Developing a synthetic composite membrane for cleft palate repair

Abstract

An oronasal fistula is a passage between the oral and nasal cavity. Currently, surgical procedures use mucosal flaps or collagen grafts to make a barrier between oral and nasal cavities. Our aim was to develop a cell-free synthetic repair material for closure of nasal fistulas. We surface functionalized electrospun polyurethane (PU) and poly-Llactic acid (PLLA) and composite polymer (PU-PLLA) membranes with acrylic acid through plasma polymerization. Membranes were treated in a layer-by-layer approach to develop highly charged electrostatic layer that could bind heparin as a pro-angiogenic glycosaminoglycan. The properties were evaluated through physical, chemical, and mechanical characterization techniques. Cytotoxicity was tested with MC3T3 pre-osteoblast cell lines for 3, 7, and 14 days, and vasculogenesis was assessed by implantation into the chorio-allantoic membrane in chick embryos for 7 days. In vivo biocompatibility was assessed by subcutaneous implantation in rats for 1, 3, and 6 weeks. The membranes consisted of random fibers of PLLA-PU with fiber diameters of 0.47 and 0.12 μm, respectively. Significantly higher cell proliferation and migration of MC3T3 cells at 3, 7, and 14 days were shown on plasmacoated membranes compared with uncoated membranes. Further, it was found that plasma-coated membranes were more angiogenic than controls. In vivo implantation of membranes in rats did not reveal any gross toxicity to the materials, and wound healing was comparable with the native tissue repair (sham group). We therefore present a plasma-functionalized electrospun composite polymer membrane for use in the treatment of fistulas. These membranes are flexible, non-cytotoxic, and angiogenic, and we hope it should lead to permanent closure of oronasal fistula.

Application of tissue engineering in paediatric

“…La fisura labiopalatina es la malformación congénita craneofacial más frecuente, con una incidencia aproximada de uno por cada 700 recién nacidos vivos (4,40,41). Actualmente, el manejo estándar es el cierre quirúrgico del defecto, tratándose de intervenciones complejas en las que no solo se persigue el cierre del paladar sino la corrección y/o prevención de problemas a menudo asociados de dicción, oclusión dentaria, otitis crónicas y déficits óseos maxilares (4).…”

“…La ingeniería tisular se basa en la utilización de biomateriales o scaffolds en los que hacer proliferar las poblaciones celulares. Estos scaffolds deben ser biocompatibles, proporcionando un ambiente ideal para la interacción celular, proliferación, migración celular, diferenciación y al mismo tiempo, tener la capacidad de degradarse una vez lograda su función sin generar productos de desecho que se puedan acumular e interferir en el proceso regenerativo (3,4). Podemos encontrar scaffolds sintéticos, constituidos por polímeros biodegradables (policapronolactona, polietilen-glicol, ácido poliglicólico…), y naturales derivados de matrices extracelulares, hechos a base de proteínas como el colágeno, fibrina, agarosa o la laminina, o a partir de tejidos animales descelularizados.…”

Tissue Engineering in Stomatology: A Review of Potential Approaches for Oral Disease Treatments

“…Sharif et al developed a plasma-functionalized electrospun composite polymer membrane, modified the fabricated membranes by plasma polymerization, and then implanted them in rats subcutaneously. The results showed that these membranes were biocompatible and angiogenic, providing the possibility for permanent closure of oronasal fistula ( Sharif et al, 2019 ). Lee et al created cell sheets derived from hMSCs and SHEDs for bone repair of cleft palate and found that the cell sheets led to calcification in vitro , which indicated that osteogenic stem cell sheets may become a new choice for the reconstruction of cleft palate ( Lee J.-M. et al, 2019 ).…”

Effect of collagen matrix on postoperative palatal fistula in cleft palate repair

“…There are numerous techniques to prevent and treat postoperative palatal fistula using local or distant tissues 5,[7][8][9][10][11][12] . Attempts have also been made to develop synthetic biomaterials that can decrease the incidence of postoperative fistula 13 . There are several recent reports of favorable outcomes after the use of acellular dermal matrix (ADM) 4,5,14,15 .…”