publications and source records attributed to Dawson, J. I..

7 recordsLinked to original sources

bioRxiv2026

Decoupled ionic and particulate clearance pathways determine the in vivo fate of a synthetic nanoclay-BMP-2 biomaterial during ectopic bone induction.

Nanoclay-based biomaterials offer promise for localised growth factor presentation, yet their in vivo degradation, clearance, and systemic fate remain poorly defined. Here, we investigate the fate of a synthetic nanoclay-BMP-2 gel during ectopic bone induction using a combination of in vivo imaging, histology, and component-resolved elemental analysis. Fluorescent tracking confirmed prolonged localisation of BMP-2 within the nanoclay gel and robust bone induction despite negligible growth-factor release. Inductively coupled plasma mass spectrometry (ICP-MS) revealed divergent clearance kinetics for lithium and silicon, structurally distinct components of the clay crystalline lattice, indicating decoupled ionic and particulate degradation pathways. Early clearance was dominated by cell-mediated fragmentation and the transport of clay particulates, while later stages involved preferential lithium release associated with local clay dissolution as well as integration within newly formed bone. Systemic biodistribution analysis demonstrated rapid, transient lithium release into circulation with renal clearance, contrasted with initial hepatic and then later-phase renal handling of silicon species. Together, these findings define a multiphasic in vivo clearance model for nanoclay biomaterials consistent with progressive remodelling, localised BMP-2 activity and, importantly, safe systemic handling. This work provides mechanistic insight into the activity and clearance of nanoclay-based regenerative therapies and establishes the importance of component-resolved tracking for evaluating the biodistribution of degradable inorganic biomaterials.

bioengineering↗

bioRxiv2024

Bioactive coatings on 3D printed scaffolds for bone regeneration: Use of Laponite(R) to deliver BMP-2 in an ovine femoral condyle defect model

Biomaterial-based approaches for bone regeneration seek to explore alternative strategies to repair non-healing fractures and critical-sized bone defects. Fracture non-union occurs due to a number of factors resulting in the formation of bone defects. Rigorous evaluation of the biomaterials in relevant models and assessment of their potential to translate towards clinical use is vital. Large animal experimentation can be used to model fracture non-union while scaling-up materials for clinical use. Growth factors modulate cell phenotype, behaviour and initiate signalling pathways leading to changes in matrix deposition and tissue formation. Bone morphogenetic protein-2 (BMP-2) is a potent osteogenic growth factor, with a rapid clearance time in vivo necessitating clinical use at a high dose, with potential deleterious side-effects. The current studies have examined the potential for Laponite(R) nanoclay coated poly(caprolactone) trimethacrylate (PCL-TMA900) scaffolds to bind BMP-2 for enhanced osteoinduction in a large animal critical-sized bone defect. An ovine femoral condyle defect model confirmed PCL-TMA900 scaffolds coated with Laponite(R)/BMP-2 produced significant bone formation compared to the uncoated PCL-TMA 900 scaffold in vivo, assessed by micro-computed tomography ({micro}CT) and histology. This indicated the ability of Laponite(R) to deliver the bioactive BMP-2 on the PCL-TMA900 scaffold. Bone formed around the Laponite(R)/BMP-2 coated PCL-TMA900 scaffold, with no erroneous bone formation observed away from the scaffold material confirming localisation of BMP-2 delivery. The current studies demonstrate the ability of a nanoclay to localise and deliver bioactive BMP-2 within a tailored octet-truss scaffold for efficacious bone defect repair in a large animal model with significant implications for translation to the clinic.

bioengineering↗

bioRxiv2023

Bioactive coatings on 3D printed polycaprolactone scaffolds for bone regeneration: a novel murine femur defect model for examination of the biomaterial capacity for repair.

