Three Dimensional Porous Binary Composites of Collagen, Elastin and Fibrin Proteins Orchestrate Adipose Tissue Regeneration.

The development of an optimal healthcare biomaterial for targeted tissue regeneration poses a significant challenge. Our current objective is to advance the development of a specialised biomaterial that can effectively facilitate the regeneration of adipose tissue. In prior studies, the assessment of collagen, elastin, and fibrin unary scaffolds has been conducted. However, it is important to note that native adipose tissue is comprised of a diverse array of extracellular matrix (ECM) constituents. To mimic this behaviour we fabricated binary compositions of collagen, elastin, and fibrin in a 1:1 ratio, resulting in the formation of Col/Ela, Col/Fib, and Ela/Fib composites through a customised fabrication procedure. The physical properties of these scaffolds were comprehensively analysed using a range of material characterisation techniques. Additionally, the biological properties of the scaffolds were investigated by examining the survival, proliferation, and phenotype of adipose-derived stem cells. Subsequently, the aforementioned binary scaffolds were introduced into a live rodent model for a duration of 28 days. Following this period, the explants were subjected to analysis through X-ray microtomography, histology, and immunohistochemistry in order to evaluate their immunocompatibility, integration, and adipogenesis. The findings of the study demonstrated that the utilisation of binary combinations of Col/Ela, Col/Fib, and Ela/Fib had a discernible impact on the physical and biological characteristics of the scaffolds. Nevertheless, Ela/Fib exhibited characteristics that made it a suitable candidate for adipogenesis due to its notable upregulation of caveolin-1 expression in both acellular and cellular cohorts. The combination of two natural polymers in this cell-material interaction has significantly enhanced our comprehension of adipogenesis. This article is protected by copyright. All rights reserved.

Inclusion of calcium phosphate does not further improve in vitro and in vivo osteogenesis in a novel, highly biocompatible, mechanically stable and 3D printable polymer.

At a time of unpredictable challenges for health, one trend is certain: there is an exceedingly high demand for functional implants, particularly bone grafts. This has encouraged the emergence of bone tissue engineering substitutes as an alternative method to conventional bone grafts. However, the current approaches in the field face several limitations that have prevented the ultimate translation into clinical settings. As a result, many attempts have been made to fabricate synthetic bone implants that can offer suitable biological and mechanical properties.Light curable methacrylate-based polymers have ideal properties for bone repair. These materials are also suitable for 3D printing which can be applicable for restoration of both function and aesthetics. The main objective of this research was to investigate the role of calcium phosphate (CaP) incorporation in a mechanically stable, biologically functional and 3D printable polymer for the reconstruction of complex craniofacial defects. The experimental work initially involved the synthesis of (((((((((((3R,3aR,6S,6aR)- hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1- 48 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(3,3,5-trimethylcyclohexane-5,1- 49 diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane-2,1-diyl) bis(2-methylacrylate) referred to as CSMA and fabrication of composite discs via a Digital Light Printing (DLP) method. The flow behaviour of the polymer as a function of CaP addition, surface remineralisation potential, in vitro cell culture, using MC3T3 and Adipose-Derived Mesenchymal Stem Cells (ADSCs) and ex ovo angiogenic response was assessed. Finally, in vivo studies were carried out to investigate neo-bone formation at 4- and 8-weeks post-implantation. Quantitative micro-CT and histological evaluation did not show a higher rate of bone formation in CaP filled CSMA composites compared to CSMA itself. Therefore, such polymeric systems hold promising features by allowing more flexibility in designing a 3D printed scaffold targeted at the reconstruction of maxillofacial defects.

Cell morphology as a design parameter in the bioengineering of cell-biomaterial surface interactions.

Control of cell-surface interaction is necessary for biomaterial applications such as cell sheets, intelligent cell culture surfaces, or functional coatings. In this paper, we propose the emergent property of cell morphology as a design parameter in the bioengineering of cell-biomaterial surface interactions. Cell morphology measured through various parameters can indicate ideal candidates for these various applications thus reducing the time taken for the screening and development process. The hypothesis of this study is that there is an optimal cell morphology range for enhanced cell proliferation and migration on the surface of biomaterials. To test the hypothesis, primary porcine dermal fibroblasts (PDF, 3 biological replicates) were cultured on ten different surfaces comprising components of the natural extracellular matrix of tissues. Results suggested an optimal morphology with a cell aspect ratio (CAR) between 0.2 and 0.4 for both increased cell proliferation and migration. If the CAR was below 0.2 (very elongated cell), cell proliferation was increased whilst migration was reduced. A CAR of 0.4+ (rounded cell) favoured cell migration over proliferation. The screening process, when it comes to biomaterials is a long, repetitive, arduous but necessary event. This study highlights the beneficial use of testing the cell morphology on prospective prototypes, eliminating those that do not support an optimal cell shape. We believe that the research presented in this paper is important as we can help address this screening inefficiency through the use of the emergent property of cell morphology. Future work involves automating CAR quantification for high throughput screening of prototypes.

