Multimaterial bioprinting approaches and their implementations for vascular and vascularized tissues

Multimaterial bioprinting is a promising technology integrating multimaterial setups into bioprinting platforms for the fabrication of multicellular, heterogeneous and functional tissue constructs. By simultaneously or sequentially dispensing different categories of materials including cell-laden hydrogels or extracellular matrix components, sacrificial materials and scaffolding polymers with hierarchical microarchitecture, multimaterial bioprinting has achieved several milestones for the native tissue biomimicry. Particularly, reconstruction of multiscale, hierarchically branched vascular networks within engineered tissues has been residing as a grand challenge for the fabrication of tissues with long term viability and functionality, which hampers the transition of engineered constructs from research to clinic. To date, various multimaterial bioprinting approaches have been proposed to address the need for fabrication of vascular or vascularized tissues. In this review, a comprehensive overview is given to demonstrate the potential of multimaterial bioprinting technology for the biofabrication of vascular and vascularized tissues. In this regard, different multimaterial bioprinting approaches developed so far are described thoroughly, following the introduction of bioprinting modalities employed in tissue engineering and organization of vascular tissues. Subsequently, multimaterial bioprinting of vascular and vascularized tissues are presented with the main emphasis on the developed fabrication strategies and applied techniques. Comparative evaluation of the multimaterial bioprinting approaches and future perspectives are also delivered to reader

Embedded multimaterial bioprinting platform for biofabrication of biomimetic vascular structures

The advent of bioprinting technology into the tissue engineering field has permitted the attainment of complex-shaped tissue constructs with unprecedented degree of precision and reproducibility, promising for the highly demanded tissue substitutes including vascular grafts. However, most of the bioprinted vascular tissue substitutes still lack multicellular composition and hierarchical complexity of native blood vessels. In this study, a multimaterial bioprinting platform incorporating multiple-channel microfluidic printhead was combined with embedded bioprinting technique for the fabrication of vascular-like constructs. Three different bioink formulations targeting intimal, medial, and adventitial zones of the natural vascular tissues were sequentially extruded from the microfluidic channels of printhead into a hydrogel-nanoclay support bath in a controlled manner to reach the biomimicry of vascular tissues. The results demonstrated the successful deposition of three bioink compositions into distinct zones within hollow structures, which would provide an opportunity for the construction of functional vascular substitutes. Graphic abstract: [Figure not available: see fulltext.

Gold Nanoparticles in Single-Cell Analysis for Surface Enhanced Raman Scattering

The need for new therapeutic approaches in the treatment of challenging diseases such as cancer, which often consists of a highly heterogeneous and complex population of cells, brought up the idea of analyzing single cells. The development of novel techniques to analyze single cells has been intensively studied to fully understand specific alternations inducing abnormalities in cellular function. One of the techniques used for single cell analysis is surface-enhanced Raman spectroscopy (SERS) in which a noble metal nanoparticle is used to enhance Raman scattering. Due to its low toxicity and biocompatibility, gold nanoparticles (AuNPs) are commonly preferred as SERS substrates in single cell analysis. The intracellular uptake, localization and toxicity issues of AuNPs are the critical points for interpretation of data since the obtained SERS signals originate from molecules in close vicinity to AuNPs that are taken up by the cells. In this review, the AuNP–living cell interactions, cellular uptake and toxicity of AuNPs in relation to their physicochemical properties, and surface-enhanced Raman scattering from single cells are discussed

Multimaterial bioprinting approaches and their implementations for vascular and vascularized tissues

Multimaterial bioprinting is a promising technology integrating multimaterial setups into bioprinting platforms for the fabrication of multicellular, heterogeneous and functional tissue constructs. By simultaneously or sequentially dispensing different categories of materials including cell-laden hydrogels or extracellular matrix components, sacrificial materials and scaffolding polymers with hierarchical microarchitecture, multimaterial bioprinting has achieved several milestones for the native tissue biomimicry. Particularly, reconstruction of multiscale, hierarchically branched vascular networks within engineered tissues has been residing as a grand challenge for the fabrication of tissues with long term viability and functionality, which hampers the transition of engineered constructs from research to clinic. To date, various multimaterial bioprinting approaches have been proposed to address the need for fabrication of vascular or vascularized tissues. In this review, a comprehensive overview is given to demonstrate the potential of multimaterial bioprinting technology for the biofabrication of vascular and vascularized tissues. In this regard, different multimaterial bioprinting approaches developed so far are described thoroughly, following the introduction of bioprinting modalities employed in tissue engineering and organization of vascular tissues. Subsequently, multimaterial bioprinting of vascular and vascularized tissues are presented with the main emphasis on the developed fabrication strategies and applied techniques. Comparative evaluation of the multimaterial bioprinting approaches and future perspectives are also delivered to reader

