Mechanical and Physical Characterization of a Biphasic 3D Printed Silk-Infilled Scaffold for Osteochondral Tissue Engineering.

Osteochondral tissue damage is a serious concern, with even minor cartilage damage dramatically increasing an individual's risk of osteoarthritis. Therefore, there is a need for an early intervention for osteochondral tissue regeneration. 3D printing is an exciting method for developing novel scaffolds, especially for creating biological scaffolds for osteochondral tissue engineering.

3D bioassembly of cell-instructive chondrogenic and osteogenic hydrogel microspheres containing allogeneic stem cells for hybrid biofabrication of osteochondral constructs.

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 example in this study, because of the challenges in fabricating load bearing osteochondral tissue constructs with phenotypically distinct zonal architecture.

Hybrid fabrication of photo-clickable vascular hydrogels with additive manufactured titanium implants for enhanced osseointegration and vascularized bone formation.

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 anvascularized bone implant by combining cell-laden hydrogels with direct metal printed (DMP) porous titanium alloys (Ti-6Al-4V).

Development and Characterization of Gelatin-Norbornene Bioink to Understand the Interplay between Physical Architecture and Micro-Capillary Formation in Biofabricated Vascularized Constructs.

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.

Hybrid biofabrication of 3D osteoconductive constructs comprising Mg-based nanocomposites and cell-laden bioinks for bone repair.

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.

Converging functionality: Strategies for 3D hybrid-construct biofabrication and the role of composite biomaterials for skeletal regeneration.

The evolution of additive manufacturing (AM) technologies, biomaterial development and our increasing understanding of cell biology has created enormous potential for the development of personalized regenerative therapies. In the context of skeletal tissue engineering, physical and biological demands play key roles towards successful construct implantation and the achievement of bone, cartilage and blood vessel tissue formation. Nevertheless, meeting such physical and biological demands to mimic the complexity of human tissues and their functionality is still a significant ongoing challenge.

Silk fibroin photo-lyogels containing microchannels as a biomaterial platform for tissue engineering.

The biophysical properties of biomaterials are key to directing the biological responses and biomaterial integration and function in in situ tissue engineering approaches. We present silk photo-lyogels, a biomaterial format fabricated using a new combinatorial approach involving photo-initiated crosslinking of silk fibroin via di-tyrosine bonds followed by lyophilization to generate 3D, porous lyogels showing physical properties distinct to those of lyophilized silk sponges or silk hydrogels. This fabrication approach allowed introduction of microchannels into 3D constructs via biofabrication approaches involving silk crosslinking around an array of 3D printed photocurable resin pillars to generate parallel channels or around a 3D printed sacrificial thermosensitive gel to generate interconnected channels in a rapid manner and without the need for chemical modification of silk fibroin.

Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity.

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 ) while retaining high cell viability (>80%).

Osteogenic and angiogenic tissue formation in high fidelity nanocomposite Laponite-gelatin bioinks.

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.

Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs.

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.