Repair and Reconstruction of a Resected Tumor Defect Using a Composite of Tissue Flap–Nanotherapeutic–Silk Fibroin and Chitosan Scaffold

Abstract

A multifaceted strategy using a composite of anti-cancer nanotherapeutic and natural biomaterials silk fibroin (SF) and chitosan (CS) blend scaffolds was investigated for the treatment of a tissue defect post-tumor resection by providing local release of the therapeutic and filling of the defect site with the regenerative bioscaffolds. The scaffold-emodin nanoparticle composites were fabricated and characterized for drug entrapment and release, mechanical strength, and efficacy against GILM2 breast cancer cells in vitro and in vivo in a rat tumor model. Emodin nanoparticles were embedded in SF and SFCS scaffolds and the amount of emodin entrapment was a function of the scaffold composition and emodin loading concentration. In vitro, there was a burst release of emodin from all scaffolds during the first 2 days though it was detected even after 24 days. Increase in emodin concentration in the scaffolds decreased the overall elastic modulus and ultimate tensile strength of the scaffolds. After 6 weeks of in vivo implantation, the cell density (p < 0.05) and percent degradation (p < 0.01) within the remodeled no emodin SFCS scaffold was significantly higher than the emodin loaded SFCS scaffolds, although there was no significant difference in the amount of collagen deposition in the regenerated SFCS scaffold. The presence and release of emodin from the SFCS scaffolds inhibited the integration of SFCS into the adjacent tumor due to the formation of an interfacial barrier of connective tissue that was lacking in emodin-free SFCS scaffolds. While no significant difference in tumor size was observed between the in vivo tested groups, tumors treated with emodin loaded SFCS scaffolds had decreased presence and size and similar regeneration of new tissue as compared to no emodin SFCS scaffolds.

Silk constructs for delivery of musculoskeletal therapeutics

“…Emodin – a rather hydrophobic anthraquinone with anti-cancer potential – delivery from liposomes embedded within SF / chitosan scaffolds resulted in successfully “reduced tumor presence, scaffold degradation, remodeling, and new tissue deposition” [58] when tested for breast cancer therapy using a rat model. This work is relevant for musculoskeletal application, as it may lead to the combination of the demonstrated mechanical and biocompatibility advantages of SF scaffolds as bone filler or for fracture repair and reconstruction [59] as has been demonstrated when seeded with human mesenchymal stem cells [60, 61] or when ectopically grafted periosteum was used as cell source [62] with the opportunity to provide a sustained release of an anti-cancer drug which may be a small molecule such as emodin [58], a biopharmaceutical (feasibility demonstrated for non-cancer therapy [32, 45]) or by means of gene delivery (feasibility demonstrated for non-cancer therapy [63]). Within the musculoskeletal context, the advantages of SF may be particularly valuable in a rare disease affecting the larger joints - pigmented villonodular synovitis (PVNS).…”

Versatility of Chitosan-Based Biomaterials and Their Use as Scaffolds for Tissue Regeneration

“…Moreover, 19.7% of the studies evaluated CS in the regeneration of skin [ 24 , 27 , 29 , 63 – 71 ], 14.7% in nervous tissue [ 30 , 72 – 79 ], 11.5% in cartilage [ 32 , 81 – 84 , 87 , 88 ], and 3.3% in periodontal [ 33 , 90 ] structures. The remaining studies involved regeneration of colorectal [ 26 ], mammary [ 89 ], tympanic membrane [ 31 ], and vascular [ 34 ] tissues (1.6% each).…”

Approximating the double-cut-and-join distance between unsigned genomes

“…Conceptually, our proposed algorithm operates in the same spirit as many previous algorithms for approximating the genomic distance via genome rearrangement operations [1,10,14,15]. However, when we began this work, it was not clear whether the problem of finding a largest collection of edge-disjoint cycles/AA-paths/AB-paths of length two or three can be reduced to a degree-bounded k -set packing problem (rather than a general k -set packing problem).…”