Zonal release of proteins within tissue engineering scaffolds

Abstract

The manufacture of a scaffold for tissue engineering applications that can control the location and timing of growth factor release is described. The scaffold is formed by the sintering of poly(DL-lactic acid) (P(DL)LA) microparticles, plasticized with poly(ethylene glycol) (PEG), although the method can be used for many other polymer types. The microparticles were loaded with model proteins, trypsin and horseradish peroxidase (HRP), or recombinant human bone morphogenetic protein-2 (rhBMP-2). Entrapment efficiencies above 75% were achieved using a solid-in-oil-in-water system. Controlled release of active protein was achieved for at least 30 days. Microparticles were built into protein-loaded or protein-free layers and release of the protein was restricted to zones within the scaffold. Cell response to rhBMP-2 was tuneable by changing the dose of the rhBMP-2 released by varying the ratio of protein-loaded and protein-free microparticles within scaffolds. Zonal activity of rhBMP-2 on C2C12 cells was demonstrated. The scaffolds may find utility in applications where gradients of growth factors within 3D templates are required or where zonation of tissue growth is required.

Tissue Engineering of Articular Cartilage with Biomimetic Zones

“…105 Scaffolds with protein gradients have also been generated using sintered microparticles containing enzymes or growth factors. 106,107 Nonetheless, the utility of gradient scaffolds in engineering articular cartilage with biomimetic zones remains to be determined.…”

Tissue engineering: strategies, stem cells and scaffolds

“…These versatile subunits can be produced using droplet formation of solvents (Suciati et al 2006) or by spraying (Hao et al 2004;Whitaker et al 2005). Setting of a microparticle slurry was initially performed using the attraction between biotin in one set of beads and avidin in another.…”

“…angiogenesis, at particular sites throughout scaffolds. This system has been demonstrated by Suciati et al 2006, in which PLA/PEG microparticles were loaded with proteins such as horseradish peroxidase, trypsin or BMP-2. These particles were then sintered to form distinct layers.…”

Joint Cartilage Tissue Engineering and Pre-Clinical Safety and Efficacy Testing

“…A requirement for the successful delivery system is that the active molecules are protected against degradation until time of release. The systems range from very basic soaking of the scaffold in growth factor suspension (Kanematsu et al, 2004) to highly sophisticated release systems, where attempts are being made to closely mimic the stage specific differentiation process or even create dual tissues by releasing different molecules at controlled time points, dosages, and locations in the scaffold Suciati et al, 2006). These highly complex systems are still in their infancy.…”