A novel class of bioresorbable, composite fiber structures loaded with bioactive agents has been developed and studied by us. These unique polymeric structures are designed to combine good mechanical properties with a desired controlled release profile, in order to serve as basic elements of broad range of medical implants and scaffolds for tissue regeneration applications. All types of bioactive agents, water soluble and water insoluble agents, can be incorporated within these structures, while preserving their activity. This study is expected to lead to the engineering of new implants and scaffolds, and to advance the field of bioresorbable medical implants  and tissue regeneration.

The skin is the largest tissue of the body and has many different functions. Wounds with tissue loss include burn wounds, wounds caused as a result of trauma, abrasions or as secondary events in chronic diseases such as venous stasis, diabetic ulcers and pressure sores. However, wounds with significant bacterial contamination are problematic, and wound dressings that release antibacterial agents would therefore be advantageous. The major drawback associated with the current dressing solutions is the need to remove the dressing consequently causing pain and possibly harming the vulnerable underlying skin.
We developed lately biodegradable fibers loaded with antibacterial agents, such as ceftazidime, gentamicin and mafenide acetate. These fibers can be used as basic elements of biodegradable burn and ulcer dressings which release antibiotics in a controlled manner. Growth factors can be incorporated in these fibers, in addition to the antibiotics, for enhanced tissue regeneration. Our unique process of composite fiber formation enables to preserve the activity of these sensitive biomolecules. Also, the porous shell's structure enables water absorption by the wound dressing. Such novel wound dressings, which will probably enable better and faster healing, will advance the field of wound care. (In collaboration with Prof. Israela Berdicevsky and Prof. Yehuda Ullmann, Technion's Faculty of Medicine, Haifa, Israel).

Percutaneous transluminal coronary angioplasty (PTCA) has been established as an alternative to coronary artery bypass to treat selected patients with coronary arterial disease. In many cases metal stents are used in order to keep the blood vessel wall patent for long period of time. Restenosis commonly occurs within 3-6 months after coronary intervention, and it rarely occurs thereafter.  Considering the short-term need and the potential for long-term complications with metallic stents, biodegradable polymeric stents may be an appropriate alternative. A biodegradable stent may also be useful for the local administration of pharmacological agents directly to the site of PTCA.
Our composite fiber structures can be used as the basic elements of biodegradable endovascular stents that mechanically support blood vessels, while delivering drugs such as paclitaxel directly to the blood vessel wall. Paclitaxel is a potent cell proliferation inhibitor and is known to be very effective in the treatment of cancer as well as in preventing restenosis. (In collaboration with Prof. Yoel Kloog, Faculty of Life Sciences, Tel-Aviv University, Israel).

Antibiotic-Eluting Bioresorbable Film Structures 
for Preventing Bacterial Infections

Adhesion of bacteria to biomaterials and the ability of many microorganisms to form biofilms on foreign bodies are well-established as major contributors to the pathogenesis of implant-associated infections. Treatment of bone infection remains problematic, due to the difficulty of systemically administered antibiotics to locally penetrate bone. The current research addresses this issue by focusing on the development and study of novel gentamicin-loaded bioresorbable films designed to serve as “coatings” for fracture fixation devices which will prevent implant-associated infections.
In collaboration with Prof. Israela Berdicevsky from the Technion's Faculty of Medicine, various bioresorbable films containing antibacterial agents, such as gentamicin, have been developed through solution processing. The effects of polymer type, drug content and processing conditions on the drug release profile are studied with respect to film morphology. Various gentamicin concentrations that were released from the films with time, exhibited efficacy against bacterial species known to be involved in orthopedic infections. The developed systems can be applied on the surface of any metallic or polymeric fracture fixation device, and may therefore comprise a significant contribution to the field of orthopedic implants.

Periodontal diseases refer to inflammatory conditions in the gums which progress to loss of alveolar bone and loss of teeth. In collaboration with Prof. Itzhak Binderman form Tel-Aviv's Faculty of Dental Medicine, we developed lately bioresorbable poly(DL-lactic - co - glycolic acid) (PDLGA) films loaded with the antibiotic agent metronidazole. The films were prepared by solution processing, where film structuring is obtained, according to a specific method of preparation. These films are designed to be inserted into the periodontal pockets and treat infections upon metronidazole controlled release phase, for at least one month. The effects of copolymer composition and drug content on the release profile, on cell growth and on the bacterial inhibition have been investigated.

Organ or tissue deficiency or loss is one of the most frequent and devastating problems in human healthcare. Integration of biomaterials, engineering and biology are applied to the development and study of functional substitutes for damaged tissues. Tissue regeneration involves the preparation of polymeric structures that serve as degradable scaffolding for bioactive molecules or cells as well as the study of their structure and properties. The main obstacle to successful drug or protein incorporation and delivery from degradable scaffolds is the inactivation of bioactive molecules by exposure to high temperatures or harsh chemical environments.
In the present study we develop and study novel bioresorbable film structures loaded with bioactive agents. Their high porosity is designed to enable tissue growth into the scaffold. The scaffolds are prepared using the freeze drying of inverted emulsions technique, which enables to incorporate very sensitive bioactive molecules, such as growth factors and differentiating factors, without affecting their activity. Our study focuses on the effect of the emulsion's formulation on the porous shell structure and on the resulting cumulative release of bioactive agents from the scaffolds for 28 days. We also investigate the effect of these scaffolds on cell adhesion and growth of human fibroblasts in culture.
 

There is an increasing need to develop new biodegradable materials to be used in skin tissue engineering, wound cover or as dressings and barrier membranes, since there is a high demand for skin replacement and skin repair treatments. One approach involves the use of biodegradable polymers from renewable resources, such as starch, collagen, gelatin, chitosan, soy protein and casein. These polymers are widely available in nature and are biodegradable and non-toxic. Soybean is a natural material made of protein and carbohydrate fractions, an oil fraction and minerals. Soy protein, the major component of soybean has the advantages of being economically competitive and present a good water resistance as well as storage stability. Soy protein-based structures can potentially be used for the delivery of bioactive agents that aid wound healing, such as antibiotics. In this project we develop and study soy protein-based scaffolds with controlled delivery of bioactive agents. These scaffolds are designed to be use in wound healing applications.

As described above, bioresorbable films and fibers loaded with drugs and proteins are used in our studies as basic elements for various medical devices. The ability to predict the release profile of bioactive agents from these units can serve as a preliminary stage in each study and may save weeks of in vitro drug release experiments. Furthermore, some of the bioactive agents (especially growth factors used in tissue regeneration applications) are very expensive and modeling of such systems can therefore be useful.
This study aims to develop mathematical models based on physical phenomena, in order to predict drug release profiles from bioresorbable films and fibers. In addition, these models are used to elucidate the effects of the polymer’s degradation rate and degree of crystallinity on the resulting controlled release profile, and they can also be used for exploring and measuring physical properties that are difficult to measure using conventional in vitro methods.