Bone tissue engineering is a rapidly advancing field that seeks to develop efficacious approaches for treating non-healing fractures and large bone defects. Healing complications arise due to trauma, disease, infection, aseptic loosening of orthopaedic implants or iatrogenic causes. An ideal biodegradable scaffold would induce and support bone formation until the bone matrix is sufficiently stable to facilitate healing. The current study has examined bone augmentation, using functionalised coated scaffolds, with the hypothesised potential to induce skeletal cell differentiation for the repair of critical-sized bone defects. However, challenges in clinical translation arise from the alterations in cellular microenvironment that are present in the translation from in vitro to in vivo with the application of animal models of progressively increasing size and complexity of the implantation site. 3D printed, porous poly(caprolactone) trimethacrylate (denoted PCL-TMA900) scaffolds were applied within a murine femur defect, stabilised by a polyimide intramedullary pin, to assess the efficacy of select coatings in inducing bone formation. The PCL-TMA900 scaffolds were coated with i) elastin-like polypeptide (ELP), ii) poly(ethyl acrylate)/fibronectin/bone morphogenetic protein-2 (PEA/FN/BMP-2), iii) both ELP and PEA/FN/BMP-2 concurrently, or iv) Laponite nanoclay binding BMP-2, as bioactive coatings. The murine femur defect model was refined to assess the coated PCL-TMA900 scaffolds in an osseous defect, with sequential microcomputed tomography ({micro}CT) and histological analysis of the new bone tissue. Overall, PCL-TMA900 was found to be an optimal robust, biocompatible, 3D printable scaffold material. All PCL-TMA900 scaffolds, uncoated and coated, showed integration with the femur. The PCL-TMA900 scaffold coated with the nanoclay material Laponite and BMP-2 induced consistent, significant bone formation compared to the uncoated PCL-TMA900 scaffold. Bone formation was observed within the pores of the Laponite/BMP-2 coated scaffold. Critically, no heterotopic bone formation was observed as the BMP-2 was retained around the scaffold and not released into the tissues, producing bone around the scaffold in the desired shape and volume, compared to bone formation observed with the positive control (collagen sponge/BMP-2 construct). In comparison, the ELP coated and PEA/FN/BMP-2 scaffolds did not demonstrate significant or consistent bone formation compared to uncoated PCL-TMA900 control scaffolds. In summary, nanoclay Laponite/BMP-2 coated PCL-TMA900 scaffolds offer a biodegradable, osteogenic construct for bone augmentation with potential for development into a large scale polymer scaffold for translation to the clinic.

bioengineering↗

bioRxiv2023

Bioactive coatings on 3D printed scaffolds for bone regeneration: Use of Laponite™ to deliver BMP-2 for bone tissue engineering - progression through in vitro, chorioallantoic membrane assay and murine subcutaneous model validation.

Fracture non-union occurs as a consequence of various factors, leading to the development of potentially substantial bone defects. Biomaterial-based approaches for bone regeneration aim to explore alternative strategies to repair non-healing fractures and critical-sized bone defects. Thus, rigorous assessment of the ability to translate biomaterials towards clinical use is vital. Growth factors induce an effect on cells to change their phenotype, behaviour and initiate signalling pathways, leading to an effect on matrix deposition and tissue formation. Bone morphogenetic protein-2 (BMP-2) is a potent osteogenic growth factor, with a rapid clearance time in vivo necessitating clinical use of high doses, with potential deleterious side-effects. This work explored the potential for Laponite nanoclay coating of poly(caprolactone) trimethacrylate (PCL-TMA900) scaffolds to bind BMP-2 for enhanced osteoinduction. In vitro experiments confirmed the cytocompatibility of the PCL-TMA900 scaffolds and effective osteogenic differentiation of C2C12 myoblast cells in response to the Laponite/BMP-2 coating. The chorioallantoic membrane (CAM) assay verified PCL-TMA900 scaffold material biocompatibility and ability to support angiogenesis. A murine subcutaneous implantation model assessed heterotopic bone formation in response to the Laponite/BMP-2 coating, when used immediately post-coating and after 24 hours of room temperature storage, to evaluate a delayed use manner. The Laponite/BMP-2 coated PCL-TMA900 scaffolds implanted showed consistent, significant bone formation over the study period compared to the uncoated PCL-TMA 900 scaffold and BMP-2 only coated control scaffolds in vivo, indicating the ability of Laponite to bind the BMP-2 to the PCL-TMA900 scaffold. Bone formed peripherally around the Laponite/BMP-2 coated scaffold, with no aberrant bone formation observed. The Laponite/BMP-2 coating was found to retain its bioactivity after storage for 24 hours prior to use in vivo, however this was not to the same volume or reliability of bone formation as when used immediately post-coating. To take these studies forward, the Laponite/BMP-2 coating warrants examination in a critical-sized bone defect model to assess efficacy in an osseous site.

bioengineering↗

bioRxiv2023

Human bone tissue-derived ECM hydrogels: Controlling physicochemical, biochemical, and biological properties through processing parameters

