The invention provides biomatrix compositions comprising cross-linked lactoferrin, either alone or in combination with other organic or inorganic components. Also provided are methods of making and using the biomatrix compositions. As described herein, cross-linked lactoferrin biomatrix retains the bioactivities of the lactoferrin molecule. The biomatrix composition can act as a matrix for cell adhesion and growth and is particularly useful in musculoskeletal tissue regeneration. The biomatrix compositions can be pre-formed or injectable and can act as a cell, drug or protein delivery vehicle.