Biomimicry in bio-manufacturing: developments in melt electrospinning writing technology towards hybrid biomanufacturing

Melt electrospinning writing has been emerged as a promising technique in the field of tissue engineering, with the capability of fabricating controllable and highly ordered complex three-dimensional geometries from a wide range of polymers. This three-dimensional (3D) printing method can be used to fabricate scaffolds biomimicking extracellular matrix of replaced tissue with the required mechanical properties. However, controlled and homogeneous cell attachment on melt electrospun fibers is a challenge. The combination of melt electrospinning writing with other tissue engineering approaches, called hybrid biomanufacturing, has introduced new perspectives and increased its potential applications in tissue engineering. In this review, principles and key parameters, challenges, and opportunities of melt electrospinning writing, and particularly, recent approaches and materials in this field are introduced. Subsequently, hybrid biomanufacturing strategies are presented for improved biological and mechanical properties of the manufactured porous structures. An overview of the possible hybrid setups and applications, future perspective of hybrid processes, guidelines, and opportunities in different areas of tissue/organ engineering are also highlighted

Preparation and characterization of nanoclay-hydrogel composite support-bath for bioprinting of complex structures

Three-dimensional bioprinting of cell-laden hydrogels in a sacrificial support-bath has recently emerged as a potential solution for fabricating complex biological structures. Physical properties of the support-bath strongly influence the bioprinting process and the outcome of the fabricated constructs. In this study, we reported the application of a composite Pluronic-nanoclay support-bath including calcium ions as the crosslinking agent for bioprinting of cell-laden alginate-based hydrogels. By tuning the rheological properties, a shear-thinning composite support-bath with fast self-recovery behavior was yielded, which allowed continuous printing of complex and large-scale structures. The printed structures were easily and efficiently harvested from the support-bath without disturbing their shape fidelity. Moreover, the results showed that support-bath assisted bioprinting process did not influence the viability of cells encapsulated within hydrogel. This study demonstrates that Pluronic-nanoclay support-bath can be utilized for bioprinting of complex, cell-laden constructs for vascular and other tissue engineering applications

Functional Hydrogels for Treatment of Chronic Wounds

Chronic wounds severely affect 1–2% of the population in developed countries. It has been reported that nearly 6.5 million people in the United States suffer from at least one chronic wound in their lifetime. The treatment of chronic wounds is critical for maintaining the physical and mental well-being of patients and improving their quality of life. There are a host of methods for the treatment of chronic wounds, including debridement, hyperbaric oxygen therapy, ultrasound, and electromagnetic therapies, negative pressure wound therapy, skin grafts, and hydrogel dressings. Among these, hydrogel dressings represent a promising and viable choice because their tunable functional properties, such as biodegradability, adhesivity, and antimicrobial, anti-inflammatory, and pre-angiogenic bioactivities, can accelerate the healing of chronic wounds. This review summarizes the types of chronic wounds, phases of the healing process, and key therapeutic approaches. Hydrogel-based dressings are reviewed for their multifunctional properties and their advantages for the treatment of chronic wounds. Examples of commercially available hydrogel dressings are also provided to demonstrate their effectiveness over other types of wound dressings for chronic wound healing

Embedded 3D printing of cryogel-based scaffolds

Cryogel-based scaffolds have attracted great attention in tissue engineering due to their interconnected macroporous structures. However, three-dimensional (3D) printing of cryogels with a high degree of precision and complexity is a challenge, since the synthesis of cryogels occurs under cryogenic conditions. In this study, we demonstrated the fabrication of cryogel-based scaffolds for the first time by using an embedded printing technique. A photo-cross-linkable gelatin methacryloyl (GelMA)-based ink composition, including alginate and photoinitiator, was printed into a nanoclay-based support bath. The layer-by-layer extruded ink was held in complex and overhanging structures with the help of pre-cross-linking of alginate with Ca2+ present in the support bath. The printed 3D structures in the support bath were frozen, and then GelMA was cross-linked at a subzero temperature under UV light. The printed and cross-linked structures were successfully recovered from the support bath with an integrated shape complexity. SEM images showed the formation of a 3D printed scaffold where porous GelMA cryogel was integrated between the cross-linked alginate hydrogels. In addition, they showed excellent shape recovery under uniaxial compression cycles of up to 80% strain. In vitro studies showed that the human fibroblast cells attached to the 3D printed scaffold and displayed spread morphology with a high proliferation rate. The results revealed that the embedded 3D printing technique enables the fabrication of cytocompatible cryogel based scaffolds with desired morphology and mechanical behavior using photo-cross-linkable bioink composition. The properties of the cryogels can be modified by varying the GelMA concentration, whereby various shapes of scaffolds can be fabricated to meet the specific requirements of tissue engineering applications