Emerging perspectives on 3D printed bioreactors for clinical translation of engineered and bioprinted tissue constructs.

3D printed/bioprinted tissue constructs are utilized for the regeneration of damaged tissues and as in vitro models. Most of the fabricated 3D constructs fail to undergo functional maturation in conventional in vitro settings. There is a challenge to provide a suitable niche for the fabricated tissue constructs to undergo functional maturation. Bioreactors have emerged as a promising tool to enhance tissue maturation of the engineered constructs by providing physical/biological cues along with a controlled nutrient supply under dynamic in vitro conditions. Bioreactors provide an ambient microenvironment most appropriate for the development of functionally matured tissue constructs by promoting cell proliferation, differentiation, and maturation for transplantation and drug screening applications. Due to the huge cost and limited availability of commercial bioreactors, there is a need to develop strategies to make customized bioreactors. Additive manufacturing (AM) may be a viable tool to fabricate custom designed bioreactors with better efficiency and at low cost. In this review, we have extensively discussed the importance of bioreactors in functionalizing tissue engineered/3D bioprinted scaffolds for bone, cartilage, skeletal muscle, nerve, and vascular tissue. In addition, the importance and fabrication of customized 3D printed bioreactors for the maturation of tissue engineered constructs are discussed in detail. Finally, the current challenges and future perspectives in translating commercial and custom 3D printed bioreactors for clinical applications are outlined.

Additive manufacturing of peripheral nerve conduits - Fabrication methods, design considerations and clinical challenges.

Tissue-engineered nerve guidance conduits (NGCs) are a viable clinical alternative to autografts and allografts and have been widely used to treat peripheral nerve injuries (PNIs). Although these NGCs are successful to some extent, they cannot aid in native regeneration by improving native-equivalent neural innervation or regrowth. Further, NGCs exhibit longer recovery period and high cost limiting their clinical applications. Additive manufacturing (AM) could be an alternative to the existing drawbacks of the conventional NGCs fabrication methods. The emergence of the AM technique has offered ease for developing personalized three-dimensional (3D) neural constructs with intricate features and higher accuracy on a larger scale, replicating the native feature of nerve tissue. This review introduces the structural organization of peripheral nerves, the classification of PNI, and limitations in clinical and conventional nerve scaffold fabrication strategies. The principles and advantages of AM-based techniques, including the combinatorial approaches utilized for manufacturing 3D nerve conduits, are briefly summarized. This review also outlines the crucial parameters, such as the choice of printable biomaterials, 3D microstructural design/model, conductivity, permeability, degradation, mechanical property, and sterilization required to fabricate large-scale additive-manufactured NGCs successfully. Finally, the challenges and future directions toward fabricating the 3D-printed/bioprinted NGCs for clinical translation are also discussed.

Advances in electrospinning and 3D bioprinting strategies to enhance functional regeneration of skeletal muscle tissue.

Skeletal muscles are essential for body movement, and the loss of motor function due to volumetric muscle loss (VML) limits the mobility of patients. Current therapeutic approaches are insufficient to offer complete functional recovery of muscle damages. Tissue engineering provides viable ways to fabricate scaffolds to regenerate damaged tissues. Hence, tissue engineering options are explored to address existing challenges in the treatment options for muscle regeneration. Electrospinning is a widely employed fabrication technique to make muscle mimetic nanofibrous scaffolds for tissue regeneration. 3D bioprinting has also been utilized to fabricate muscle-like tissues in recent times. This review discusses the anatomy of skeletal muscle, defects, the healing process, and various treatment options for VML. Further, the advanced strategies in electrospinning of natural and synthetic polymers are discussed, along with the recent developments in the fabrication of hybrid scaffolds. Current approaches in 3D bioprinting of skeletal muscle tissues are outlined with special emphasis on the combination of electrospinning and 3D bioprinting towards the development of fully functional muscle constructs. Finally, the current challenges and future perspectives of these convergence techniques are discussed.