3D printing technology and tissue engineering technology in tracheal replacement: Application and hotspot research / 中国组织工程研究

BACKGROUND: Functional tracheal reconstruction remains a surgical challenge due to the lack of satisfactory tracheal substitutes. OBJECTIVE: To review the research hotspot, clinical application, and main obstacles of tissue-engineered trachea METHODS: A computer-based search of PubMed, Medline, and WanFang databases was performed to retrieve relevant articles published from 2004 to 2019 with the search terms “3D printing, tissue-engineered trachea, trachea reconstruction, tracheal replacement” in English and Chinese. A total of 47 literatures were included in the final analysis. RESULTS AND CONCLUSION: At present, the methods of tracheal reconstruction mainly include artificial tracheal transplantation, allotransplantation, autologous tissue transplantation and tissue-engineered tracheal transplantation. Artificial trachea transplants often fail due to rupture, infection and narrowing of the trachea. Allotransplantation requires long-term immunosuppressive therapy, and death is often caused by necrosis and infection because of insufficient angiogenesis after transplantation. Autogenous tissue has limited ability to replicate the structure and function of the trachea and also has surgical trauma. Tissue-engineered trachea can simulate the biological structure and function similar to natural trachea by selecting suitable scaffold materials and implanting seed cells evenly in the scaffold. It seems to be an ideal tracheal substitute. An intact tracheal scaffold was prepared with biodegradable material using 3D printing technology combined with tissue engineering technology and then implanted into the tissue-engineered trachea cultured with mesenchymal stem cells. This provides a new approach to long-segment tracheal defect reconstruction.

A Comparative Study on Cartilage Induction by Bone Morphogenetic Protein Mixed With Different Carriers in Canine Tracheal Autografts / 中国医师杂志

Objective Three soluble materials were used as carrier of recombinant human bone morphogenetic protein-2(rhBMP-2) in order to seek suitable slow-release carrier of rhBMP-2,which induced neogenetic cartilage in canine tracheal autografting segment.Methods 32 mongrel dogs were randomly and equally divided into 4 groups.A five-ring cervical tracheal segment was harvested as the autograft.The materials including dextran,polyvinyl pyrrolidone(PVP) and collagen were respectively combined with equal rhBMP-2 and then injected into the soft tissues between cartilaginous rings of autografts.In addition,without carrier group was used as controls.Then the autografts were heterotopically transplanted into greater omentum.The animals were sacrificed at postoperative 4 weeks,and the postmortem specimens were examined grossly and histologically.Results Cartilage rings of the grafts were partly absorbed in all four groups.New cartilage was induced in the rhBMP-2 injected area in the groups in which PVP or collagen was used as carrier,and more new cartilage was observed in the collagen group.Conclusions PVP and collagen could be sustained as release carriers for rhBMP-2 in tracheal autograft.Collagen is more effective as a carrier than other vehicles and it could enhance the ability of rhBMP-2 inducing cartilage regeneration in tracheal transplantation.

The Morphologic Changes by Immunosuppression after Heterotopic Transplantation of the Murine Cryopreserved Trachea: An Animal Model for Obliterative Bronchiolitis / 대한흉부외과학회지

