IMPAIRED TENDON FUNCTION RESULTING FROM THE FORMATION OF TENDON ADHESION REPRESENTS A MAJOR COMPLICATION WHICH CAN OCCUR FOLLOWING SURGICAL REPAIR OF A DAMAGED OR LACERATED TENDON.

IMPAIRED TENDON FUNCTION RESULTING FROM THE FORMATION OF TENDON ADHESION REPRESENTS A MAJOR COMPLICATION WHICH CAN OCCUR FOLLOWING SURGICAL REPAIR OF A DAMAGED OR LACERATED TENDON. ONE GOAL OF SUCCESSFUL SURGERY, THEN, IS TO PREVENTOR MINIMIZE SCAR TISSUE FORMATION AT THE WOUND SITE. PRELIMINARY STUDIES SUGGEST THAT HYALURONIC ACID (HA) APPLIED BETWEEN THE TENDON AND ITS SHEATH MIGHT DETER ADHESION FORMATION WHILE SIMULTANEOUSLY PROMOTING HEALING OFTHE TENDON. USING A PHARMACEUTICAL PREPARATION OF HYALURONIC ACID TO BE PRODUCED AND CHARACTERIZED AT OUR FACILITY, WE WILL DETERMINE EFFECTIVENESS BASED ON TENDON ADHESION FORMATION IN THE RABBIT TENDON ADHERENCE MODEL SYSTEM. GENERAL CRITERIA WILL ENCOMPASS MICROANGIOGRAPHY, HISTOLOGY, AND BIOMECHANICAL TESTING. EXPERIMENTALLY WE WOULD VARY THE CHAINLENGTH OF THE PREPARATION IN ORDER TO EVALUATE THE EFFECTIVENESS OF EQUAL HYALURONIC ACID CONCENTRATIONS OF SHORT (LESS THAN 100K), INTERMEDIATE (100-750K), AND LONG CHAIN (GREATER THAN 750K) MOLECULAR WEIGHTS.WE ANTICIPATE THAT THE STUDIES PROPOSED HEREIN (SEE SPECIFICAIMS) CAN DEFINITELY DETERMINE THE EFFICACY OF AN HA PREPARATION USED AT THE TIME OF SURGERY TO PREVENT ADHESION FORMATION. IN PARTICULAR, DETERMINATION OF AN EFFECTIVE CHAIN LENGTH IN THE ABOVE PROCESS WOULD ALLOW LESS VISCOUS PREPARATIONS TO BE PRODUCED THUS FACILITATING APPLICATION DURING SURGICAL PROCEDURES. HYALURONIC ACID IS THE PRIMARY SUBSTITUENT OF INTRA-ARTICULAR FLUID, PROVIDING A HIGH VISCOSITY, NUTRIENT MEDIUM WITHIN THE JOINT. INTRA- ARTICULAR SYNOVIAL FLUID WHICH IS APPROXIMATELY 90% BY WEIGHT HA (EXCLUDING WATER), IS THE PHYSIOLOGICAL SUBSTANCE BATHING THE TENDON. THUS, THE IMPLICATION OF THE APPROACH TAKEN IN THIS PROPOSAL IS THAT REPLACEMENT OF THE PRINCIPLE COMPONENT OF SYNOVIAL FLUID (HYALURONIC ACID) AT THE TIME OFSURGERY WILL ELIMINATE TENDON ADHESIONS AND DRAMATICALLY IMPROVE THE PROGNOSIS AFTER TENDON SURGERY. WE ARE CURRENTLY INVOLVED WITH E.R. SQUIBB & SONS, IN OBTAINING FDAAPPROVAL FOR THE INTRA-ARTICULAR USE OF HA IN HORSES FOR TREATMENT OF INFLAMMATORY AND OTHER DEGENERATIVE JOINT CONDITIONS. THEY HAVE SHOWN INTEREST IN POTENTIAL HUMAN APPLICATIONS OF HA SUCH AS THAT DETAILED IN THIS PROPOSAL. SINCE HA IS UBIQUITOUS TO MANY TISSUES AND FLUIDS OF PHYSIOLOGICAL ORIGIN SUCH AS CONNECTIVE TISSUE, INTRA- ARTICULAR FLUIDS, AND VITREOUS, THIS PROPOSAL IS RELEVANT TO THE MISSION OF THE NATIONAL INSTITUTE OF ARTHRITIS, DIABETES, AND DIGESTIVE AND KIDNEY DISEASE.