Translation from Research to Applications

Abstract

The article summarizes the collective views expressed at the fourth session of the workshop Tissue Engineering-the Next Generation, which was devoted to the translation of results of tissue engineering research into applications. Ernst Hunziker described the paradigm of a dual translational approach, and argued that tissue engineering should be guided by the dimensions and physiological setting of the bodily compartment to be repaired. Myron Spector discussed collagen-glycosaminoglycan (GAG) scaffolds for musculoskeletal tissue engineering. Jeanette Libera focused on the biological and clinical aspects of cartilage tissue engineering, and described a completely autologous procedure for engineering cartilage using the patient's own chondrocytes and blood serum. Arthur Gertzman reviewed the applications of allograft tissues in orthopedic surgery, and outlined the potential of allograft tissues as models for biological and medical studies. Savio Woo discussed a list of functional tissue engineering approaches designed to restore the biochemical and biomechanical properties of injured ligaments and tendons to be closer to that of the normal tissues. Specific examples of using biological scaffolds that have chemoattractants as well as growth factors with unique contact guidance properties to improve their healing process were shown. Anthony Ratcliffe discussed the translation of the results of research into products that are profitable and meet regulatory requirements. Michael Lysaght challenged the proposition that commercial and clinical failures of early tissue engineering products demonstrate a need for more focus on basic research. Arthur Coury described the evolution of tissue engineering products based on the example of Genzyme, and how various definitions of success and failure can affect perceptions and policies relative to the status and advancement of the field of tissue engineering.

Scaffold Design and Manufacturing: From Concept to Clinic

“…A 510-K pathway for a tissue engineering scaffold may cost $ 5-10 million, while a PMA pathway may cost well over $ 50 million. [76] In summary, issues beyond initial scaffold design, material synthesis, and manufacturing research are often more than 50% of the work that goes into making a scaffold a clinical product. Many technologies reach the spin-off stage but then face either significant regulatory issues, significant manufacturing scaling issues, or lack of surgical acceptance.…”

Three-Dimensional-Construct Bioreactor Conditioning in Human Tendon Tissue Engineering

“…8,32 Our experiments showed superior properties in dynamicloaded constructs, compared with static-loaded ones. Similarly, using an in vivo model, Liu et al illustrated gains in tensile strength following dynamic-loading.…”

“…8 For the optimization of construct biomechanics in this study, the latter group of devices was utilized.…”

“…11,12,22,23 Successful tissue engineering involves the orchestrated interaction of a triad of cells, growth factors, and a 3D matrix in an ex vivo setting. 8,24 In nature, however, functional regeneration involves a fourth factor-physical force, such as pressure, flow, and shear. 22 While early tissue engineering efforts involved letting in vivo physical forces come into play naturally after reimplantation of engineered tissue, it later became apparent that mechanical stimulation should be an integral part of any attempt to engineer functional tissue where mechanical function is physiologically important.…”

“…The use of bioreactors to improve the remodeling process of ligaments and tendons is not new. 8 Cyclic stretching of cells in vitro has been shown to increase collagen synthesis, 26 induce tendon fibroblast differentiation, 27,28 realign cells along the direction of maximal strain, 29 and upregulate gene expression of collagen types I and III, and tenascin C. 30 On a macro scale, application of mechanical force to 3D constructs converts TECs into phenotypically appropriate tissue. 11 Our small-sample size pilot study findings from the LCB experiments suggest that both reseeding and cyclic-loading are important factors for engineering of TECs based on natural scaffolds.…”