Project description:Bone is remodeled through a dynamic process facilitated by biophysical cues that support cellular signaling. In healthy bone, signaling pathways are regulated by cells and the extracellular matrix and transmitted via electrical synapses. To this end, combining electrical stimulation (ES) with conductive scaffolding is a promising approach for repairing damaged bone tissue. Therefore, "smart" biomaterials that can provide multifunctionality and facilitate the transfer of electrical cues directly to cells have become increasingly more studied in bone tissue engineering. Herein, 3D-printed electrically conductive composite scaffolds consisting of demineralized bone matrix (DBM) and polycaprolactone (PCL), in combination with ES, for bone regeneration were evaluated for the first time. The conductive composite scaffolds were fabricated and characterized by evaluating mechanical, surface, and electrical properties. The DBM/PCL composites exhibited a higher compressive modulus (107.2 MPa) than that of pristine PCL (62.02 MPa), as well as improved surface properties (i.e., roughness). Scaffold electrical properties were also tuned, with sheet resistance values as low as 4.77 × 105 Ω/sq for our experimental coating of the highest dilution (i.e., 20%). Furthermore, the biocompatibility and osteogenic potential of the conductive composite scaffolds were tested using human mesenchymal stromal cells (hMSCs) both with and without exogenous ES (100 mV/mm for 5 min/day four times/week). In conjunction with ES, the osteogenic differentiation of hMSCs grown on conductive DBM/PCL composite scaffolds was significantly enhanced when compared to those cultured on PCL-only and nonconductive DBM/PCL control scaffolds, as determined through xylenol orange mineral staining and osteogenic protein analysis. Overall, these promising results suggest the potential of this approach for the development of biomimetic hybrid scaffolds for bone tissue engineering applications.
Project description:Electrostimulation and electroactive scaffolds can positively influence and guide cellular behaviour and thus has been garnering interest as a key tissue engineering strategy. The development of conducting polymers such as polyaniline enables the fabrication of conductive polymeric composite scaffolds. In this study, we report on the initial development of a polycaprolactone scaffold incorporating different weight loadings of a polyaniline microparticle filler. The scaffolds are fabricated using screw-assisted extrusion-based 3D printing and are characterised for their morphological, mechanical, conductivity, and preliminary biological properties. The conductivity of the polycaprolactone scaffolds increases with the inclusion of polyaniline. The in vitro cytocompatibility of the scaffolds was assessed using human adipose-derived stem cells to determine cell viability and proliferation up to 21 days. A cytotoxicity threshold was reached at 1% wt. polyaniline loading. Scaffolds with 0.1% wt. polyaniline showed suitable compressive strength (6.45 ± 0.16 MPa) and conductivity (2.46 ± 0.65 × 10-4 S/cm) for bone tissue engineering applications and demonstrated the highest cell viability at day 1 (88%) with cytocompatibility for up to 21 days in cell culture.
Project description:Cryogels, known for their biocompatibility and porous structure, lack mechanical strength, while 3D-printed scaffolds have excellent mechanical properties but limited porosity resolution. By combining a 3D-printed plastic gyroid lattice scaffold with a chitosan-gelatin cryogel scaffold, a scaffold can be created that balances the advantages of both fabrication methods. This study compared the pore diameter, swelling potential, mechanical characteristics, and cellular infiltration capability of combined scaffolds and control cryogels. The incorporation of the 3D-printed lattice demonstrated patient-specific geometry capabilities and significantly improved mechanical strength compared to the control cryogel. The combined scaffolds exhibited similar porosity and relative swelling ratio to the control cryogels. However, they had reduced elasticity, reduced absolute swelling capacity, and are potentially cytotoxic, which may affect their performance. This paper presents a novel approach to combine two scaffold types to retain the advantages of each scaffold type while mitigating their shortcomings.
Project description:The rapid growth and disruptive potentials of three-dimensional (3D) printing demand further research for addressing fundamental fabrication concepts and enabling engineers to realize the capabilities of 3D printing technologies. There is a trend to use these capabilities to develop materials that derive some of their properties via their structural organization rather than their intrinsic constituents, sometimes referred to as mechanical metamaterials. Such materials show qualitatively different mechanical behaviors despite using the same material composition, such as ultra-lightweight, super-elastic, and auxetic structures. In this work, we review current advancements in the design and fabrication of multi-scale advanced structures with properties heretofore unseen in well-established materials. We classify the fabrication methods as conventional methods, additive manufacturing techniques, and 4D printing. Following a comprehensive comparison of different fabrication methods, we suggest some guidelines on the selection of fabrication parameters to construct meta-biomaterials for tissue engineering. The parameters include multi-material capacity, fabrication resolution, prototyping speed, and biological compatibility.
Project description:Hydrogel-based bio-inks have been extensively used for developing three-dimensional (3D) printed biomaterials for biomedical applications. However, poor mechanical performance and the inability to conduct electricity limit their application as wearable sensors. In this work, we formulate a novel, 3D printable electro-conductive hydrogel consisting of silicate nanosheets (Laponite), graphene oxide, and alginate. The result generated a stretchable, soft, but durable electro-conductive material suitable for utilization as a novel electro-conductive bio-ink for the extrusion printing of different biomedical platforms, including flexible electronics, tissue engineering, and drug delivery. A series of tensile tests were performed on the material, indicating excellent stability under significant stretching and bending without any conductive or mechanical failures. Rheological characterization revealed that the addition of Laponite enhanced the hydrogel's mechanical properties, including stiffness, shear-thinning, and stretchability. We also illustrate the reproducibility and flexibility of our fabrication process by extrusion printing various patterns with different fiber diameters. Developing an electro-conductive bio-ink with favorable mechanical and electrical properties offers a new platform for advanced tissue engineering.
