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Revolutionising Airway Reconstructive Surgery: The Promise of 3D Bioprinting Created By: Alyssa Hadjikakou The Clinical Problem Design Approaches Airway Stents: An essential part of our respiratory system, the trachea, can become narrowed or damaged due to various conditions such as thyroid cancer, ● Bioresorbable PDS stents used in 6 post-transplant patients (Lischke et al.) congenital anomalies, and trauma. Traditional treatments frequently fail to ● All initially successful; 4 required re-stenting at ~5 restore the trachea to its former state, however, the advent of 3D months bioprinting technology offers a new approach, potentially revolutionising ● No stent migration or bleeding reported; 5 of 6 patients the reconstruction of airway defects and providing new hope for patients were intervention-free for up to 44 months with severe and complex issues. [1] Non-Circumferential Patches: ● PCL patches used to repair partial tracheal defects ● Rehmani et al.: 4 cm defects reconstructed in pigs; 5/7 The Bioprinting Process survived full 3-month period The bioprinting process begins with a CT scan of the trachea, which is ● Postmortem showed mucosal regeneration, vascularity, and integration then converted to a digital file in order to be readable by the printer. The ● Townsend et al.: In sheep, large patches caused printer works much like an everyday office printer, with ink, bio-ink in this distress; 4/5 euthanised early case, which consists of a biocompatible material such as hydrogel and ● Highlights importance of size/design precision for safe various cell types, often taken directly from the patient to ensure optimal application histocompatibility. There are different forms of bioprinting, with Circumferential Grafts: ● Full tracheal rings more prone to granulation and extrusion-based bioprinting being the most commercially used, where the cell-enriched bioink and scaffold material (usually a biodegradable stenosis ● Lee et al.: Immunosuppression (e.g., cyclosporine) polymer) are loaded into cartridges, which are then attached to showed no benefit and caused side effects printheads, once researchers manually set specific parameters, the Mini-Plates: machine begins to print layer by layer to produce the desired tracheal ● PLA scaffolds seeded with chondrocytes + collagen shape. Once the printing is complete, the structure must be stabilised via ● Implanted in 9 rabbits; all survived, with no granulation the process of crosslinking in which the construct is treated with UV light or scarring ● Histology showed new cartilage formation and or ionic solution; upon completion, the researchers may then submerge the trachea into an appropriate cell medium and place it within an mucosal coverage incubator to allow for cell cultivation.[2] The 3D bio-print is now ready to be surgically implanted within the patient. Scaffold Material Which scaffold material is superior is debated within the scientific community, with the desired quality being biodegradable, biocompatible, mechanically stable, and promote tissue integration. ● Poly-ɛ-caprolactone (PCL) is favoured for long-term implants due to its mechanical strength, low porosity, and structural similarity to native tracheal cartilage. Human Trial ● Polylactic acid (PLA), while FDA-approved, lacks the mechanical Surgeons at Seoul St. Mary’s Hospital successfully properties needed for dynamic structures. implanted a custom 3D bioprinted trachea in a woman with ● Polyglycolic acid (PGA) and poly lactic-co-glycolic acid (PLGA) airway loss after thyroid cancer surgery. offer high porosity and rapid resorption, enabling ● Scaffold: Polycaprolactone (PCL) for strength and neovascularization, but their poor mechanical stability limits their slow degradation use in load-bearing applications. ● Bioink: Mucosal cells from nasal stem cells + donor Hydrogels & Cell Sources cartilage cells Hydrogels support cell delivery and tissue regeneration, often made from ● Printed using patient-specific CT data with a T&R natural materials like collagen, ECM, and hyaluronic acid. These offer Biofab printer excellent biocompatibility and promote neovascularization, but lack 6-month outcome: mechanical strength. ● Full graft integration Solution: Combine natural hydrogels with synthetic scaffolds (e.g., PCL) ● New blood vessel formation for both biological and structural integrity. ● No major complications Cell types used: ● Chondrocytes – Ideal for cartilage regeneration but limited in availability ● 2024 Jul 20]. Available from: https://3dprint.com/308217/worlds-first-bioprinted-trachea-transplant-marks-a-new-era-in-medical-innovation/ting / Additive Manufacturing. 2024 [cited ● Frejo L, Grande DA. 3D-bioprinted tracheal reconstruction: an overview. Bioelectronic Medicine [Internet]. 2019 Sep 17 [cited 2022 Feb 16];5:15. Available from: ● Mesenchymal Stem Cells (MSCs) – Pluripotent; can differentiate ● Townsend JM, Ott LM, Salash JR, Fung KM, Easley JT, Seim HB, et al. Reinforced Electrospun Polycaprolactone Nanofibers for Tracheal Repair in an In Vivo Ovine Model.-Thoracic ● Ann Thorac Surg [Internet]. 2017;104(3):998–1004. Available from: http://dx.doi.org/10.1016/j.athoracsur.2017.03.051al grafts: Preclinical results and potential for human use. into chondrocytes when cultured with appropriate signals (e.g., in ● Goldstein TA, Smith BD, Zeltsman D, Grande D, Smith LP. Introducing a 3‐dimensionally Printed, Tissue‐Engineered Graft for Airway Reconstruction. Otolaryngology–Head and a ● Kwon SK, Song JJ, Cho CG, Park SW, Kim JR, Oh SH, et al. Tracheal reconstruction with asymmetrically porous polycaprolactone/pluronic F127 membranes. Head & Neck. 2013 hydrogel + chondrocyte co-culture) ● Schwarz S, Koerber L, Elsaesser AF, Goldberg-Bockhorn E, Seitz AM, Dürselen L, et al. Decellularized Cartilage Matrix as a Novel Biomatrix for Cartilage Tissue-Engineering This combined strategy enhances both the functional and mechanical ● reconstruction. Biomaterials [Internet]. 2018;185:276–83. Available from: http://dx.doi.org/10.1016/j.biomaterials.2018.09.031D) printing for extensive circumferential tracheal ● https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098220/tion: an overview. Bioelectronic Medicine [Internet]. 2019 Sep 17 [cited 2022 Feb 16];5:15. Available from:engineered success of bioprinted tracheal implants. ● ABaIWorlFir3DPriTracSucceTranspinSouKor[Int3Dnat202Avaifrom:rinted-trachea-transplant-marks-a-new-era-in-medical-innovation/ice of 3D Printing / Additive Manufacturing. 2024. https://www.3dnatives.com/en/worlds-first-3d-printed-trachea-transplanted-in-south-korea-200320246/