Hybrid nanocomposite as a chest wall graft with improved vascularization by copper oxide nanoparticles

Abstract

Chest wall repair can be necessary after tumor resection or chest injury. In order to cover or replace chest wall defects, autologous tissue or different synthetic materials are commonly used, among them the semi-rigid gold standard Gore-Tex® and prolene meshes. Synthetic tissues include composite materials with an organic and an inorganic component. On the basis of previously reported hybrid nanocomposite poly-lactic-co-glycolic acid amorphous calcium phosphate nanocomposite (PLGA/aCaP), a CuO component was incorporated to yield (60%/35%/5%). This graft was tested in vitro by seeding with murine adipose-derived stem cells (ASCs) for cell attachment and migration. The graft was compared to PLGA/CaCO$_{3}$ and PLGA/hydroxyapatite, each providing the inorganic phase as nanoparticles. Further characterization of the graft was performed using scanning electron microscopy. Furthermore, PLGA/aCaP/CuO was implanted as a chest wall graft in mice. After 4 weeks, total cell density, graft integration, extracellular matrix components such as fibronectin and collagen I, the cellular inflammatory response (macrophages, F4/80 and lymphocytes, CD3) as well as vascularization (CD31) were quantitatively assessed. The nanocomposite PLGA/aCaP/CuO showed a good cell attachment and cells migrated well into the pores of the electrospun meshes. Cell densities did not differ between PLGA/aCaP/CuO and PLGA/CaCO$_{3}$ or PLGA/hydroxyapatite, respectively. When applied as a chest wall graft, adequate stability for suturing into the thoracic wall could be achieved. Four weeks post-implantation, there was an excellent tissue integration without relevant fibrotic changes and a predominating collagen I matrix deposition within the graft. Slightly increased inflammation, reflected by increased infiltration of macrophages could be observed. Vascularization of the graft was significantly enhanced when compared with PLGA/aCaP (no CuO). We conclude that the hybrid nanocomposite PLGA/aCaP/CuO is a viable option to be used as a chest wall graft. Surgical implantation of the material is feasible and provides stability and enough flexibility. Proper tissue integration and an excellent vascularization are characteristics of this biodegradable material.