Chitosan [a (1----4) 2-amino-2-deoxy-beta-D-Glucan] is a unique polysaccharide derived from chitin. Several attempts have been made to use this biopolymer in biomedical field. The use of this material in the development of hemodialysis membranes, artificial skin, drug targetting and other applications are discussed. It appears, this novel biomolecule, biodegradable, and biocompatible, find applications in substituting or regenerating the blood/tissue interfaces. This polysaccharide having structural characteristics similar to glycosaminoglycans, seems to mimic their functional behaviour.

Chitosan-as a Biomaterial

Polyurethanes, having extensive structure/property diversity, are one of the most bio- and blood-compatible materials known today. These materials played a major role in the development of many medical devices ranging from catheters to total artificial heart. Properties such as durability, elasticity, elastomer-like character, fatigue resistance, compliance, and acceptance or tolerance in the body during the healing, became often associated with polyurethanes. Furthermore, propensity for bulk and surface modification via hydrophilic/hydrophobic balance or by attachments of biologically active species such as anticoagulants or biorecognizable groups are possible via chemical groups typical for polyurethane structure. These modifications are designed to mediate and enhance the acceptance and healing of the device or implant. Many innovative processing technologies are used to fabricate functional devices, feeling and often behaving like natural tissue. The hydrolytically unstable polyester polyurethanes were replaced by more resistant but oxidation-sensitive polyether polyols based polyurethanes and their clones containing silicone and other modifying polymeric intermediates. Chronic in vivo instability, however, observed on prolonged implantation, became a major roadblock for many applications. Presently, utilization of more oxidation resistant polycarbonate polyols as soft segments, in combination with antioxidants such as Vitamin E, offer materials which can endure in the body for several years. The applications cover cardiovascular devices, artificial organs, tissue replacement and augmentation, performance enhancing coatings and many others. In situ polymerized, cross-linked systems could extend this biodurability even further. The future will expand this field by revisiting chemically-controlled biodegradation, in combination with a mini-version of RIM technology and minimally invasive surgical procedures, to form, in vivo, a scaffold, by delivery of reacting materials to the specific site in the body and polymerizing the mass in situ. This scaffold will provide anchor for tissue regeneration via cell attachment, proliferation, control of inflammation, and healing.

Biomedical Applications of Polyurethanes: A Review of Past Promises, Present Realities, and a Vibrant Future:

Methods for the treatment of collagenous tissues for bioprostheses

Experimental assessment of small intestinal submucosa as a bladder wall substitute.

Role of mechanical stress in calcification of aortic bioprosthetic valves

Calcification in blood pumps.

A trileaflet valve, compression molded of Hexsyn rubber, was evaluated as a component in temporary blood pumps. A pair of valves was integrated into an LVAD which was tested in vitro and in vivo. The valve's hemodynamic performance was satisfactory and the blood compatibility was excellent in a three-week, in vivo experiment conducted to demonstrate performance in a short-term application. Hexsyn, which has excellent properties and produces high quality, complex components with ease of fabrication, offers a potential for low-cost blood pump valves.

Hexsyn trileaflet valve: application to temporary blood pumps.

A TAH system utilizing two pusher-plate type pumps was developed and tested in two calves for 45 and 108 days with excellent results. A Hall effect sensor was utilized to operate each pump with a full stroke at variable rates (VR); each pump was then allowed to run independently at different rates depending on its own preload and afterload. With this system, the animals' atrial pressures were kept to near-normal levels (less than 10 mmHg). However, significant differences in the left and right pump flows were observed (left higher than right) and they ranged from 5 to 30% of the left flow with a mean of 15%. These flow differences may be due to the bronchial circulation and related shunts. Right pump flows averaged 70 to 95 ml/min-kg and circulating blood volume ranged from 67 to 95 ml/kg. When various control modes including fixed rate and master-slave type simultaneously or alternatively ejecting VR modes were applied in the same animals and both pump flows were forced to be equal, unphysiological atrial pressures resulted. This result indicates that perhaps left and right flow differences are necessary physiological conditions to regulate the atrial pressures within normal ranges. Metabolic data also indicated that under simultaneously and alternately ejecting modes, A-V O2 content differences were increased due to decreased right pump flow as compared with those of the free-running VR mode. The left and right free-running VR mode of operation imposed minimal constraints on the animals' cardiovascular system and therefore yielded excellent hemodynamic and metabolic results.

Pusher-plate type TAH system operated in the left and right free-running variable rate mode.

The objective of this study is to define the human thorax in a quantitative statistical manner such that the information will be useful to the designers of cardiac prostheses, both total replacement and assist devices This paper pertains specifically to anatomical parameters relevant to the total artificial heart Methods were developed for generating an integrated, statistical model of the anatomical structures within the human thorax These methods involve definition of the anatomy in four areas: chest wall, pericardium, vascular connection locations, and great vessels Results are presented in three dimensional scale views of the human thorax showing the main features pertinent to cardiac prosthesis implantation Statistical variability of this data is also included Measurements were obtained from a number of sources and represent both normal and diseased patients The ERDA total artificial heart was shown to successfully fit the fiftieth percentile adult male human

Human thoracic anatomy relevant to implantable artificial hearts.

Human thoracic anatomy was studied using computed tomography (CT) for the development of a totally implantable electrohydraulic left ventricular system [Nimbus, Inc., and The Cleveland Clinic Foundation (CCF)]. To obtain statistical dimensional information for the chest wall, apex of the heart, and aorta, routine calibrated CT scans of 18 men and 17 women were analyzed. A special radiopaque vest was worn by the patient just prior to the scanning and X-ray procedures, so that each transverse scan could be assigned to a specific chest level after combination with a standard vertical referencing system set on the patient's radiogram. A polar coordinate system and direct measurement of transverse distances from the vertical column to points on the chest wall were employed to define collectively the shape and size of the intrathoracic surface of the chest wall. Locations of the aorta and apex were described by measuring their normalized distances from the midline and vertical column to the intrathoracic surface of the lateral and anterior chest wall. The radius of curvature of the intrathoracic wall lateral to the left ventricle was determined to be approximately 10.4 cm for the average adult male chest. The present CCF intrathoracic pump with this curvature fits fairly well in both the average and individual thoraxes of these adult males. The location of the aorta, particularly of the descending aorta, was used to determine the optimal outlet design. The most critical anatomical area was the apex location. For adult males, an average distance of 2.8 cm from the apex to the internal chest wall was found. Because of this small dimension, careful design of the inflow port is being performed to avoid anatomical mismatch.

Raymond J. Kiraly

Papers

Calcification in blood pumps.

Hexsyn trileaflet valve: application to temporary blood pumps.

Pusher-plate type TAH system operated in the left and right free-running variable rate mode.

Human thoracic anatomy relevant to implantable artificial hearts.

Human Thoracic Anatomy Based on Computed Tomography for Development of a Totally Implantable Left Ventricular Assist System