Thomas W. Gilbert

The extracellular matrix (ECM) is composed of a complex mixture of structural and functional macromolecules that are important during growth, development, and wound repair. In this study, we seek to determine if an ECM derived from the porcine urinary bladder, specifically urinary bladder matrix (UBM), can act to prevent bacterial infection in the context of lung injury. In this study, we examined a digested form of UBM, which prevented bacterial biofilm formed by both Gram-positive bacteria (GPB) such as methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) and Gram-negative bacteria (GNB), including Pseudomonas aeruginosa (PA) and Klebsiella pneumoniae (KP) in vitro . Furthermore, exogenously administered UBM digest exhibited host protection from MSSA-, MRSA-, and PA-induced respiratory infection in a murine infection model. The protection against both GPB- and GNB-induced infection demonstrated by UBM suggests the antibacterial function is likely through biofilm prevention. In addition, two potential off the shelf UBM product forms (preformulated digested UBM and intact UBM particulate) showed significant protection from acute severe respiratory infection. Taken together, our results support further study of the use of UBM as an alternative treatment to attenuate bacterial-induced infection. Impact Statement: Lung infection is a leading cause of human life lost to morbidity and/or mortality. This problem is exacerbated by the alarming emergence of increasingly antibiotic-resistant (AR) microorganisms worldwide and the lack of effective antimicrobials to overcome the AR bacterial infection. Urinary bladder matrix (UBM) is a biologically derived scaffold material that has been used to promote site-appropriate tissue regeneration and remodeling in a variety of body systems. Our novel findings demonstrate that the preformulated UBM effectively protects the host from methicillin-resistant Staphylococcus aureus (MRSA)- and Pseudomonas aeruginosa -induced murine pneumonia and may provide a viable alternative/supplement for protection against respiratory AR bacterial infection.

Tracheal stenting currently using non‐degradable stents is commonplace for treatment of trauma, prolonged intubation related adult airway obstructions, and pediatric patients‐associated tracheal stenosis conditions. Degradable tracheal stent placement will avoid complications of stent removal and restenosis. Widespread reports exist on degradable magnesium alloys success for orthopedic and cardiovascular applications but none to date for intra tracheal use. This research explores the use of pure Mg, AZ31, and Mg‐3Y alloys for degradable tracheal stent assessment. In vitro evaluation of magnesium, prototype stents in a bioreactor simulate the airway environment and corrosion. Micro‐CT imaging and biocompatibility evaluation helped assess the 24‐week degradation of intraluminal alloy stents following implantation in a rat tracheal in vivo bypass model. Histological analysis indicate tissue response of the harvested stented trachea segments after each time point. Corrosion studies for each alloy indicate significant differences between the simulated and control in vitro conditions. AZ31 exhibited the lowest volume loss of 6.8% in saline, while pure Mg displayed the lowest volume loss of 4.6% in simulated airway fluid (SAF), both at 1‐week time points. Significant differences in percentage of total volume lost after 6 months were determined between the alloys over time. MgY alloy displayed the slowest corrosion losing only 15.1% volume after 24 weeks of immersion. Additionally, in vitro magnesium alloy corrosion was not significantly different from the percentage of total volume lost in vivo at 1‐week time point. The study demonstrates promise of magnesium alloys for intraluminal tracheal stent application albeit viability of a clinically translatable model warrants further studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1844–1853, 2019.

Biologically derived surgical graft materials come from a variety of sources with varying mechanical properties. This study aimed to evaluate the host response and mechanical performance of two extracellular matrix devices in a large animal preclinical model. Bilateral defects were created in the fascia lata of sheep and repaired with either an acellular dermal matrix (ADM) or urinary bladder matrix (UBM). After 1 or 3 months, the repair site was explanted for histological and mechanical analysis. Despite pre-implantation mechanical differences, both UBM and ADM demonstrated similar mechanical performance at 3 months. However, UBM was completely remodeled into site-appropriate tissue by 3 months, while ADM showed limited tissue incorporation.

Aim: Not all biologically derived materials elicit the same host response when used for reinforcement of ventral hernia repairs. This study aimed to evaluate the remodeling characteristics of the abdominal wall following reinforcement with urinary bladder matrix (UBM) in a large animal preclinical model of ventral hernia repair. Materials & methods: Midline defects in 36 Yucatan minipigs were reinforced with UBM-derived surgical devices using a classic Rives–Stoppa–Wantz approach, and compared with primary repair controls. After 3 or 8 months, the abdominal wall was explanted for histological and mechanical analysis. Results & conclusion: All UBM-derived surgical devices were completely resorbed within 8 months and facilitated deposition of vascularized, biomechanically functional connective tissue in the retrorectus plane, with no evidence of hernia formation.

The objective of this prospective, multicentre clinical study is to assess the application of MatriStem MicroMatrix (MSMM) and MatriStem Wound Matrix (MSWM) (porcine urinary bladder derived extracellular matrix) compared with Dermagraft (DG) (human fibroblast-derived dermal substitute) for the management of non-healing diabetic foot ulcers (DFUs).

Tracheal loss is a source of significant morbidity for affected patients with no acceptable solution. Interest in engineering tracheal transplants has created a demand for small animal models of orthotopic tracheal transplantation. Here, we examine the use of a decellularized graft in a murine model of tracheal replacement. Fresh or decellularized tracheas harvested from age-matched female donor C57BL/6 mice were transplanted into syngeneic recipients. Tracheas were decellularized using repeated washes of water, 3% Triton X-100, and 3 M NaCl under cyclic pressure changes, followed by disinfection with 0.1% peracetic acid/4% ethanol, and terminal sterilization by gamma irradiation. Tracheas were explanted for immunolabeling at 1, 4, and 8 weeks following surgery. Video microscopy and computed tomography were performed to assess function and structure. Decellularized grafts supported complete reepithelialization by 8 weeks and motile cilia were observed. Cartilaginous portions of the trachea were maintained in mice receiving fresh transplants, but repopulation of the cartilage was not seen in mice receiving decellularized transplants. We observed superior postsurgical survival, weight gain, and ciliary function in mice receiving fresh transplants compared with those receiving decellularized transplants. The murine orthotopic tracheal transplant provides an appropriate model to assess the repopulation and functional regeneration of decellularized tracheal grafts.