Application And Research A Novel Meta-stable β-type Titanium Alloy Prosthesis In Replacement Of Larynx And Tracheal Defect

Larynx and tracheal defect caused by a variety of reasons is a common and frequently-occurring disease in otolaryngology. There is no standard treatment in numerous reconstruction procedures at present. Different reasons and varying degress of the laryngotracheal defect bring about huge difficult for clinical therapy. Researchs of repair and reconstruction of laryngotracheal defect have paid mainly attention to option and process,as well as to pattern of reconstruction for a long time. Recently some researchers have studied various of repair material and reconstruction method of longer tracheal defect through animal model,and have found that vascularization and epithelialization of the prosthesis remains a challenge problem for the otolaryngologist. However, There are still no reports on the novel meta-stableβ-type titanium (TLM )alloy prosthesis for replacement of larynx and tracheal defect.Objective: To explore and evaluate the efficacy of the larynx and tracheal reconstruction via in TLM in a canine model, to provide a selectable material for the treatment of laryngotracheal defect. And to provide evidences for the clinical therapy for the reconstruction method of laryngotracheal defect.Methods : 1. It was made by cutting a TLM2 alloy plate and drilling tiny holes with laser on it. Rat NIH-3T3 cells were plated at a density of 1×105cells/ml on porous TLM samples placed in 6-well plastic plates after high pressure sterilization. Then they were cultured for 4 hours .The material was scaned by an electron microscope. The microscopic photos were analyzed by image pattern analysis to measure the porous size and porous rate.The cells on the samples surface were observed to assess its activit and shape. 2. Porous TLM alloy was used as a tissue scaffold for airway regeneration in five dogs. the larynx and the trachea were exposed. The anterior 1/3 part of the cricoid cartilage (cover the cricothyroid membrane) and 1 cervical trachea were simultaneously resected by cold instruments form an artificial anterior larynx open. The"◇"scaffold material was implanted into the resultant defect. Endoscopic examination was undertaken periodically for a postoperative period of 3 to 6 months in all dogs.3. A porous type of cricotracheal prosthesis made of porous TLM alloy is designed. This prosthesis (20 mm in length) is used to reconstruct the cricoid cartilage and the first tracheal ring in 10 mongrel dogs and its efficacy is evaluated. 4. Twenty adult mongrel dogs were chosen , divided randomly two groups. The TLM prosthesis were implanted into one group of dogs(n=10),and the pure titanium(Ti-2) prosthesis were implanted into another group of dogs(n=10). Cricoid cartilage and the first 1,2 tracheal ring reconstruction was performed with the biomedical materials both the TLM and the Ti-2 prosthesis (25 mm in length) in dogs. All dogs were euthanized in 1, 4 and 12 weeks and tracheal CT scan, tracheal endoscopy,histopathological examination and scanning electron microscopic examinations were performed. 5. 5 cm long segment of the cervical trachea was resected in 5 dogs. Porous TLM is fabricated into the shape of a human trachea to repair circumferential tracheal defects. The planned period for the implantation was from3 to 8 months before the sacrifice of the animals for endoscopic examination, CT scan and histological analysis.Results: 1. Scanning electron microscopic photos showed that the surface structure of the samples was porous and the diameters varied from 70 to 90μm.The image analysis demonstrated that the porous rate was 32%. Cells appeared to have a normal cellular shape with lamellipodia and pseudopodia. 2. Endoscopic examination showed the implant located perfectly and the airway is wide enough for breath. There was no airway stenosis in any of the dogs. Granulation was observed in no cases, and anastomotic dehiscence was not observed. 3. One dog died due to an accident with anesthesia at 1 week, one dog died of pneumonia about 1 month after operation,and six dogs were killed between 3 and 8 months; At sacrifice, all the prostheses had become completely incorporated into the host tissue. Endoscopic examination showed no airway obstruction for a postoperative period of 3 to 8 months in 8 dogs. Granulation was observed in 4 cases, and the porous TLM alloy plate was exposed in 1 case, but these dogs were asymptomatic. Light microscopy and electron microscopy showed a normal mucous membrane growth on the prosthesis surface and no visible granulation tissue in the reconstructed cricoid and tracheal cavity. 4. Two type of the biomedical materials showed excellent mechanical strength after implantation. the Porous TLM alloy prothesis was present air-tightness after implantation at early period. The CT scan,endoscopic examination showed no apparent airway obstruction for a postoperative period of 1 to 12 weeks in TLM group,only 3 cases was free of airway obstruction in Ti-2 group. Histologic result showed a normal mucous membrane with normal cilial growth on the TLM implant.5. The mechanical performance of the prostheses was good and the protheses were integrated by the surrounding tissue.Results showed an adequate consistency of prosthesis, adequate tolerance without producing tracheal stenoses, and impermeability to air, allowing a correct invasion by granulation tissue. Conclusion : 1. For the first time, we conclude that this TLM alloy is a kind of excellent biomedical material in replacement of larynx and tracheal defect due to its traits as having moderate strength,toughness matching,low elastic modulus(30～50Gpa),corrosion resistance,which provide a good stress distribution for reconstruction of laryngotracheal defect. 2. For the first time, It was made by cutting a TLM alloy plate and drilling tiny holes with laser on it. The diameter of the porosities was 70~90μm,giving a porosity of 30~35%, thickness was 0.5mm.We found that good incorporation of the prosthesis pore into the host tissue to maintain the air-tightness of the prosthesis after implantation in the early period,and confluent regeneration of the epithelium over the TLM alloy to overcome stenosis of prosthesis lumen. This process was faster than any found in any other porous tracheal prosthesis so far tested. We further proved that epithelialization results from capillary invasion through the prosthetic pores and growth from both tracheal ends.3. The TLM alloy is a potential new biomaterial for laryngotracheal defect reconstruction,which has highly research value for clinical application in the future.