Control of immunogenic responses of microorganism-synthesized biopolymers for 3D bioprinting tissue engineering and regenerative medicine.

Different biopolymers are synthesized by diverse microorganisms through cell and genetic engineering for their applications to organoids, tissue engineering, and regenerative medicine with advanced technologies such as 3D bioprinting, microfluidics, and others. All living bodies repair or replenish their tissues, organs, and systems by synthesizing different biopolymers secreted into their extracellular matrix. Microbially synthesized biopolymers have an advantage over the bulk-synthesized ones due to precise control over the synthesis process, resulting in a tunable molecular structure, molecular weight, and other important properties. This provides an edge over traditional biomaterials as immunomodulatory during tissue engineering. For clinical applications of tissue engineering, the employed biopolymers should be of medical grade with controlled immunogenic responses during and after their implantation, offering precision fabrication of tissue engineering scaffolds and adequate functional tissue regeneration by replacing the scaffolds with their matching biodegradation rates. This review focuses on control of immunogenic responses caused by microorganism-synthesized biopolymers in their applications to 3D bioprinting and other tissue engineering modalities. The synthesis, fermentation, and purification processes of microbial biopolymers and their applications in 3D bioprinted tissue engineering are explained in brief for different exopolysaccharides, proteins, polypeptides, and polyesters. The contents are focused on the preparation of medical-grade polymers, their limited chemical uses, and green and sustainable approaches for the functionalization of polymers and hydrogels in tissue engineering. The immunogenic responses (mostly innate), strategies to control them, and related advantages and concerns are mainly discussed in detail, targeting their successful clinical implementation in the 3D bioprinting-based and other tissue regeneration and reconstruction domains.