The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion.

Background: The Ponseti method is the preferred technique to manage idiopathic clubfoot deformity; however, there is no consensus on the expected relapse rate or the percentage of patients who will ultimately require a corrective surgical procedure. The objective of the present systematic review was to determine how reported rates of relapsed deformity and rates of a secondary surgical procedure are influenced by each study's length of follow-up.Methods: A comprehensive literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed to identify relevant articles. The definition of relapse, the percentage of patients who relapsed, the percentage of feet that required a surgical procedure, and the mean duration of follow-up of each study were extracted. Pearson correlations were performed to determine associations among the following variables: mean follow-up duration, percentage of patients who relapsed, percentage of feet that required a joint-sparing surgical procedure, and percentage of feet that required a joint-invasive surgical procedure. Logarithmic curve fit regressions were used to model the relapse rate, the rate of joint-sparing surgical procedures, and the rate of joint-invasive surgical procedures as a function of follow-up time.Results: Forty-six studies met the inclusion criteria. Four distinct definitions of relapse were identified. The reported relapse rates varied from 3.7% to 67.3% of patients. The mean duration of follow-up was strongly correlated with the relapse rate (Pearson correlation coefficient 5 0.44; p , 0.01) and the percentage of feet that required a joint-sparing surgical procedure (Pearson correlation coefficient 5 0.59; p , 0.01). Studies with longer follow-up showed significantly larger percentages of relapse and joint-sparing surgical procedures than studies with shorter follow-up (p , 0.05). Conclusions:Relapses have been reported to occur at as late as 10 years of age; however, very few studies follow patients for at least 8 years. Notwithstanding that, the results indicated that the rate of relapse and percentage of feet requiring a joint-sparing surgical procedure increased as the duration of follow-up increased. Longer-term followup studies are required to accurately predict the ultimate risk of relapsed deformity. Patients and their parents should be aware of the possibility of relapse during middle and late childhood, and, thus, Disclosure: There was no source of external funding for this study. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/ JBJSREV/A462).

The development of a relapse affects the subsequent management and outcome of clubfoot deformity. The importance of bracing should be reinforced to parents. Bracing until at least age 4 years may be beneficial. For patients whose families are especially resistant to brace use and for older patients who experience a second relapse, regaining correction of the deformity via cast treatment followed by an Achilles lengthening procedure and/or tendon transfer may be the best alternative.