3D-Bioprinted Constructs that Breathe

An old but still hot topic in tissue engineering (TE) is the establishment of efficient vascularization networks proving fine, controlled, and long-term distribution oxygen nutrients. Combining elegant three-dimensional (3D) fabrication techniques with unconventional living microorganisms, namely photosynthetic species, complex 3D-printed TE constructs are proposed by Maharjan et al. enabling to provide a continuous on demand supply mammalian tissues. Following implantation bioengineered systems, series well-orchestrated biological processes occur aiming towards repair regeneration.1Lee K. Silva E.A. Mooney D.J. Growth factor delivery-based engineering: general approaches review recent developments.J. R. Soc. Interface. 2011; 8: 153-170Crossref PubMed Scopus (955) Google Scholar While vitro delivery essential biomolecules assuring cell survival can be more easily circumvented, using for example culture apparatus such as perfusion bioreactors, most engineered strategies fail upon implantation. In vivo, dictated 100-200 ?m distance from nearest capillary, thus implanted biomaterials have rely vascular network Deprived that, hypoxic regions generated, consequently proliferation significantly jeopardized, well other important cellular processes, gene expression matrix deposition. Ultimately, either absence network, or its delayed establishment, death microtissue necrosis occur, specially at inner constructs. Considering that situations demanding intervention often those include large defects, otherwise solved innate self-healing human body, proper even critical, challenging, clinical-relevant 3D artificial strategies. Different been overcome nutrient mass transport limitations constructs, ranging (1) systems functionalized key binding sites (Figure 1i) guide facilitate angiogenesis (e.g. integrins, growth factors);2Li S. Nih L.R. Bachman H. Fei P. Li Y. Nam E. Dimatteo Carmichael S.T. Barker T.H. Segura T. Hydrogels precisely controlled integrin activation dictate patterning permeability.Nat. Mater. 2017; 16: 953-961Crossref (101) (2) based void-spaced liquified structures enhance diffusion ingrowth – devices produced sophisticated techniques, bioprinting electrospinning-based approaches, enable high geometrical precision, playing bulk features 1ii-a), architecture porosity,3Kapfer S.C. Hyde Mecke Arns C.H. Schröder-Turk G.E. Minimal surface scaffold designs engineering.Biomaterials. 32: 6875-6882Crossref (271) bottom-up 1ii-b), encapsulation liquefied environments;4Correia C.R. Nadine Mano J.F. Cell Encapsulation Systems Toward Modular Tissue Regeneration: From Immunoisolation Multifunctional Devices.Adv. Funct. 2020; 30: 1908061Crossref (9) Scholar,5Correia Bjørge I.M. Zeng J. Matsusaki M. Liquefied Microcapsules Dual-Microcarriers 3D+ Bottom-Up Engineering.Adv. Healthc. 2019; 1901221Crossref (10) (3) prevascularized scaffolds 1iii).6Guo Redenski I. Landau Szklanny A. Merdler U. Levenberg Prevascularized Scaffolds Bearing Human Dental Pulp Stem Cells Treating Complete Spinal Cord Injury.Adv. 9: 2000974Crossref (17) However, vivo functional remains major challenge. decorated timely arrival specific cells possess inherent ability self-organize achieve this stage, being limited spatiotemporal feature, prefabricated present capacity anastomose host network. Additionally, also physical barriers block vessels, resultant biomaterial content itself deposited extracellular matrix. besides failing healing process target tissue, gradients led generation following trigger tumor microenvironments affecting metabolic, inflammatory, differentiation pathways endogenous subsets. It understand why one main challenges need taken bring into clinical practice scale. As such, an community. More recently, attempt associated road blocks poorly vascularized plethora materials able release 1iv-a) proposed.7Camci-Unal G. Alemdar N. Annabi Khademhosseini Oxygen Releasing Biomaterials Engineering.Polym. Int. 2013; 62: 843-848Crossref (85) Such oxygen-releasing composed solid peroxides calcium magnesium peroxides), hydrogen peroxide, sodium percarbonate, fluorinated compounds. burst arises cytotoxic concerns, short-term curves. To these limitations, suppliers relying co-culture organisms, species 1iv-b), microalgae,8Chávez M.N. Schenck T.L. Hopfner Centeno-Cerdas C. Somlai-Schweiger Schwarz Machens H.-G. Heikenwalder Bono M.R. Allende M.L. al.Towards autotrophic Photosynthetic therapy regeneration.Biomaterials. 2016; 75: 25-36Crossref (51) bacteria.9Li W. Wang Zhong D. Du Z. Zhou A Bioactive Living Hydrogel: Bacteria Mediated Hypoxia Elimination Bacteria-Killing Promote Infected Wound Healing.Adv. Ther. 2000107: 1Google applications wound healing, cancer therapy, cardiovascular related diseases, transplantation. issue Matter, al.10Maharjan Alva Cámara Rubio A.G. Hernández Delavaux al.Bionic Oxygenation within 3D-Bioprinted Vascularized Tissues.Matter. 4Google take step further development embedding bioprinted algae (C. reinhardtii) (HepG2) gelatin methacryloyl-based hydrogel create honeycomb-shaped mimicking liver. The was light conditions, enhanced production liver-specific proteins. Remarkably, authors were produce microchannels taking advantage enzymatic degradation cellulose-based bioink. Afterwards, created repopulating hollow endothelial (C2C12). These findings open door prospect next-generation use components algae. We preview organelles microorganisms may explored, chloroplasts, since they exhibit similar potential unlimited oxygen. believe contribute improve bioperformance act light-responsive drug systems. Detailed understanding organisms used combination biomaterials, producing pathways, adequate balance conditions suitable both cells, prerequisites considered design order develop fully organism-based system, it all surrounding factors type microalgae medium, temperature range, intensity mutually accepted which distinct optimal conditions. truly microorganisms-based harnesses sustainable, eco-friendly, cost-effective source considerable advantages field. Of course, translation clinics will hindered regulatory constrains should addressed future. Funding Portuguese Foundation Science Technology ( CIRCUS-PTDC/BTM-MAT/31064/2017 , CICECO -Aveiro Institute Materials- UIDB/50011/2020 & UIDP/50011/2020 ), European Research Council ERC-2014-ADG-669858-ATLAS ). acknowledge Sara help Figure 1. Symbiotic TissuesMaharjan al.MatterNovember 18, 2020In BriefThree-dimensional-bioprinted unicellular green algae, Chlamydomonas reinhardtii, sustainable bionic O2 photosynthetically improved viability functionality matrices while reducing their Fugitive patterns encapsulating enzymatically dissolved cellulase digestion interconnected microchannels, subsequently endothelialized, generating Full-Text PDF Open Archive