Current treatments for defects of the gastrointestinal and respiratory tract, such as fistulae and surgical anastomotic dehiscence, often involve complex surgical interventions and endoscopic procedures with the use of synthetic materials, which may lead to complications, prolonged hospitalization, poor outcomes, low quality of life, and death. For these reasons, we began applying regenerative medicine using mesenchymal stem cells derived from autologous adipose tissue, achieving good results [1-3,5] in treating these conditions by promoting the growth and repair of damaged tissue. Still, in cases of larger defects, a structural support is required to facilitate better healing and complete closure of the defect. Thus, we aim to create a 3D bioprinted patient-specific scaffold seeded with the mesenchymal stem cells [4].

Fat tissue harvesting and mechanical emulsification of autologous adipose tissue will yield mesenchymal stem cells, as previously described [1-3]. A 3D bioprinter with dual extruder that allows for simultaneous deposition of materials using cartridges at different temperatures will be used to print component I (mechanically strong material made of PLA/PGA or a combination of these materials) and component II (soft bioink for cell support made of collagen, alginate, or hyaluronic acid or a combination). The composition of components I and II is defined based on mechanical testing outcomes (mechanical resistance and flexibility) and on cell growth enhancement in a 3D environment. 

A 74-year-old man developed pneumaturia during chemotherapy + radiotherapy performed after laparoscopic radical prostatectomy with lymphadenectomy + rectal raffia with colonostomy for prostatic adenocarcinoma (cT4). A CT scan confirmed the clinical suspicion of a rectovesical fistula. Two attempts at trans-anal closure of the fistula were performed without success. A further unsuccessful surgical closure attempt was also performed by an open transvesical approach. As a last resort, a permanent urinary catheter was placed. Our rectoscopy showed a 10-mm fistula located on the anterior wall of the rectum, at 2 cm from the internal anal margin. On the rectal side, the mucosa around the fistula borders was massively fibrotic, because of the chronic inflammation due to several surgical closure attempts and radiotherapy. The patient was scheduled for repeated (4 procedures) endoscopic injection of autologous emulsified adipose tissue stromal vascular fraction (tSVFem). Each procedure was performed every 2 months, resulting in a progressive reduction of the fistula diameter to 2 mm, with reduced tissue fibrosis and improved tissue vascularity. Again, complete closure of the fistula was not achieved, and the patient continued to complain of symptoms. Then, we planned to implant a customised 3D-bioprinting-based treatment. The 3D scaffold was a blend of polylactic acid (PLA) and polybutylene adipate-co-terephthalate (PBAT), with a slight curvature and two holes for anchoring to the rectal wall. The scaffold was sutured with Apollo Overstitch, and the tSVFem was injected into the scaffold and the submucosal layer at the fistula borders using a 22-Gauge needle. The post-procedural course was uneventful. The rectoscopy performed 14 days later documented complete healing of the fistula with vascularized mucosal overgrowth and complete degradation of the 3D-printed scaffold. At this stage, the urinary catheter was removed, and no fistula-related symptoms or rectal urinary loss were recorded thereafter. Eight months later, the fistula was still completely closed, and the patient had intestinal recanalisation, without complication or recurrence of the fistula

This procedure offers promising advancements in the field of regenerative medicine. It allows tailored, safe, and effective treatments for complex post-surgical defects. Nevertheless, its effectiveness should be confirmed in a larger patient cohort.