No abstract

However, it is often challenging to print large free-form tissue structures owing to the inadequate structural integrity and mechanical stability of softhydrogel-based bioink. [4] For the past decade, considerable effort has been made to address this particular challenge. For example, Kang and co-workers proposed a hydrogel reinforcing strategy by coprinting cell-laden hydrogel bioinks with synthetic polycaprolactone (PCL) polymer that serves as a supporting framework. [5] Although this strategy allowed the fabrication of humanscale bone and cartilage tissue constructs, the mechanically robust PCL fibers often impeded the maturation of soft tissue such as the heart and liver. Alternatively, the embedded 3D bioprinting strategy has gained increasing popularity for constructing complex freeform structures. [6] In this approach, a suspension medium is utilized to support the deposition of bioinks in 3D space before crosslinking. The suspension medium undergoes rapid fluidization at yield stress and then solidification in the absence of stress due to its unique shear-thinning and self-healing properties. [7] The printed structures can easily be removed from the suspension medium by gently washing the suspension medium or raising the temperature. As an example of this strategy, Lee and co-workers printed a functional ventricle and full-size human heart model into a gelatin microparticles-based suspension medium by using a freeform reversible embedding of suspended hydrogels, also termed the FRESH technique. [8] Creating functional tissues and organs in vitro on demand is a major goal in biofabrication, but the ability to replicate the external geometry of specific organs and their internal structures such as blood vessels simultaneously remains one of the greatest impediments. Here, this limitation is addressed by developing a generalizable bioprinting strategy of sequential printing in a reversible ink template (SPIRIT). It is demonstrated that this microgel-based biphasic (MB) bioink can be used as both an excellent bioink and a suspension medium that supports embedded 3D printing due to its shear-thinning and self-healing behavior. When encapsulating human-induced pluripotent stem cells, the MB bioink is 3D printed to generate cardiac tissues and organoids by extensive stem cell proliferation and cardiac differentiation. By incorporating MB bioink, the SPIRIT strategy enables the effective printing of a ventricle model with a perfusable vascular network, which is not possible to fabricate using extant 3D printing strategies. This SPIRIT technique offers an unparalleled bioprinting capability to replicate the complex organ geometry and internal structure in a faster manner, which will accelerate the biofabrication and therapeutic applications of tissue and organ constructs.

No abstract

Nerve guidance conduits (NGCs) have become a promising alternative for peripheral nerve regeneration; however, the outcome of nerve regeneration and functional recovery is greatly affected by the physical, chemical, and electrical properties of NGCs. In this study, a conductive multiscale filled NGC (MF-NGC) consisting of electrospun poly(lactide-co-caprolactone) (PCL)/collagen nanofibers as the sheath, reduced graphene oxide /PCL microfibers as the backbone, and PCL microfibers as the internal structure for peripheral nerve regeneration is developed. The printed MF-NGCs presented good permeability, mechanical stability, and electrical conductivity, which further promoted the elongation and growth of Schwann cells and neurite outgrowth of PC12 neuronal cells. Animal studies using a rat sciatic nerve injury model reveal that the MF-NGCs promote neovascularization and M2 transition through the rapid recruitment of vascular cells and macrophages. Histological and functional assessments of the regenerated nerves confirm that the conductive MF-NGCs significantly enhance peripheral nerve regeneration, as indicated by improved axon myelination, muscle weight increase, and sciatic nerve function index. This study demonstrates the feasibility of using 3D-printed conductive MF-NGCs with hierarchically oriented fibers as functional conduits that can significantly enhance peripheral nerve regeneration.

No abstract