Decellularized tissues offer significant potential as biological materials for tissue regeneration due to their ability to preserve the complex compositions and architecture of the native extracellular matrix (ECM). While the use of decellularized ECM hydrogels from bovine and porcine bone tissues has been extensively studied, the evaluation and derivation of decellularized matrices from human bone tissue remain largely unexplored. The objective of this study was to investigate how the physiochemical and biological properties of ECM hydrogels derived from human bone ECM could be controlled by manipulating bone powder size (45-250 m, 250-1000 m, and 1000-2000 m) and ECM composition through modulation of digestion time (3, 5, and 7 days). The current studies demonstrate that a reduction in material bone powder size and an increase in ECM digestion time resulted in enhanced protein concentrations in the ECM hydrogels, accompanied by the presence of a diverse array of proteins. Furthermore, these adjustments in the physicochemical properties generated improved gelation strength of the hydrogels. The evaluation of human bone marrow-derived stromal cells (HBMSCs) cultured on ECM hydrogels derived from 45-250 m bone powder, treated for 7 days, demonstrated enhanced osteogenic differentiation compared to hydrogels derived from both larger bone powders and collagen gels. In conclusion, this study highlights the significant promise of human bone ECM hydrogels as biologically active materials for bone regeneration. The ability to manipulate digestion time and bone powder size enables the generation of hydrogels with enhanced release of ECM proteins and appropriate gelation and rheological properties, offering new opportunities for application in bone tissue engineering.

bioengineering↗

bioRxiv2023

Biofabrication of nanocomposite-based scaffolds containing human bone extracellular matrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair but can fail to provide a long-term clinical resolution, emphasising the need for a functional biomimetic tissue engineering alternative. An attractive sustainable opportunity for tissue regeneration would be the application of human bone waste tissue for the synthesis of a material ink for 3D bioprinting of skeletal tissue. The use of human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate micro-environment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. Extrusion-based deposition was mediated by the blending of human bone-ECM (B) with nanoclay (L, Laponite(R)) and alginate (A) polymer, to engineer a novel material ink (LAB). The inclusion of nanofiller and polymeric material increased the rheological, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularisation following implantation in an ex vivo chick chorioallantoic membrane (CAM) model. Addition of bone morphogenetic protein-2 (BMP-2) with HBMSCs further enhanced vascularisation together with mineralisation after only 7 days. The current study demonstrates the synergistic combination of nanoclay with biomimetic materials, (alginate and bone-ECM) to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalised skeletal tissue repair. Graphical AbstractEngineering nanoclay-based bone ECM novel bioink for bone regeneration. Human bone trabecular tissue was demineralised, decellularised and blended with nanoclay (Laponite(R)) and alginate after digestion. The resulting ink was investigated for printability following rheological and filament fusion investigation. The microstructural arrangement of the blends was examined together with viability and functionality of bioprinted HBMSCs. Finally, the ability of the novel blend to support drug release ex vivo in a CAM model was determined confirming the potential of the bone ECM ink to support bone formation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/536074v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@b9dc13org.highwire.dtl.DTLVardef@1f6f0dorg.highwire.dtl.DTLVardef@1b3c098org.highwire.dtl.DTLVardef@295192_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2019

Injectable nanoclay gels for angiogenesis

The retention and sustained activity of therapeutic proteins at delivery sites are goals of regenerative medicine. Vascular endothelial growth factor (VEGF) has significant potential in promoting the growth and regeneration of blood vessels but is intrinsically labile. This is exacerbated by the inflammatory microenvironments at sites requiring regeneration. For VEGF to be efficacious it may require a carrier that stabilises it, protects it from degradation and retains it at a site of interest. In this study we tested the hypothesis that injectable nanoclay gels composed of Laponite XLG can stabilise VEGF and retain it in active form for therapeutic delivery. To achieve this, VEGF was incorporated in Laponite gels and its activity tested at a range of concentrations using in vivo cell culture tubulogenesis assays and in vivo angiogenesis assays. We found that VEGF-Laponite gels enhanced tubulogenesis in a dose-dependent manner in vivo. When administered subcutaneously in vivo Laponite was retained at an injection site for up to a period of three weeks and promoted a 4-fold increase in blood vessel formation compared with alginate or vehicle controls as confirmed by CD31 staining. Notably, in contrast to alginate, Laponite gels did not release VEGF, indicating a strong interaction between the growth factor and the nanoclay, and suggesting that Laponite enhancement of VEGF efficacy is due to its retention at an implantation site over a prolonged period. Our approach provides a robust method for delivery of bioactive recombinant VEGF without the necessity for complex hydrogel or protein engineering.

bioengineering↗