Is it equivalent? Evaluation of the clinical activity of single agent Lipodox® compared to single agent Doxil® in ovarian cancer treatment.

BACKGROUND: In response to the critical shortage of liposomal doxorubicin (Doxil®) in the United States, the Food and Drug Administration (FDA) approved temporary importation of doxorubicin hydrochloride liposome (Lipodox®). The objective was to compare toxicity and clinical activity of Lipodox® with Doxil®. METHODS: Recurrent ovarian cancer patients who received Lipodox® were compared 3:1 to matched control Doxil® patients who had received Doxil®. Patients were matched based on age, stage, dose, platinum sensitivity, and prior treatments from an existing de-identified database. Patients receiving combination regimens were excluded. RESULTS: The data from 40 Lipodox® patients was compared to 120 matched control Doxil® patients. In this study, 17 (42.5%) of the Lipodox® patients were switched to Doxil®. The overall response rate Lipodox® was 4.3% (1/23) compared to 18% (20/111) in matched control Doxil® patients. In the platinum-sensitive patients, 100% progressed in the Lipodox® group compared to 78.4% in matched control Doxil® patients. The mean time to progression was 4.1 ± 2.8 months for Lipodox® and 6.2 ± 7.2 months in control Doxil®s (p = 0·25). Toxicity was similar in the Lipodox® group and control Doxil® group. CONCLUSION: Lipodox® for treatment of recurrent ovarian cancer did not appear to have equivalent efficacy compared to Doxil®. A prospective clinical study is warranted before Lipodox® can be deemed equivalent substitution for Doxil®.

Perichondrium directed cartilage formation in silk fibroin and chitosan blend scaffolds for tracheal transplantation.

The purpose of this study was to investigate the potential of silk fibroin and chitosan blend (SFCS) biological scaffolds for the purpose of cartilage tissue engineering with applications in tracheal tissue reconstruction. The capability of these scaffolds as cell carrier systems for chondrocytes was determined in vitro and cartilage generation in vivo on engineered chondrocyte-scaffold constructs with and without a perichondrium wrapping was tested in an in vivo nude mouse model. SFCS scaffolds supported chondrocyte adhesion, proliferation, and differentiation, determined as features of the cells based on the spherical cell morphology, increased accumulation of glycosaminoglycans, and increased collagen type II deposition with time within the scaffold framework. Perichondrium wrapping significantly (P<0.001) improved chondrogenesis within the cell-scaffold constructs in vivo. In vivo implantation for 6weeks did not generate cartilage structures resembling native trachea, although cartilage-like structures were present. The mechanical properties of the regenerated tissue increased due to the deposition of chondrogenic matrix within the SFCS scaffold structural framework of the trachea. The support of chondrogenesis by the SFCS tubular scaffold construct resulted in a mechanically sound structure and thus is a step towards an engineered trachea that could potentially support the growth of an epithelial lining resulting in a tracheal transplant with properties resembling those of the fully functional native trachea.

Comparison of cross-linked and non-cross-linked porcine acellular dermal matrices for ventral hernia repair.

