Nathaniel Bachrach
Research and Development, LifeCell Corporation, Poland
One can define regenerative medicine as medical practice that harnesses the body’s intrinsic capacity for self-renewal and its ability to regenerate tissues and organs. Historically, within the context of tissue engineering or regenerative medicine, the basic paradigm to develop a product that will translate to the clinic has been to require: 1. A structure that provides an immediate physical function and a 3-D scaffold for cells, 2. Cells that induce the de novo tissue formation and 3. Growth factors and cytokines that modulate the biological response. A review of clinical applications of regenerative medicine products indicates that native extracellular matrix (ECM)-based scaffolds have been introduced to patient care most successfully. Examples include demineralized bone matrices used in orthopedic surgery and soft tissue-based matrices used for soft tissue reconstruction. One reason for this commercial and clinical success is that these tissue matrices have been introduced to the market place as medical devices, while the regulatory hurdles for cell and active molecule based products are more challenging. The clinical success of these products challenges the old paradigm and suggests that the critical element for successful tissue regeneration is the ECM. The host has cells capable of regenerating tissues and much of the signaling required for tissue specific regeneration can come directly and indirectly from the matrix. As cells from the host interact with the matrix they can add additional signaling through growth factors and cytokines to modulate biologic response. In this way, all three elements are achieved through a simpler delivery paradigm.
A New Paradigm
Matrices engineered to provide the ideal regenerative environment may include biochemical cues, binding sites, micro and macro structure and mechanics, and physico-chemical properties and will successfully leverage the body’s capacity to regenerate. Key factors that are critical when introducing an ECM-based matrix in clinical practice are scientific, clinical, and economic data. Scientific data encompass product characterization (e.g. chemistry), and preclinical work that focuses on the immune response of the product using appropriate animal models.
The future will likely see the introduction of newer ECM-based technologies designed to target challenging clinical needs previously thought to require cells and active factors. This new paradigm for tissue engineering to provide regenerative solutions will be even more essential to exploit as changes in the regulatory environments and health care systems world-wide make advancements in alternative strategies even more challenging.