Three-dimensional (3D) bioprinting is a novel technique applied to manufacture semisolid or solid objects via deposition of successive thin layers. The widespread implementation of the 3D bioprinting technology encouraged scientists to evaluate its feasibility for applications in human regenerative medicine. 3D bioprinting gained much interest as a new strategy to prepare implantable 3D tissues or organs, tissue and organ evaluation models to test drugs, and cell/material interaction systems. The present work summarizes recent and relevant progress based on the use of hydrogels for the technology of 3D bioprinting and their emerging biomedical applications. An overview of different 3D printing techniques in addition to the nature and properties of bioinks used will be described with a focus on hydrogels as suitable bioinks for 3D printing. A comprehensive overview of triblock copolymers with emphasis on Pluronic F127 (PF127) as a bioink in 3D printing for regenerative medicine will be provided. Several biomedical applications of PF127 in tissue engineering, particularly in bone and cartilage regeneration and in vascular reconstruction, will be also discussed. Impact statement: The current review highlights the use of three-dimensional (3D) bioprinting for regenerative medicine, stressing the manipulation of hydrogels as the most commonly used bioinks. The advantages and shortcomings of using hydrogels for 3D printing procedures are discussed with a particular focus on triblock copolymers and Pluronics. A brief overview of applying bioink Pluronic F127 in applications of 3D bioprinting for tissue reconstruction is also provided.

Parkinson’s disease (PD) is the second most common progressive age-related neurodegenerative disorder. Paramount evidence shed light on the role of PI3K/AKT signaling activation in the treatment of neurodegenerative disorders. PI3K/AKT signaling can be activated via cAMP-dependent pathways achieved by phosphodiesterase 4 (PDE4) inhibition. Roflumilast is a well-known PDE4 inhibitor that is currently used in the treatment of chronic obstructive pulmonary disease. Furthermore, roflumilast has been proposed as a favorable candidate for the treatment of neurological disorders. The current study aimed to unravel the neuroprotective role of roflumilast in the rotenone model of PD in rats. Ninety male rats were allocated into six groups as follows: control, rotenone (1.5 mg/kg/48 h, s.c.), L-dopa (22.5 mg/kg, p.o), and roflumilast (0.2, 0.4 or 0.8 mg/kg, p.o). All treatments were administrated for 21 days 1 h after rotenone injection. Rats treated with roflumilast showed an improvement in motor activity and coordination as well as preservation of dopaminergic neurons in the striatum. Moreover, roflumilast increased cAMP level and activated the PI3K/AKT axis via stimulation of CREB/BDNF/TrkB and SIRT1/PTP1B/IGF1 signaling cascades. Roflumilast also caused an upsurge in mTOR and Nrf2, halted GSK-3β and NF-ĸB, and suppressed FoxO1 and caspase-3. Our study revealed that roflumilast exerted neuroprotective effects in rotenone-induced neurotoxicity in rats. These neuroprotective effects were mediated via the crosstalk between CREB/BDNF/TrkB and SIRT1/PTP1B/IGF1 signaling pathways which activates PI3K/AKT trajectory. Therefore, PDE4 inhibition is likely to offer a reliable persuasive avenue in curing PD via PI3K/AKT signaling activation. Graphical Abstract