Chasing the Paradigm: Clinical Translation of 25 Years of Tissue Engineering

Abstract

In the past 25 years, the tissue engineering field has made incredible strides in developing tangible therapies for patients in need. Applications of the tissue engineering paradigm, involving varying configurations of cells, materials, and biochemical factors, have been explored for their regenerative capacity of virtually all tissue types. The impact and learning opportunities of current tissue engineering that inspired clinical successes are summarized. In addition, challenges associated with the translation and scale-up of therapies and replacements for complex organs, such as the heart and liver, are addressed. Platforms of research thrusts, specifically cell source, materials, fabrication, scalability, and Food and Drug Administration regulatory changes, and their respective innovations are identified for their potential to address these problems. Ideally, through their progress, tissue engineering strategies can be used to create a diverse range of easily accessible patient-specific treatments that more effectively improve quality of life.

Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: Inspiring a new Kind of Medicine

“…Regenerative medicine using 3-D printing of extracellular matrix with stem cells is an increasing viable option to repair and replace diseased and damaged tissues such as cartilage. Collagen matrix combined with chondrocytes, marketed as matrix-associated autologous chondrocyte implantation (MACI), was approved by the FDA for knee cartilage defects [2,6,206]. The use of decellularized ECM for cartilage treatment is hindered by the need for compact cartilage tissue.…”

“…Used mostly to induce and promote cell growth and differentiation, growth factors can have severe side effects and case toxicity [223,224]. Several alternatives have been suggested including the use of medicinal remedies and the optimization of the amounts of growth factors to be used [2,225]. Efforts to get regenerative medicine technologies to patients fast are hampered by regulatory requirements as stipulated by the FDA.…”

“…Several discussions have taken place on the topic of stem cell and ECM use in regenerative medicine applications, with hope that in future therapies and products shown to be safe can be approved without delay [6,226]. One area that might require expedited approval is the use of autologous stem cells and ECMs [2].…”

Recent Advances in Enabling Technologies in 3D Printing for Precision Medicine

“…These considerations are especially relevant for bioactive components, which may include elements such as cells, DNA, extracellular matrix proteins, or growth factors. Many exciting advances in the use of bioactive components for precision medicine have already been implemented in clinical settings for non‐3D printing applications, such as personalized gene therapies or matrix‐induced autologous chondrocyte implantation . Further, advances in gene therapy, cell culture, and cell manufacturing offer an array of exciting new components to incorporate into bioinks for precision medicine .…”

In situ Enabling Approaches for Tissue Regeneration: Current Challenges and New Developments

“…The need for alternative approaches has led to the foundation of tissue engineering (TE), an exciting field of research that over the last 25 years has used materials in the presence or absence of cells and biochemical factors to restore, maintain, or improve biological tissues (Langer and Vacanti, 1993). During this period, scientists have recognized that tissue reconstruction is an extremely complex task that cannot be performed by simply bringing cells and materials together (Hoffman et al, 2019). The exciting path of TE, however, allowed the scientific community to gain a deeper understanding of cell and stem cell biology, uncovering the importance of the properties of the extracellular matrix (ECM) in directing cell behavior.…”