Stiffness-matched biomaterial implants for cell delivery: clinical, intraoperative ultrasound elastography provides a ‘target’ stiffness for hydrogel synthesis in spinal cord injury

Safe hydrogel delivery requires stiffness-matching with host tissues to avoid iatrogenic damage and reduce inflammatory reactions. Hydrogel-encapsulated cell delivery is a promising combinatorial approach to spinal cord injury therapy, but a lack of in vivo clinical spinal cord injury stiffness measurements is a barrier to their use in clinics. We demonstrate that ultrasound elastography – a non-invasive, clinically established tool – can be used to measure spinal cord stiffness intraoperatively in canines with spontaneous spinal cord injury. In line with recent experimental reports, our data show that injured spinal cord has lower stiffness than uninjured cord. We show that the stiffness of hydrogels encapsulating a clinically relevant transplant population (olfactory ensheathing cells) can also be measured by ultrasound elastography, enabling synthesis of hydrogels with comparable stiffness to canine spinal cord injury. We therefore demonstrate proof-of-principle of a novel approach to stiffness-matching hydrogel-olfactory ensheathing cell implants to ‘real-life’ spinal cord injury values; an approach applicable to multiple biomaterial implants for regenerative therapies

Growth capacity of a Wharton’s Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets

Background: Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton’s Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy.Methods: Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry.Results: Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded.Conclusion: Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT

Evaluation of a novel atrial retractor for exposure of the mitral valve in a porcine model

ObjectivesTo describe a novel atrial retractor and compare 2 methods of intraoperative left atrial retraction for minimally invasive mitral valve repair.MethodsLeft atrial retraction was performed on 5 swine cadavers to evaluate performance (percent of mitral valve annulus accessible), complications encountered, ease of use, and surgical time for the minimally invasive atrial retractor and a HeartPort atrial retractor.ResultsEstimated accessibilities were 93.0% (standard error = 3.2) and 92.7% (standard error = 3.3) for the HeartPort and minimally invasive atrial retractor retractors, respectively, with a difference of 0.3% (standard error = 2.2%, P = .8832, df = 34). Tissue damage occurred in 1 case for the minimally invasive atrial retractor and 2 cases for the HeartPort retractor. The mean surgical times for retractor placement and mitral valve annulus exposure were 107.4 and 39.2 seconds for the HeartPort and minimally invasive atrial retractor retractors, respectively, with a difference of 68.2 seconds (P = .0092, df = 4).ConclusionsThe minimally invasive atrial retractor is a suitable alternative for atrial retraction compared with standard techniques of retraction. It provides comparable exposure of the mitral valve annulus, is less time consuming to place, provides subjectively more working volume within the left atrium, and has the advantage of minimal atriotomy incision length and customizable retraction