Traditional destructive tests are used for quality assurance and control within manufacturing workflows. Their applicability to biomanufacturing is limited due to inherent constraints of the biomanufacturing process. To address this, photo-and acoustic-based nondestructive testing has risen in prominence to interrogate not only structure and function, but also to integrate quantitative measurements of biochemical composition to cross-correlate structural, compositional, and functional variances. We survey relevant literature related to single-mode and multimodal nondestructive testing of soft tissues, which adds numbers (quantitative measurements) to pictures (qualitative data). Native and tissue-engineered articular cartilage is highlighted because active biomanufacturing processes are being developed. Included are recent efforts and prominent trends focused on technologies for clinical and in-process biomanufacturing applications.
Nondestructive testing of soft tissuesNondestructive (see Glossary) qualitative and quantitative assessment of native and tissueengineered soft tissues is a research area with great clinical and industrial potential. Specific to the biomanufacturing of tissue-engineered medical products (TEMPs), a core challenge of the field is in understanding and assessing the critical quality attributes of engineered tissues and correlating the critical process parameters and material attributes that greatly affect the intended clinical function [1]. Therefore, there is a growing need to develop nondestructive and noninvasive quantitative tools and methods to verify and to validate the critical biochemical components of TEMPs produced from a biological source, monitor extracellular matrix (ECM) development and composition, and correlate these critical components to tissue function (continuously and at predefined timepoints) [1].For example, when developing TEMPs for articular cartilage (AC), the mechanical properties (function) of native tissue are used to qualify the robustness and project the long-term efficacy of developing and clinically used products [2]. One method of tissue engineering AC is using the self-assembling process, where mature chondrocytes are harvested, dedifferentiated, and subsequently redifferentiated in vitro to produce a more hyaline-like AC [3][4][5]. Tissue engineering is inherently time-, resource-, and cost-intensive, and the destructive testing used to verify and validate tissue-engineered AC can be inappropriate or impractical for scale-up and biomanufacturing. Therefore, nondestructive methods to assess the evolution of mechanical properties and correlate them back to structure and composition are needed to further the clinical translation of TEMPs.The structure and composition of tissues has been independently evaluated by linear and nonlinear optics-based imaging techniques (e.g., second-harmonic generation (SHG) [6][7][8][9], Highlights Optics-based nondestructive techniques have shown to produce corroborative and congruent results to traditional tests.