**Author details**

osteogenic markers (which might be regarded as an unwanted differentiation), the results remained inconclusive [123]. Further reports on gene therapy dealing with the tendon-to-

Growth factors or drugs aiming at the support of the healing process can be injected directly to the wound site. However, one major problem encountered by doing that is that activity of such biological molecules (often proteins) is short-lived. Hence, a suitable strategy is to take a delivery device realized by an implant material or a TEC allowing sustained release of the drug to the repair site over longer periods of time. Among many others, one interesting growth factor supporting tendon rupture repair is PDGF-BB [125]. It is not only mitogenic but also angiogenic and chemotactic—ending up in accelerated cell proliferation, migration, increased collagen synthesis and vascularity, and finally improved biomechanics of the repaired tendon [125]. Hence, a random-fiber electrospun delivery device in form of a tube was developed which not only allowed the controlled release of PDGF-BB [11], but also acted as an effective physical anti-adhesion barrier [126]. Without the growth factor included, this TEC neither evokes any adverse cellular effects nor influences inflammation reaction toward the implant [90, 91]. With the growth factor, biomechanics improved significantly, underlying promising

Another approach using tendon-derived progenitor/stem cells seeded onto an aligned randomfiber mesh made of PLLA discovered that tenogenesis of these stem cells was not triggered by the aligned fibers, which was previously hypothesized. Because the expression of histone deacetylases was found to be reduced in the progenitor cells seeded on the aligned fibers, a small molecule (Trichostatin A), which is an inhibitor of histone deacetylases, was incorporated in the aligned fiber mesh. As a result of this bioactive mesh, the corresponding progenitor cells seeded on this TEC showed better tenogenesis and when implanted in a rat Achilles tendon model, the healing was accelerated and improved compared to non-Trichostatin TECs [83].

Tissue engineering of tendon substitutes and grafts is a viable option to close critical size defects. The choice of a suitable scaffold material, natural or synthetic, is a decision which should be based on biomechanical baseline values of native tendon tissues and which will direct/affect biocompatibility, cell attachment, or incorporation of factors that support the healing process. Cell seeding and cultivation may be performed under static conditions as well as in dynamic systems using bioreactors. Bioreactors offer perfusion flow resulting in shear stress; additional mechanical stimulation by stretching the cell-seeded TEC may help to improve the mechanical characteristics of the TEC and trigger the desired differentiation if stem cells are involved. Growth factors incorporated in TECs may also support the healing

gone interface also used BMPs [124].

170 Tissue Regeneration

**6. Drugs to stimulate the healing**

perspectives for this bioactive implant.

process of the lacerated tendon tissue.

**7. Conclusion**

Johanna Buschmann

Address all correspondence to: johanna.buschmann@usz.ch

Plastic Surgery and Hand Surgery, Department of Surgical Research, University Hospital Zurich, Switzerland
