Effect of Functionalization of Texturized Polypropylene Surface by Silanization and HBII-RGD Attachment on Response of Primary Abdominal and Vaginal Fibroblasts.

Soft tissue defects, such as incisional hernia or pelvic organ prolapse, are prevalent pathologies characterized by a tissue microenvironment rich in fragile and dysfunctional fibroblasts. Precision medicine could improve their surgical repair, currently based on polymeric materials. Nonetheless, biomaterial-triggered interventions need first a better understanding of the cell-material interfaces that truly consider the patients' biology. Few tools are available to study the interactions between polymers and dysfunctional soft tissue cells in vitro. Here, we propose polypropylene (PP) as a matrix to create microscale surfaces w/wo functionalization with an HBII-RGD molecule, a fibronectin fragment modified to include an RGD sequence for promoting cell attachment and differentiation. Metal mold surfaces were roughened by shot blasting with aluminum oxide, and polypropylene plates were obtained by injection molding. HBII-RGD was covalently attached by silanization. As a proof of concept, primary abdominal and vaginal wall fasciae fibroblasts from control patients were grown on the new surfaces. Tissue-specific significant differences in cell morphology, early adhesion and cytoskeletal structure were observed. Roughness and biofunctionalization parameters exerted unique and combinatorial effects that need further investigation. We conclude that the proposed model is effective and provides a new framework to inform the design of smart materials for the treatment of clinically compromised tissues.

Preventive midline laparotomy closure with a new bioabsorbable mesh: an experimental study.

BACKGROUND: Incisional hernia formation is one of the most frequent complications of midline laparotomies requiring reoperation. The aim of this study was to evaluate the safety and efficacy of prophylactically placing a biodegradable mesh within the incision site at closure in a rat model. METHODS: A 4-cm full-thick midline laparotomy was made in Sprague-Dawley rats along the linea alba and closed by inserting a commercially available web of synthetic polymers (polyglycolic acid-trimethylene carbonate) that are slowly degraded by the body. Host tissue reaction was evaluated ex vivo and compared with that obtained in suture-only-treated rats. Specimens were harvested at 1, 3, and 6mo after surgery and divided for histologic and zymographic analyses and uniaxial material testing. A group of intact nonoperated animals were included to serve as a reference. RESULTS: The excised tissue explants revealed that the performance of the synthetic device was good and resulted in enhanced fibroproliferation, gelatinolytic activity, and angiogenesis within the repair site as compared with the suture-only procedure. Lastly, tensile strength augmented over the suture-only condition. CONCLUSIONS: The preventive introduction of an absorbable mesh stimulates new tissue ingrowth and performance relative to suture repair without prosthesis, probably contributing to eventually reinforce the tension line. These results have a clinical potential in abdominal wall closure, especially in patients with multiple risk factors such as those treated for aortic reconstructive surgery, without the short- and long-term complications related to permanent grafts. However, data are preliminary and should be confirmed with longer follow-ups.

Mutations in LOXHD1, an evolutionarily conserved stereociliary protein, disrupt hair cell function in mice and cause progressive hearing loss in humans.

Hearing loss is the most common form of sensory impairment in humans and is frequently progressive in nature. Here we link a previously uncharacterized gene to hearing impairment in mice and humans. We show that hearing loss in the ethylnitrosourea (ENU)-induced samba mouse line is caused by a mutation in Loxhd1. LOXHD1 consists entirely of PLAT (polycystin/lipoxygenase/alpha-toxin) domains and is expressed along the membrane of mature hair cell stereocilia. Stereociliary development is unaffected in samba mice, but hair cell function is perturbed and hair cells eventually degenerate. Based on the studies in mice, we screened DNA from human families segregating deafness and identified a mutation in LOXHD1, which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). LOXHD1, MYO3a, and PJVK are the only human genes to date linked to progressive ARNSHL. These three genes are required for hair cell function, suggesting that age-dependent hair cell failure is a common mechanism for progressive ARNSHL.