Varying 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) level improves polymerisation kinetics and flexural strength in self-adhesive, remineralising composites.

OBJECTIVES: To assess the influence of systematically varying concentrations of 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) versus 3% 4-META on the polymerisation kinetics and shrinkage, biaxial flexural strength (BFS) and modulus of remineralising composites. METHODS: Composites were prepared by adding poly(propylene glycol) dimethacrylate (24 wt%), camphorquinone (1 wt%) and MDP (0%, 5%, 10%, 15% and 20 wt%) or 4-META (3%) to urethane dimethacrylate. These were mixed with glass fillers containing 8 wt% monocalcium phosphate and 4 wt% polylysine (powder-liquid ratio of 3:1). Continuous spectral changes, following 20 s light exposure (37 °C), were assessed with an ATR-FTIR to monitor polymerisation kinetics (n = 3). Final extrapolated conversions (DC,max) were employed to calculate polymerisation shrinkage. BFS and modulus of 24-h dry stored disc specimens (10 × 1 mm; n = 10) were determined using a ball-on-ring jig setup. RESULTS: Maximum rate of polymerisation and DC,max increased linearly from 2.5 to 3.5% s-1 and 67 to 83%, respectively, upon increasing MDP from 0 to 20 wt%. Values with 3% 4-META were 2.6% s-1 and 78%. Shrinkage was 3.8 ± 0.3% for all formulations. Raising 4-META or MDP from 0 to 3 versus 5%, respectively, increased strength from 106 to 145 versus 136 MPa. A decreasing trend with higher MDP concentrations was noted. Elastic modulus showed no specific trend upon MDP increase. SIGNIFICANCE: Whilst final conversion levels were enhanced by 3% 4-META or >5% MDP, trends did not correlate with strength. Peak strengths with 3% 4-META or 5% MDP may therefore be due to acidic monomers providing linkage between the hydrophilic, non-silane treated particles and the polymer matrix.

Mussel Inspired Chemistry and Bacteria Derived Polymers for Oral Mucosal Adhesion and Drug Delivery.

Ulceration of the oral mucosa is common, can arise at any age and as a consequence of the pain lessens enjoyment and quality of life. Current treatment options often involve the use of topical corticosteroids with poor drug delivery systems and inadequate contact time. In order to achieve local controlled delivery to the lesion with optimal adhesion, we utilized a simple polydopamine chemistry technique inspired by mussels to replicate their adhesive functionality. This was coupled with production of a group of naturally produced polymers, known as polyhydroxyalkanoates (PHA) as the delivery system. Initial work focused on the synthesis of PHA using Pseudomonas mendocina CH50; once synthesized and extracted from the bacteria, the PHAs were solvent processed into films. Polydopamine coating was subsequently achieved by immersing the solvent cast film in a polymerized dopamine solution. Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy confirmed functionalization of the PHA films via the presence of amine groups. Further characterization of the samples was carried out via surface energy measurements and Scanning Electron Microscopy (SEM) micrographs for surface topography. An adhesion test via reverse compression testing directly assessed adhesive properties and revealed an increase in polydopamine coated samples. To further identify the effect of surface coating, LIVE/DEAD imaging and Alamar Blue metabolic activity evaluated attachment and proliferation of fibroblasts on the biofilm surfaces, with higher cell growth in favor of the coated samples. Finally, in vivo biocompatibility was investigated in a rat model where the polydopamine coated PHA showed less inflammatory response over time compared to uncoated samples with sign of neovascularization. In conclusion, this simple mussel inspired polydopamine chemistry introduces a step change in bio-surface functionalization and holds great promise for the treatment of oral conditions.

Pro-angiogenic and osteogenic composite scaffolds of fibrin, alginate and calcium phosphate for bone tissue engineering.

Due to the limitations of bone autografts, we aimed to develop new composite biomaterials with pro-angiogenic and osteogenic properties to be used as scaffolds in bone tissue engineering applications. We used a porous, cross-linked and slowly biodegradable fibrin/alginate scaffold originally developed in our laboratory for wound healing, throughout which deposits of calcium phosphate (CaP) were evenly incorporated using an established biomimetic method. Material characterisation revealed the porous nature and confirmed the deposition of CaP precursor phases throughout the scaffolds. MC3T3-E1 cells adhered to the scaffolds, proliferated, migrated and differentiated down the osteogenic pathway during the culture period. Chick chorioallantoic membrane (CAM) assay results showed that the scaffolds were pro-angiogenic and biocompatible. The work presented here gave useful insights into the potential of these pro-angiogenic and osteogenic scaffolds for bone tissue engineering and merits further research in a pre-clinical model prior to its clinical translation.

