Extracts for the regeneration of ligaments

Inventors

Gottardi, Riccardo Luca • Rothrauff, Benjamin Burke • Tuan, Rocky Sung Chi • Kihara, Shinsuke

Assignees

RiMed Foundation • University of Pittsburgh

Abstract

Provided herein is a ligament ECM soluble fraction useful for the growth and regrowth of ligament tissue. Methods of preparation of the soluble fractions and use of the soluble fractions in growth or regrowth of ligament tissue also are provided.

Core Innovation

The invention relates to a composition comprising a urea-soluble fraction of decellularized, nuclease-digested anterior cruciate ligament or posterior cruciate ligament tissue. The tissue is comminuted, decellularized in a detergent or emulsifier, and digested with a nuclease, then soluble components are dissociated from insoluble components by exposure to urea and fractionated to separate the urea-soluble fraction from insoluble fibrillar collagen.

After separating the urea-soluble fraction, the urea is removed and the resulting composition comprises the urea-soluble fraction together with a pharmaceutically-acceptable excipient. The soluble fraction is described as cell-free and DNA/RNA-free, and is used for ligament repair and ligament growth/regeneration.

The disclosed use extends to preparing a ligament structure by applying an effective amount of the urea-soluble fraction to a growth matrix. The document also describes orthopedic ligament repair, including cruciate ligaments such as ACL and PCL, dentistry use for periodontal ligament for tooth avulsion, and delivery with ligament structures/scaffolds, controlled-release structures, fibrin glue, and an optional lyophilization in a kit format.

Claims Coverage

The provided claim set includes three independent claims: a composition, a method of preparing a composition to stimulate ligament growth, and a method of preparing a ligament structure. Across these claims, the inventive content centers on a urea-soluble fraction obtained from decellularized, nuclease-digested ACL/PCL tissue by urea dissociation and fractionation from insoluble fibrillar collagen, followed by urea removal.

Across the independent claims, the core claim coverage centers on producing a urea-soluble fraction from decellularized, nuclease-digested ACL/PCL tissue by urea-based dissociation and fractionation away from insoluble fibrillar collagen, with urea removal, then using that fraction either as part of a composition with a pharmaceutically-acceptable excipient or by applying an effective amount to a growth matrix to prepare a ligament structure.

Stated Advantages

Documented Applications