Project description:3D printing involves the development of inks that exhibit the requisite properties for both printing and the intended application. In bioprinting, these inks are often hydrogels with controlled rheological properties that can be stabilized after deposition. Here, an alternate approach is developed where the ink is composed exclusively of jammed microgels, which are designed to incorporate a range of properties through microgel design (e.g., composition, size) and through the mixing of microgels. The jammed microgel inks are shear-thinning to permit flow and rapidly recover upon deposition, including on surfaces or when deposited in 3D within hydrogel supports, and can be further stabilized with secondary cross-linking. This platform allows the use of microgels engineered from various materials (e.g., thiol-ene cross-linked hyaluronic acid (HA), photo-cross-linked poly(ethylene glycol), thermo-sensitive agarose) and that incorporate cells, where the jamming process and printing do not decrease cell viability. The versatility of this particle-based approach opens up numerous potential biomedical applications through the printing of a more diverse set of inks.
Project description:The prevalence of large bone defects is still a major problem in surgical clinics. It is, thus, not a surprise that bone-related research, especially in the field of bone tissue engineering, is a major issue in medical research. Researchers worldwide are searching for the missing link in engineering bone graft materials that mimic bones, and foster osteogenesis and bone remodeling. One approach is the combination of additive manufacturing technology with smart and additionally electrically active biomaterials. In this study, we performed a three-dimensional (3D) printing process to fabricate piezoelectric, porous barium titanate (BaTiO3) and hydroxyapatite (HA) composite scaffolds. The printed scaffolds indicate good cytocompatibility and cell attachment as well as bone mimicking piezoelectric properties with a piezoelectric constant of 3 pC/N. This work represents a promising first approach to creating an implant material with improved bone regenerating potential, in combination with an interconnected porous network and a microporosity, known to enhance bone growth and vascularization.
Project description:Cellulose nanocrystals (CNC) are drawing increasing attention in the fields of biomedicine and healthcare owing to their durability, biocompatibility, biodegradability and excellent mechanical properties. Herein, we fabricated using fused deposition modelling technology 3D composite scaffolds from polylactic acid (PLA) and CNC extracted from Ficus thonningii. Scanning electron microscopy revealed that the printed scaffolds exhibit interconnected pores with an estimated average pore size of approximately 400 µm. Incorporating 3% (w/w) of CNC into the composite improved PLA mechanical properties (Young's modulus increased by ~ 30%) and wettability (water contact angle decreased by ~ 17%). The mineralization process of printed scaffolds using simulated body fluid was validated and nucleation of hydroxyapatite confirmed. Additionally, cytocompatibility tests revealed that PLA and CNC-based PLA scaffolds are non-toxic and compatible with bone cells. Our design, based on rapid 3D printing of PLA/CNC composites, combines the ability to control the architecture and provide improved mechanical and biological properties of the scaffolds, which opens perspectives for applications in bone tissue engineering and in regenerative medicine.
Project description:As one of the most transplanted tissues of the human body, bone has varying architectures, depending on its anatomical location. Therefore, bone defects ideally require bone substitutes with a similar structure and adequate strength comparable to native bones. Light-based three-dimensional (3D) printing methods allow the fabrication of biomimetic scaffolds with high resolution and mechanical properties that exceed the result of commonly used extrusion-based printing. Digital light processing (DLP) is known for its faster and more accurate printing than other 3D printing approaches. However, the development of biocompatible resins for light-based 3D printing is not as rapid as that of bio-inks for extrusion-based printing. In this study, we developed CSMA-2, a photopolymer based on Isosorbide, a renewable sugar derivative monomer. The CSMA-2 showed suitable rheological properties for DLP printing. Gyroid scaffolds with high resolution were successfully printed. The 3D-printed scaffolds also had a compressive modulus within the range of a human cancellous bone modulus. Human adipose-derived stem cells remained viable for up to 21 days of incubation on the scaffolds. A calcium deposition from the cells was also found on the scaffolds. The stem cells expressed osteogenic markers such as RUNX2, OCN, and OPN. These results indicated that the scaffolds supported the osteogenic differentiation of the progenitor cells. In summary, CSMA-2 is a promising material for 3D printing techniques with high resolution that allow the fabrication of complex biomimetic scaffolds for bone regeneration.
Project description:Demineralized bone matrix (DBM) is an osteoconductive and osteoinductive commercial biomaterial and approved medical device used in bone defects with a long track record of clinical use in diverse forms. True to its name and as an acid-extracted organic matrix from human bone sources, DBM retains much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates and some trace cell debris. Many of DBM's proteinaceous components (e.g., growth factors) are known to be potent osteogenic agents. Commercially sourced as putty, paste, sheets and flexible pieces, DBM provides a degradable matrix facilitating endogenous release of these compounds to the bone wound sites where it is surgically placed to fill bone defects, inducing new bone formation and accelerating healing. Given DBM's long clinical track record and commercial accessibility in standard forms and sources, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopedic repair and regenerative medicine contexts are attractive.