It is difficult to fabricate tubular-shaped tissues and organs (e.g., trachea, blood vessel, and esophagus tissue) with traditional biofabrication techniques (e.g., electrospinning, cell-sheet engineering, and mold-casting) because these have complicated multiple processes. In addition, the tubular-shaped tissues and organs have their own design with target-specific mechanical and biological properties. Therefore, the customized geometrical and physiological environment is required as one of the most critical factors for functional tissue regeneration. 3D bioprinting technology has been receiving attention for the fabrication of patient-tailored and complex-shaped free-form architecture with high reproducibility and versatility. Printable biocomposite inks that can facilitate to build tissue constructs with polymeric frameworks and biochemical microenvironmental cues are also being actively developed for the reconstruction of functional tissue. In this review, we delineated the state-of-the-art of 3D bioprinting techniques specifically for tubular tissue and organ regeneration. In addition, this review described biocomposite inks, such as natural and synthetic polymers. Several described engineering approaches using 3D bioprinting techniques and biocomposite inks may offer beneficial characteristics for the physiological mimicry of human tubular tissues and organs.

The incidences of various esophageal diseases (e.g., congenital esophageal stenosis, tracheoesophageal fistula, esophageal atresia, esophageal cancer) are increasing, but esophageal tissue is difficult to be recovered because of its weak regenerative capability. There are no commercialized off-the-shelf alternatives to current esophageal reconstruction and regeneration methods. Surgeons usually use ectopic conduit tissues including stomach and intestine, presumably inducing donor site morbidity and severe complications. To date, polymer-based esophageal substitutes have been studied as an alternative. However, the fabrication techniques are nearly limited to creating only cylindrical outer shapes with the help of additional apparatus (e.g., mandrels for electrospinning) and are unable to recapitulate multi-layered characteristic or complex-shaped inner architectures. 3D bioprinting is known as a suitable method to fabricate complex free-form tubular structures with desired pore characteristic. In this study, we developed a extrusion-based 3D printing technique to control the size and the shape of the pore in a single extrusion process, so that the fabricated structure has a higher flexibility than that fabricated in the conventional process. Based on this suggested technique, we developed a bioprinted 3D esophageal structure with multi-layered features and converged with biochemical microenvironmental cues of esophageal tissue by using decellularizedbioinks from mucosal and muscular layers of native esophageal tissues. the two types of esophageal tissue deriveddecellularized extracellular matrix bioinks can mimic the inherent components and composition of original tissues with layer specificity. This structure can be applied to full-thickness circumferential esophageal defects and esophageal regeneration. The esophageal tissue refers to the hollow organ between the oropharynx and the stomach, which allows food to pass to the stomach through peristalsis. Congenital or acquired esophageal disorders such as esophageal cancer, malignancy, and esophageal achalasia usually require reconstruction of the defect site after the surgery and stomach, small and large intestine, and skin tissues are used to repair the esophagus tissues 1-3. Unfortunately, surgical resection and ablation can cause postoperative complications and various surgical morbidities 4-6. Therefore, a tissue engineering-based approach has been proposed as a promising alternative for reconstruction of circumferential esophageal defects 7-9 .

Dental implant surgeries involve the insertion of implant fixtures into alveolar bones to replace missing teeth. When the availability of alveolar bone at the surgical site is insufficient, bone graft particles are filled in the insertion site for successful bone reconstruction. Bone graft particles induce bone regeneration over several months at the insertion site. Subsequently, implant fixtures can be inserted at the recipient site. Thus, conventional dental implant surgery is performed in several steps, which in turn increases the treatment period and cost involved. Therefore, to reduce surgical time and minimize treatment costs, a novel hybrid scaffold filled with bone graft particles that could be combined with implant fixtures is proposed. This scaffold is composed of a three-dimensionally (3D) printed polycaprolactone (PCL) frame and osteoconductive ceramic materials such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Herein, we analyzed the porosity, internal microstructure, and hydrophilicity of the hybrid scaffold. Additionally, Saos-2 cells were used to assess cell viability and proliferation. Two types of control scaffolds were used (a 3D printed PCL frame and a hybrid scaffold without HA/β-TCP particles) for comparison, and the fabricated hybrid scaffold was verified to retain osteoconductive ceramic particles without losses. Moreover, the fabricated hybrid scaffold had high porosity and excellent microstructural interconnectivity. The in vitro Saos-2 cell experiments revealed superior cell proliferation and alkaline phosphatase assay results for the hybrid scaffold than the control scaffold. Hence, the proposed hybrid scaffold is a promising candidate for minimizing cost and duration of dental implant surgery.

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This study evaluated 3D printed polycaprolactone (PCL) composite scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2), loaded either onto a PCL composite scaffold or implant surface, for vertical bone augmentation with implant placement. Three-dimensional printed PCL frames were filled with powdered PCL, hydroxyapatite, and β-tricalcium phosphate. RhBMP-2 was loaded to the PCL composite scaffolds and implant surfaces, and rhBMP-2 release was quantified for 21 days. Experimental implants were placed bilaterally on 20 rabbit calvaria, and the PCL composite scaffolds were vertically augmented. The randomly allocated experimental groups were divided by carrier and rhBMP-2 dosage as no rhBMP-2 (control), 5 μg rhBMP-2 loaded to PCL composite (Scaffold/rhBMP-2[5 μg]), 5 μg rhBMP-2 loaded to implant (Implant/rhBMP-2[5 μg]), 30 μg rhBMP-2 loaded to PCL composite (Scaffold/rhBMP-2[30 μg]), and 30 μg rhBMP-2 loaded to implant (Implant/rhBMP-2 [30 μg]). Histologic and histometric analyses were conducted after 8 weeks. In both scaffold-loading and implant-loading, rhBMP-2 released initially rapidly, then slowly and constantly. Released rhBMP-2 totaled 23.02 ± 1.03% and 24.69 ± 1.14% in the scaffold-loaded and implant-loaded groups, respectively. There were no significant differences in histologic bone-implant contact (%). Peri-implant bone density (%) was significantly higher in the Scaffold/rhBMP-2(30 μg) and Implant/rhBMP-2(30 μg) groups. Total bone density (%) was not significantly different between the Scaffold/ rhBMP-2(5 μg), Implant/rhBMP-2(5 μg), and control groups, or between the Scaffold/rhBMP-2(30 μg) and Implant/rhBMP-2(30 μg) groups, but was significantly higher in the Scaffold/rhBMP-2(30 μg) and Implant/rhBMP-2(30 μg) groups than in the controls. Three-dimensional printed PCL composite scaffold with rhBMP-2 produced vertical osteogenesis and osseointegration, regardless of rhBMP-2 loading to the PCL composite scaffold or implant surface.Yun-Young Chang and Sa-Ya Lee contributed equally to this study.