Enhancing Distraction Osteogenesis With Carbon Fiber Reinforced Polyether Ether Ketone Bone Pins and a Three-Dimensional Printed Transfer Device to Permit Artifact-Free Three-Dimensional Magnetic Resonance Imaging.

OBJECTIVES: To: (1) design an artifact-free 3D-printed MR-safe temporary transfer device, (2) engineer bone-pins from carbon fiber reinforced polyether ether ketone (CFR-PEEK), (3) evaluate the imaging artifacts of CFR-PEEK, and (4) confirm the osteointegration potential of CFR-PEEK, thus enhancing 3D-planning of bony advancements in hemifacial microsomia using sequential magnetic resonance imaging (MRI). STUDY DESIGN: Engineered CRF-PEEK bone pins and a 3D printed ex-fix device were implanted into a sheep head and imaged with MRI and computed tomography . The osseointegration and bony compatibility potential of CFR-PEEK was assessed with scanning electron microscopy images of MC3T3 preosteoblast cells on the surface of the material. RESULTS: The CFR-PEEK pins resulted in a signal void equivalent to the dimension of the pin, with no adjacent areas of MR-signal loss or computed tomography artifact. MCT3 cells adhered and proliferated on the surface of the discs by forming a monolayer of cells, confirming compatibility and osseointegration potential. CONCLUSION: A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation.

Comparative study of photoinitiators for the synthesis and 3D printing of a light-curable, degradable polymer for custom-fit hard tissue implants.

Three-dimensional (3D) printing enhances the production of on-demand fabrication of patient-specific devices, as well as anatomically fitting implants with high complexity in a cost-effective manner. Additive systems that employ vat photopolymerisation such as stereolithography (SLA) and digital light projection are used widely in the field of biomedical science and engineering. However, additive manufacturing methods can be limited by the types of materials that can be used. In this study, we present an isosorbide-based formulation for a polymer resin yielding a range of elastic moduli between 1.7 and 3 GN mm-2 dependent on the photoinitiator system used as well as the amount of calcium phosphate filler added. The monomer was prepared and enhanced for 3D-printing using an SLA technique that delivered stable and optimized 3D-printed models. The resin discussed could potentially be used following major surgery for the correction of congenital defects, the removal of oral tumours and the reconstruction of the head and neck region. The surgeon is usually limited with devices available to restore both function and appearance and with the ever-increasing demand for low-priced and efficient facial implants, there is an urgent need to advance new manufacturing approaches and implants with a higher osseointegration performance.

Synthesis, Characterization, and 3D Printing of an Isosorbide-Based, Light-Curable, Degradable Polymer for Potential Application in Maxillofacial Reconstruction.

Although emergence of bone tissue engineering techniques has revolutionized the field of maxillofacial reconstruction, the successful translation of such products, especially concerning larger sized defects, still remains a significant challenge. Light-curable methacrylate-based polymers have ideal properties for bone repair. These materials are also suitable for 3D printing which can be applicable for restoration of both function and aesthetics. The main objective of this research was to synthesize a mechanically stable and biologically functional polymer for reconstruction of complex craniofacial defects. The experimental work initially involved synthesis of (((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1-diyl)bis((4-methyl-3-oxopent-4-en-1-yl)carbamate), CSMA-1, and ((((((((((((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(methylene))bis(3,3,5-trimethylcyclohexane-5,1-diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane-2,1-diyl)bis(2-methylacrylate), CSMA-2; nuclear magnetic resonance analysis confirmed formation of the monomers, and composite samples were fabricated respectively by exposing 11 mm diameter discs to blue light. Modulus of elasticity was determined using a biaxial flexural test and the values were found to be between 1 and 3 GPa in CSMA-1, CSMA-2, and their composites. In vitro cell culture, using human bone marrow-derived mesenchymal stem cells, confirmed nontoxicity of the samples and finally 3D printing allowed direct photo-polymerization and setting of the bio ink into a 3D construct.

Three-dimensional Printing in Maxillofacial Surgery: Hype versus Reality.

Three-dimensional printing technology is getting more attention recently, especially in the craniofacial region. This is a review of literature enlightening the materials that have been used to date and the application of such technology within the scope of maxillofacial surgery.