Design of a multiphase osteochondral scaffold. I. Control of chemical composition

This is the first in a series of articles that describe the design and development of a family of osteochondral scaffolds based on collagen-glycosaminoglycan (collagen-GAG) and calcium phosphate technologies, engineered for the regenerative repair of defects in articular cartilage. The osteochondral scaffolds consist of two layers: a mineralized type I collagen-GAG scaffold designed to regenerate the underlying subchondral bone and a nonmineralized type II collagen-GAG scaffold designed to regenerate cartilage. The subsequent articles in this series describe the fabrication and properties of a mineralized scaffold as well as a two-layer (one mineralized, the other not) osteochondral scaffold for regeneration of the underlying bone and cartilage, respectively. This article describes a technology through which the chemical composition-particularly the calcium phosphate mass fraction-of triple coprecipitated nanocomposites of collagen, glycosaminoglycan, and calcium phosphate can be accurately and reproducibly varied without the need for titrants or other additives. Here, we describe how the mineral:organic ratio can be altered over a range that includes that for articular cartilage (0 wt % mineral) and for bone (75 wt % mineral). This technology achieves the objective of mimicking the composition of two main tissue types found in articular joints, with particular emphasis on the osseous compartment of an osteochondral scaffold. Exclusion of titrants avoids the formation of potentially harmful contaminant phases during freeze-drying steps crucial for scaffold fabrication, ensuring that the potential for binding growth factors and drugs is maintained.