Collagen gel systems for sustained delivery and tissue engineering.

Collagen gels are flowable, suggesting the possibility of an easily injectable, biocompatible drug delivery matrix. Sustained release of therapeutic molecules from collagen matrices, however, is beset with difficulties. Fibrillar collagen gels have an effective pore size of several tens of nanometers, too large to control release by hindered diffusion. To control release, it is necessary to rely on binding of the active agent to collagen, either by covalent or non-covalent bonds, or on sequestering in a secondary matrix. Such steps rapidly increase the complexity of the system. Non-fibrillar collagen has a lower effective pore size (4-6 nm), but it dissolves rapidly in vivo (approximately 24 h). For tissue engineering applications, collagen gels are more attractive, since they can act as a "cage" to retain cells or as gene delivery complexes, which are larger than drugs and therapeutic proteins. The gels have limitations in terms of strength, but reinforcement with solid components and alignment during gelation and culture can improve performance.