Tissue engineering and regenerative medicine: recent innovations and the transition to translation

Abstract

The field of tissue engineering and regenerative medicine (TERM) has exploded in the last decade. In this Year (or so) in Review, we highlight some of the high impact advances within the field over the past several years. Using the past as our guide and starting with an objective premise, we attempt so to identify recent "hot topics" and transformative publications within the field. Through this process, several key themes emerged: (1) tissue engineering: grafts and materials, (2) regenerative medicine: scaffolds and factors that control endogenous tissue formation, (3) clinical trials, and (4) novel cell sources: induced pluripotent stem cells. Within these focus areas, we summarize the highly impactful articles that emerged from our objective analysis and review additional recent publications to augment and expand upon these key themes. Finally, we discuss where the TERM field may be headed and how to monitor such a broad-based and ever-expanding community.

FIG. 1.

The rise of tissue engineering and regenerative medicine (TERM). (Results obtained via Scopus^® search using key words “tissue engineering” OR “regenerative medicine”). Color images available online at www.liebertpub.com/teb

FIG. 2.

Number of citations each year postpublication (as a percentage of total TERM articles in that year) for the top 20 TERM publications. Data presented as box and whiskers plot featuring median, interquartile range, and minimum/maximum (Langer and Vacanti excluded as an outlier).

FIG. 3.

Top 50 TE and RM publications for 2010–2012 with the outliers circled. These publications formed the basis of this review and defined discussion categories.

FIG. 4.

Use of decellularized tissue matrix for TE applications. Whole lungs can be readily decellularized through perfusion techniques [right upper lobe (RUL), right middle lobe (RML)] (A). When implanted in vivo, such tissues are perfused by red blood cells and maintain partial function in the short-term (B). Recellularized liver matrix also maintains similar structure and cellular viability and phenotype (C). Scale bar=100 μm. Decellularized tissue-engineered vascular grafts maintain patency when implanted and allow repopulation with native cells [graft (g), carotid artery (ca), adventitia (a)] (D). White arrowhead points out alpha-smooth muscle actin-positive cell. Scale bars=100 μm. (Adapted from Petersen et al., Ott et al., Uygun et al., and Dahl et al., [with permission from AAAS and MacMillan Publishers, Ltd]).

FIG. 5.

Bioscaffolds for bone regeneration. Nanofibers with macroscopic perforations and alginate releasing bone morphogenetic protein-2 (BMP-2) were placed within a critically sized bone defect (A). Micro-computed tomography images showing increased bone formation with scaffold treatment (B). (Adapted from Kolambkar et al. [with permission from Elsevier]).

FIG. 6.

Recent clinical applications of TERM approaches. A tissue-engineered urethra can maintain function in patients in the long-term (A). Injection of cardiosphere-derived stem cells can reduce scar size in patients postinfarction (B). (Adapted from Raya-Rivera et al. and Makkar et al. [with permission from Elsevier]). CDC, cardiosphere-derived cells.

FIG. 7.

Induced pluripotent stem cells (iPSCs) can produce cartilage-like matrix. Collagen immunohistochemistry for matrix made by passage 2 iPSCs sorted via expression of type II collagen (GFP+). (Adapted from Diekman et al. [with permission from the National Academy of Sciences]).