title: 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.
authors.affiliation: Tissue Regeneration and Molecular Cell Engineering Lab, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Gupta
authors.forename: Goo-Hyun
authors.initials: GH
authors.lastname: Mun
authors.forename: Bina
authors.initials: B
authors.lastname: Choi
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseh
authors.forename: Lopez
authors.initials: L
authors.lastname: Mildred
authors.forename: Anish
authors.initials: A
authors.lastname: Patel
authors.forename: Qixu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Janet E
authors.initials: JE
authors.lastname: Price
authors.forename: David
authors.initials: D
authors.lastname: Chang
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Robb
authors.forename: Anshu B
authors.initials: AB
authors.lastname: Mathur
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage*; D004642:Emodin / Q000494:pharmacology; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D051381:Rats; D011923:Rats, Nude; D047011:Silk / Q000008:administration & dosage*; D013524:Surgical Flaps; D013718:Tensile Strength; D054457:Tissue Scaffolds; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D047011:Silk; D048271:Chitosan; D004642:Emodin