Tissue Remodeling in a Bioartifical Fibromuscular Patch Following Transplantation in a Human

Abstract

Tissue engineering applications might help to overcome currently encountered limitations in reconstructive surgery in many surgical subspecialties (1). Recently we reported the successful reconstruction of a tracheobronchial defect in a patient using a bioartificial airway patch (2). Here we describe the remodeling of the transplanted bioartificial tissue. In a 58-year-old male, a bioartificial fibromuscular patch was implanted into a 1.5 × 1.5 cm large tracheobronchial anastomosis defect (onset 4 weeks postoperatively) as previously described in detail (2). Briefly, the patient had undergone right carinal pneumectomy for relapsing non–small-cell lung cancer following operation and radiation (60 Gy) 4 years earlier. The defect had caused pleural empyema and pyosepticemia which were treated by thoracostomy and medically. At time of patch implantation, an omentum major transposition and right subscapular myoplasty combined with a thoracoplasty were performed. The patch had been generated within 5 weeks from a 3 × 4 cm skin biopsy that was obtained at the thoracostomy site. Autologous muscle cells (MC) and fibroblasts (Fb) were isolated enzymatically from the biopsy and cultured for 2 weeks (37°C, HAM-F12/MEM culture media; volume ratio 50:50). An acellular 24 × 36 mm collagen network (derived from a porcine jejunal segment) served as carrier matrix. Autologous Fb and MC in a cell ratio of 95:5 were seeded for 3 weeks on the matrix (37°C, HAM-F12/MEM culture media; volume ratio 50:50). Patch integrity was controlled by fibroscopies 1, 3, 6, and 12 weeks following implantation. We detected patch matrix reorganization resulting in increased mechanical stability and a defect area decrease from 12 × 9 mm to 9 × 5 mm. A transtracheal patch biopsy performed 12 weeks after implantation documented a harmonic cellular distribution pattern with a surprisingly altered patch composition representing 80% MC and 20% Fb (Fig. 1).FIGURE 1.: Cellular patch composition. Overall cell number doubled within 3 months. Fb represented the cellular majority during tissue culture before implantation (in vitro). Three months after implantation tissue remodeling resulted in a dominant MC fraction.Numerous clinical and experimental studies surveyed bioartificial implants for a wide range of clinical applications, including tracheal reconstruction (1). As yet, the venture to generate a bioartificial tracheal substitute did not provide a convincing graft (3) and currently autologous repair tissues (i.e., pericardial patches) represent dependable alternatives for limited tracheal reconstruction that result in scar tissue formation and contraction of the airway defect (4). In our presented case, we repaired a limited defect in the tracheobronchial system with a tissue engineered autologous tracheal patch. Analogous to clinical experiences with autologous pericardial patches, we detected a decrease of defect size over time. In contrast to previous findings, patch biopsy revealed a profound change of tissue composition within the first 3 months following implantation: the MC:Fb cell ratio had reversed in favor of MC. This unexpected increase of smooth muscle cells in the patch matrix cannot be explained by cicatrization. The underlying mechanism, however, remains unknown and cannot be explained by our data. Either the privileged ingrowth of patient MC or a survival benefit of implanted MC could explain these findings. In the light of previous unexpected (sometimes fatal) clinical experiences with bioartificial grafts (5), further studies are needed to address questions regarding the healing behavior and mechanisms of bioartificial implants. Thorsten Walles Christian Biancosino Patrick Zardo Paolo Macchiarini Department of Thoracic and Vascular Surgery Heidehaus Hospital Hannover, Germany Jens Gottlieb Department of Pulmonology Medical School Hannover Hannover, Germany Heike Mertsching Fraunhofer Institute for Interfacial Engineering and Biotechnology Stuttgart, Germany