BACKGROUND: Porcine acellular dermal matrices (PADMs) have been used clinically for abdominal wall repair. The newer non-cross-linked PADMs, however, have not been directly compared with cross-linked PADMs. We hypothesized that chemical cross-linking affects the biologic host response to PADMs used to repair ventral hernias. STUDY DESIGN: Fifty-eight guinea pigs underwent inlay repair of surgically created ventral hernias using cross-linked or non-cross-linked PADM. After animals were sacrificed at 1, 2, or 4 weeks, the tenacity of and surface area involved by adhesions to the repair sites were measured. Sections of the repair sites, including the bioprosthesis-musculofascia interface, underwent histologic analysis of cellular and vascular infiltration plus mechanical testing. RESULTS: Compared with cross-linked PADM repairs, non-cross-linked PADM repairs had a significantly lower mean tenacity grade of adhesions at all timepoints and mean adhesion surface area at week 1. Mean cellular and vascular densities were significantly higher in non-cross-linked PADM at all timepoints. Cells and vessels readily infiltrated into the center of non-cross-linked PADM, but encapsulated cross-linked PADM, with a paucity of penetration into it. Mechanical properties were similar for the two PADMs (in isolation) at all timepoints; however, at the bioprosthesis-musculofascia interface, both elastic modulus and ultimate tensile strength were significantly higher at weeks 1 and 2 for non-cross-linked PADM. CONCLUSIONS: Non-cross-linked PADM is rapidly infiltrated with host cells and vessels; cross-linked PADM becomes encapsulated. Non-cross-linked PADM causes weaker adhesions to repair sites while increasing the mechanical strength of the bioprosthesis-musculofascia interface at early timepoints. Non-cross-linked PADM may have early clinical advantages over cross-linked PADM for bioprosthetic abdominal wall reconstruction.

Non-cross-linked porcine acellular dermal matrices for abdominal wall reconstruction.

BACKGROUND: Non-cross-linked porcine acellular dermal matrices have been used clinically for abdominal wall repair; however, their biologic and mechanical properties and propensity to form visceral adhesions have not been studied. The authors hypothesized that their use would result in fewer, weaker visceral adhesions than polypropylene mesh when used to repair ventral hernias and form a strong interface with the surrounding musculofascia. METHODS: Thirty-four guinea pigs underwent inlay repair of surgically created ventral hernias using polypropylene mesh, porcine acellular dermal matrix, or a composite of the two. The animals were killed at 4 weeks, and the adhesion tenacity grade and surface area of the repair site involved by adhesions were measured. Sections of the repair sites, including the implant-musculofascia interface, underwent histologic analysis and uniaxial mechanical testing. RESULTS: The incidence of bowel adhesions to the repair site was significantly lower with the dermal matrix (8 percent, p < 0.01) and the matrix/mesh combination (0 percent, p < 0.001) than with polypropylene mesh alone (70 percent). The repairs made with the matrix or the matrix/mesh combination, compared with the polypropylene mesh repairs, had significantly lower mean adhesion surface areas [12.8 percent (p < 0.001), 9.2 percent (p < 0.001), and 79.9 percent] and grades [0.6 (p < 0.001), 0.6 (p < 0.001), and 2.9]. The dermal matrix underwent robust cellular and vascular infiltration. The ultimate tensile strength at the implant-musculofascia interface was similar in all groups. CONCLUSIONS: Porcine acellular dermal matrix becomes incorporated into the host tissue and causes fewer adhesions to repair sites than does polypropylene mesh, with similar implant-musculofascia interface strength. It also inhibits adhesions to adjacent dermal matrix in the combination repairs. It has distinct advantages over polypropylene mesh for complex abdominal wall repairs, particularly when material placement directly over bowel is unavoidable.

Fabrication and characterization of silk-fibroin-coated quantum dots.

We report a novel technique of directly coating colloidal CdSe/ZnS core/shell quantum dots (QDs) with silk fibroin (SF), a protein derived from the Bombyx mori silk worm. The approach results in protein-modified QDs with little or no particle aggregation, and mitigates the issue of biocompatibility. QDs have desirable optical properties, such as narrow-band emission, broadband absorption, high quantum yield, and high resistance to photobleaching. SF is a fibrous protein polymer with a biomimetic peptide sequence, water and oxygen permeability, low inflammatory response, no thrombogenecity, and cellular biocompatibility, which are desirable properties for in vivo delivery. Combining the unique properties of QDs with the biocompatibility profile of SF, the approach produces particles representing a powerful tool for numerous in vivo and in vitro applications. The design and preparation of these protein-modified QDs conjugates is reported along with functional characterization using luminescence, transmission electron microscope (TEM), and atomic force microscope (AFM). Additionally, we report results obtained using the QDs conjugates as a fluorescent label for bioimaging HEYA8 ovarian cancer cells.