Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration.

Currently, functional treatment of fracture non-unions and bone loss remains a significant challenge in the field of orthopaedic surgery. Tissue engineering of bone has emerged as a new treatment alternative in bone repair and regeneration. Our approach is to combine a polymeric matrix with a cellular vehicle for delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral gene transfer. The objective of this study is to develop an osteoinductive, tissue-engineered bone replacement system by culturing BMP-2-producing cells on an osteoconductive, biodegradable, polymeric-ceramic matrix. The hypothesis is that retroviral gene transfer can be used effectively in combination with a biodegradable matrix to promote bone formation. First, we examined the in vitro attachment and growth of transfected BMP-producing cells on a PLAGA-HA scaffold. Second, the bioactivity of the produced BMP in vitro was evaluated using a mouse model. It was found that the polymer-ceramic scaffold supported BMP-2 production, allowing the attachment and growth of retroviral transfected, BMP-2-producing cells. In vivo, the scaffold successfully functioned as a delivery vehicle for bioactive BMP-2, as it induced heterotopic bone formation in a SCID mouse model.

Regional drug delivery with radiation for the treatment of Ewing's sarcoma. In vitro development of a taxol release system.

Recently, several studies have suggested the radiosensitizing effect of taxol, a microtubular inhibitor. Our overall hypothesis is that a combination of radiation and taxol may demonstrate therapeutic efficacy over doses of either individually. Studies examining taxol use have mostly focused on systemic administration, which can lead to undesired effects. To circumvent these side effects, we propose a locally administered polymeric microsphere delivery system combined with radiation therapy for the treatment of Ewing's sarcoma. The present study focuses on the in vitro ability of taxol when present as a microencapsulated drug delivery system, and delivered locally at the site of the sarcoma/tumor, to block cells in the G2/M phase of the cell cycle and potentially enhance the radiation sensitivity of cells. Using the bioresorbable poly(anhydride-co-imide), poly[pyromellityl-imidoalanine-1,6-bis(carboxy-phenoxy)hexane] (PMA-CPH), and the radiosensitizing agent taxol, a microsphere based delivery system was fabricated. A solvent evaporation technique was used to encapsulate taxol at doses of 1%, 5%, and 10% in PMA-CPH microspheres. Release kinetics studies demonstrated that the total amount of taxol released and the release rate were directly dependent on loading percentage. Taxol's bioactivity and radiosensitizing ability were measured using flow cytometry. Co-culture of Ewing's sarcoma cells with and without taxol-loaded microspheres demonstrated that released taxol retained its bioactivity and effectively blocked cells in the radiosensitive G2/M phase of mitosis. The taxol-radiation delivery system studied achieved an 83% decrease in tumor cell count compared to control. Taxol effectively sensitized Ewing's sarcoma cells to radiation with radiosensitivity shown to be independent of radiation dose at levels of dosages studied. This work has demonstrated that taxol can be effectively released from a biodegradable PMA-CPH microsphere delivery system while maintaining potent combined cytotoxic and radiosensitizing abilities.

Tissue engineering: orthopedic applications.

Because of an aging population and increased occurrence of sports-related injuries, musculoskeletal disorders have become one of the major health concerns in the United States. Current treatments, although fairly successful, do not provide the optimum therapy. These treatments typically rely on donor tissues obtained either from the patient or from another source. The former raises the issue of supply, whereas the latter poses the risk of rejection and disease transfer. This has prompted orthopedic surgeons and scientists to look for viable alternatives. In recent years, tissue engineering has gained increasing support as a method to treat orthopedic disorders. Because it uses principles of engineering, biology, and chemistry, tissue engineering may provide a more effective approach to the treatment of musculoskeletal disorders than traditional methods. This chapter presents a review of current methods and new tissue-engineering techniques for the treatment of disorders affecting bone, ligament, and cartilage.

Prevention of the spread of rabies to wildlife by oral vaccination of raccoons in Massachusetts.

OBJECTIVE: To evaluate the use of bait containing rabies vaccine to create a barrier of rabies-vaccinated raccoons in Massachusetts and to determine the effectiveness of various bait distribution strategies in halting the spread of rabies. DESIGN: Prospective study. SAMPLE POPULATION: Free-ranging raccoons. PROCEDURE: Baits were distributed twice yearly in a 207-km2 (80-mi2) area in the vicinity of the Cape Cod Canal. Bait density and distribution strategy varied among 3 treatment areas. Raccoons were caught in live traps after bait distribution and anesthetized; blood samples were obtained to measure serum antibody titers to rabies virus. Vaccination rates were determined by the percentage of captured raccoons with antibody titers to rabies virus > or = 1:5. In addition, raccoons with clinical signs of illness inside the vaccination zone and adjacent areas were euthanatized and submitted for rabies testing. RESULTS: The percentage of vaccinated raccoons differed significantly among the following 3 areas with various bait densities: high-density area with uniform bait distribution (103 baits/km2 [267 baits/mi2]) = 37%; low-density area with additional targeted bait distribution (93 baits/km2 [240 baits/mi2]) = 67%; and, high-density area with additional targeted bait distribution (135 baits/km2 [350 baits/mi2]) = 77%. Nineteen animals with rabies (15 raccoons, 3 skunks, 1 cat) were reported in the area just outside of the vaccination zone, but only 1 raccoon with rabies was reported from inside the vaccination zone. CLINICAL IMPLICATIONS: In this suburban study area, an approximate vaccination rate of 63% was sufficient to halt the spread of rabies in free-ranging raccoons. Compared with uniform bait distribution, targeting raccoon habitats increased vaccination rates.