Tracheal resection has limited applicability. Although various tracheal replacement strategies were performed using artificial prosthesis, synthetic stents and tissue transplantation, the best method in tracheal reconstruction remains to be identified. Recent advances in tissue engineering enabled 3D bioprinting using various biocompatible materials including living cells, thereby making the product clinically applicable. Moreover, clinical interest in mesenchymal stem cell has dramatically increased. Here, rabbit bone marrow-derived mesenchymal stem cells (bMSC) and rabbit respiratory epithelial cells were cultured. The chondrogenic differentiation level of bMSC cultured in regular media (MSC) and that in chondrogenic media (d-MSC) were compared. Dual cell-containing artificial trachea were manufactured using a 3D bioprinting method with epithelial cells and undifferentiated bMSC (MSC group, n = 6) or with epithelial cells and chondrogenic-differentiated bMSC (d-MSC group, n = 6). d-MSC showed a relatively higher level of glycosaminoglycan (GAG) accumulation and chondrogenic marker gene expression than MSC in vitro. Neo-epithelialization and neo-vascularization were observed in all groups in vivo but neo-cartilage formation was only noted in d-MSC. The epithelial cells in the 3D bioprinted artificial trachea were effective in respiratory epithelium regeneration. Chondrogenic-differentiated bMSC had more neo-cartilage formation potential in a short period. Nevertheless, the cartilage formation was observed only in a localized area.

Various treatment methods for tracheal defects have been attempted, such as artificial implants, allografts, autogenous grafts, and tissue engineering; however, no perfect method has been established. We attempted to create an effective artificial trachea via a tissue engineering method using 3D bio-printing. A multi-layered scaffold was fabricated using a 3D printer. Polycaprolactone (PCL) and hydrogel were used with nasal epithelial and auricular cartilage cells in the printing process. An artificial trachea was transplanted into 15 rabbits and a PCL scaffold without the addition of cells was transplanted into 6 rabbits (controls). All animals were followed up with radiography, CT, and endoscopy at 3, 6, and 12 months. In the control group, 3 out of 6 rabbits died from respiratory symptoms. Surviving rabbits in control group had narrowed tracheas due to the formation of granulation tissue and absence of epithelium regeneration. In the experimental group, 13 of 15 animals survived, and the histologic examination confirmed the regeneration of epithelial cells. Neonatal cartilage was also confirmed at 6 and 12 months. Our artificial trachea was effective in the regeneration of respiratory epithelium, but not in cartilage regeneration. Additional studies are needed to promote cartilage regeneration and improve implant stability.

Angiogenesis induction into damaged sites has long been an unresolved issue. Local treatment with pro-angiogenic molecules has been the most common approach. However, this approach has critical side effects including inflammatory coupling, tumorous vascular activation, and off-target circulation. Here, the concept that a structure can guide desirable biological function is applied to physically engineer three-dimensional channel networks in implant sites, without any therapeutic treatment. Microchannel networks are generated in a gelatin hydrogel to overcome the diffusion limit of nutrients and oxygen three-dimensionally. Hydrogel implantation in mouse and porcine models of hindlimb ischemia rescues severely damaged tissues by the ingrowth of neighboring host vessels with microchannel perfusion. This effect is guided by microchannel size-specific regenerative macrophage polarization with the consequent functional recovery of endothelial cells. Multiple-site implantation reveals hypoxia and neighboring vessels as major causative factors of the beneficial function. This technique may contribute to the development of therapeutics for hypoxia/inflammatory-related diseases.

Shin JC, et al. Ann Rehabil Med. 2012 Feb;36(1):119-125. http://dx.doi.org/10.5535/arm.2012.36.1.119

Background: Acute acquired comitant esotropia (AACE) is a type of strabismus characterized by a sudden onset of large angle esotropia with diplopia, which often occurs in children after infancy, teenagers, and young adolescents. However, studies on the surgical outcomes of only adults are rare. The purpose of this article is to analyze the surgical outcomes for adult patients diagnosed with AACE. Methods: Medical records of 24 patients who had undergone surgery for AACE were retrospectively analyzed. The main outcome measures were the final motor and sensory success rate after surgery and factors affecting motor and sensory outcomes. Motor success was considered alignment within 8 prism diopter (PD) at both near and distance and sensory success was stereoacuity ≥ 60 sec/arc. Results: The preoperative mean esodeviation angles were 33.1 ± 10.4 PD at distance and 33.3 ± 11.2 PD at near. The mean period of postoperative follow up was 7.5 ± 4.5 months (range 1–8 months). The postoperative mean esodeviation angles at final follow-up time were 3.4 ± 6.1 PD at distance and 3.8 ± 6.7 PD at near. The surgical motor success rate at final follow-up was 79.2% (19/24). The sensory success rate at final follow-up was 50.0% (12/24). The factor affecting the motor outcome was the type of surgery (p < 0.05). The factor affecting sensory outcome was postoperative follow-up time (p < 0.05). Conclusions: Surgery type appears to affect surgical motor outcomes in adults with AACE. Although the sensory outcome was favorable, it seems that regaining bifoveal fixation takes time.