Abstract
Surgery of the chest wall is potentially required to cover large defects after removal of malignant tumours. Usually, inert and non-degradable Gore-Tex serves to replace the missing tissue. However, novel biodegradable materials combined with stem cells are available that stimulate the healing. Based on poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/aCaP) and pure PLGA, a dual layer biodegradable hybrid nanocomposite was generated. Mouse adipose-derived stem cells were cultered on electrospun disks (ASCs of C57BL/6), and biomechanical tests were performed. The cell-seeded scaffolds were engrafted in C57BL/LY5.1 mice to serve as a chest wall substitute. Cell invasion into the bi-layered material, extent of CD45+ cells, inflammatory response, neo-vascularization and ECM composition were determined at 1 and 2 months post-surgery, respectively. The bi-layered hybrid nanocomposite was stable after a 2-week in vitro culture, in contrast to PLGA/aCaP without a PLGA layer. There was a complete biointegration and good vascularization in vivo. The presence of ASCs attracted more CD45+ cells (hematopoietic origin) compared to cell-free scaffolds. Inflammatory reaction was similar for both groups (±ASCs) at 8 weeks. A bi-layered hybrid nanocomposite fabricated of electrospun PLGA/aCaP and a reinforcing layer of pristine PLGA is an ideal scaffold for chest wall reconstruction. It is stable and allows a proper host tissue integration. If ASCs are seeded, they attract more CD45+ cells, supporting the regeneration process.
Highlights
Many chest wall discontinuities follow from the removal of aggressive tumors[1,2], needing adequate covering and chest wall reconstruction[3]
While pure PLGA had the highest failure stress, followed by the hybrid mesh, both being significantly higher than pure PLGA/aCaP mesh, a 2-week incubation in DMEM lowered the maximum strength for all three scaffold materials; in case of PLGA and hybrid scaffold only to a minor extent
Our research team has demonstrated that cells infiltrate better into a porous electrospun PLGA/ aCaP nanocomposite used as a chest wall graft in mice compared to the non-porous inert Gore-Tex material that is currently used as a gold standard[27]
Summary
Many chest wall discontinuities follow from the removal of aggressive tumors[1,2], needing adequate covering and chest wall reconstruction[3]. Biomaterials offer a viable option – either synthetic[10,11] or natural like cellulose[12], among others[13,14] Synthetic materials, such as prolene, polypropylene meshes or Gore-Tex, are utilized for chest wall reconstruction in daily clinical practice[15], in combination with perforator flaps[16] or small intestinal submucosa, a natural product that is made cell-free before application[14,17]. ASCs are harvested, prevailing in abundance[28] and adequate proliferation and migration into electrospun meshes composed of PLGA/aCaP has been shown[29,30] They represent an ideal stem cell source to seed a chest wall construct
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