Biologic scaffolds composed of extracellular matrix material (ECM) have been used for the repair of a variety of tissues including the lower urinary tract, esophagus, myocardium, and musculotendinous tissues, often leading to tissue-specific constructive remodeling with minimal or no scar tissue formation. Although use of ECM as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction is very promising, challenges remain in the process to manufacture bioactive gels from ECM that retain their bioactivity.
The methods of manufacturing bioactive gels from ECM described in prior art require the use of enzymes, and are time-consuming because they require aggressive purification steps, which may lead to depletion in the bioactivity of the gels and may present additional regulatory barriers to marketing. Thus, a need exists to manufacture bioactive gels from ECM that avoids cumbersome preparation and purification steps, yet results in gels that retain the bioactivity of the original material.
This invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels that retain bioactivity and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment, and neutralizing to provide bioactive gels.
The invention pertains to improved methods of manufacturing bioactive gels from ECM that retain sufficient bioactivity to positively assist in tissue repair. The method utilizes reagents that do not introduce additional regulatory burdens for market approval or clearance of the gel invention. The methods provide the ECM from one or more of the group consisting of, but not limited to, small intestine submucosa (SIS), urinary bladder submucosa (UBS), urinary bladder matrix (UBM) including epithelial basement membrane, porcine dermis (PD), and liver basement membrane (LBM). The method particularizes the ECM to a particle size in the range of about 1 μm to about 1000 μm, and solubilizes concentrations in the range of about 0.5 to 11% weight/volume (w/v) of particularized powder in sodium hydroxide (NaOH) in the range of 0.1 to 1.0 M.
The advantage provided by this method is that aggressive purification steps, which are costly and time-consuming, are avoided.