BACKGROUND: The replacement of the narrowed long-segment trachea with various prosthetic materials or tissue grafts remains a difficult and unsolved surgical problem. Homologous cryopreserved tracheal transplantation has been considered to treat the irreversibly-damaged organs, such as in the lung or heart transplantation and also to overcome the limited supply of donor organs. We examined the morphological changes and the immunosuppressive effects of the cryopreserved trachea after the heterotopic transplantation in the rats. MATERIAL AND METHOD: Sixty tracheal segments harvested from 30 donor Wistar rats were heterotopically implanted into the peritoneal cavity of 20 recipient Wistar rats and 40 Sprague Dawley rats. The 60 recipient rats were divided into 6 groups(10 rats/ group). In groups I, II, and III, 30 tracheal segments were implanted immediately after the harvesting and in groups IV, V, and VI, the segments were implanted 28 days after the cryopreservation. Groups I and IV were Wistar syngeneic controls. Groups II and V were Sprague Dawley recipients receiving no immunosuppression and Groups III and VI, were Sprague Dawley recipients receiving immunosuppressive agents. At 28 days all rats were sacrificed and the tracheal segments were evaluated grossly and histologically. RESULT: Immunosuppression of the tracheal segments had a significant influence on the changes of the tracheal lumen and tracheal epithelial cells, irrespective of the cryopreservation of the trachea(p<0.001). In groups III and VI receiving immunosuppressive agents, the tracheal lumen was patent and the normal epithelial cells were observed, however in the other groups not receiving the immunosuppressive agents, there were almost luminal obliteration by the proliferation of the fibrous tissues and a loss of the epithelial cells, the findings were similar to those in the case of obliterative bronchiolitis after a lung and a heart-lung transplantation. CONCLUSION: With the appropriate immunosuppressive agents, the lumen and the respiratory epithelium of the transplanted tracheal segment were well preserved, even after the cryopreservation of the tracheal segment, which shows the possibility of the long-term preservation and homologous transplantation of the trachea. But fibroproliferative obliteration of the tracheal lumen and the loss of the normal respiratory epithelial cells, characteristic findings of obliterative bronchiolitis, were observed in the groups without the immunosuppression. This experiment using the rat trachea may be useful in studying the pathogenesis, treatment, and prevention of obliterative bronchiolitis after a lung and a heart-lung transplantation.

Effects of the b-FGF to Early Revascularization and Epithelial Regeneration in the Rabbit's Tracheal Autograft / 대한흉부외과학회지

Donor airway ischemia is a significant problem after tracheal replacement with homograft or lung transplantation. Several factors such as omentopexy, heparin, PGI2 and fibroblast growth factor, have been shown to induce angiogenesis in vitro and in vivo. This study was designed to investigate whether omentopexy and basic fibroblast growth factor can enhance rabbit tracheal revascularization and epithelial regeneration. Three different experiments were performed with New Zealand white rabbit. In group I(n=15 control group), only cervical tracheal autotransplantation was done. In group II(n=15), cervical tracheal autotransplantation with omentopexy was done through subcutaneous route. In group III(n=15), cervical tracheal autotransplantation was done and 1ug basic fibroblast growth factor was applied. After 3, 7 and 14 days, the animals were sacrificed. The extent of revascularization was investigated by means of uptake of the human serum albumin labelled with 99m technetium, and epithelial regeneration were assessed by means of light microscope. In the group investigated at day 3, there was statistically significant high tracheal revascularization in group III(p<0.05), but no difference at 7 and 14 days. And epithelial regenerations at day 3 were better in group III(p<0.05), and at day 7 in group II and III. But there was no difference at day 14. We concluded that b-FGF can enhance the revascularization and epithelial regeneration of the tracheal autograft especially in early phase.

The role of omentopexy in tracheal transplantation in dogs

The major step toward successful tracheal transplantation is revascularization of the grafted trachea. There are many reports that although omentopexy is an effective method to facilitate neo-vascularization in tracheal transplantations, the procedure has not been accepted universally in the transplantation field. It remains unclear whether an omentopexy can successfully revascularize tracheal graft regardless of the length of graft. This study was undertaken to assess the usefulness of omentopexy for long-segment(more than 4 cm) tracheal allotransplantation. We have performed six tracheal transplantations with omentopexy (group A) and four tracheal transplantations without omentopexy (group B) in mongrel dogs from July 1993 to February 1995. Five mid-portion tracheal rings were removed from ten donor dogs and ten corresponding tracheal rings were removed from the ten recipient dogs. The excised tracheal rings from the donors were transplanted to the recipient tracheal-excised sites. All the recipients were given cyclosporine, azathioprine, and prednisolone for immunosuppression in the post-operative period. The histologic results of all the surviving members of group B were better than those of the group A. These findings indicate that omentopexy has a limitation, it is not a major method for graft revascularization. Therefore the length of the tracheal graft was greater than 4.0 cm, for its viability, a longer tracheal graft requires some other blood supply aside from the omentopexy.