Kyriacos A. Athanasiou

This work aims to constructively use the differences between physics, as a typical representative branch of science, and biology, to enhance science education. It advocates for the use of a common science, technology, engineering, and mathematics teaching framework as a pedagogical tool for conveying concepts related to the epistemology of these two disciplines, highlighting their epistemological distinctions. Notable disparities include the absence of “universal” laws in biology, combined with the presence of a unifying theory in its instruction. Additionally, the differing roles of experimentation, mathematics, and history in these fields are examined. The text also addresses the distinction between the concepts of “social implications” and “social science,” alongside a discussion of essentialism in physics compared to the non-typological “population perspective” in biology, where the constant interplay of random errors and mutations serves as the universal driving force behind all biological phenomena.

Successful translation of allogeneic tissue-engineered neocartilage requires abundant functional cells. Human costal cartilage is a promising cell source, yet the effects of donor variability and extensive passaging remain unexplored. Therefore, this study investigated the functional (i.e. morphological, histological, mechanical, and biochemical) properties of hyaline-like neocartilage generated from high-passage human costochondral cells. A cell banking system was applied to seven donors to create master cell banks and subsequently working cell banks to fabricate P5 and P9 constructs using the processes of conservative chondrogenic passaging, aggregate rejuvenation, and self-assembly. Cell morphology or gene expression levels of these cells were correlated with mechanical and biochemical properties to identify predictive markers of neocartilage functional properties. Cells from younger donors (⩽3 months) expanded 8.7-fold more than cells from older donors (9–14 years). Cumulative expansion factors from P0 reached 3124-17397 at P5 and 1.4-36.2 million at P9. Aggregate rejuvenation was as effective at P9 as at P5 in restoring a hyaline cartilage-like phenotype, evidenced by increased cell circularity, upregulation of chondrogenic genes (e.g. >310-fold for ACAN; >200 000-fold for COL2A1; >2500-fold for Chm-1), and robust neocartilage functional properties. At P5, one young donor exhibited the highest functional properties (e.g. aggregate modulus = 310 kPa, Young’s modulus = 2.9 MPa, GAG/ww = 9.5%, COL/ww = 3.1%). At P9, a different young donor had the highest functional properties (e.g. aggregate modulus = 220 kPa, Young’s modulus = 2.3 MPa, GAG/ww = 8.6%, COL/ww = 3.4%). Gene expression levels after aggregate rejuvenation were identified to be predictive of neocartilage functional properties. For example, ACAN, Chm-1, and MIA positively correlated with Young’s modulus, ultimate tensile strength (UTS), and GAG/dw, with Chm-1 also correlating with shear modulus. SOX9 correlated with Young’s modulus and GAG/dw, while MMP13 inversely correlated with UTS and GAG/dw. These findings support the translational potential of extensively passaged human costochondral cells, the need for donor screening, and the utility of gene expression markers to predict neocartilage functional properties.

Η εισήγηση συνιστά προσπάθεια εποικοδομητικής χρήσης των διαφορών ανάμεσα στις λοιπές Φυσικές Επιστήμες (ΦΕ), με αιχμή του δόρατος τη Φυσική, και την Βιολογία (ΒΕ). Πιο συγκεκριμένα, ενθαρρύνεται το κοινό πλαίσιο της διδασκαλίας STEM ως διδακτικό εργαλείο για την διδασκαλία εννοιών σχετικών και με την επιστημολογία των δύο κλάδων, μέσω των επιστημολογικών διαφορών τους. Ως τέτοιες, προτείνονται: Η ύπαρξη ενοποιητικής θεωρίας στη διδασκαλία των ΒΕ καθώς και η απουσία «παγκόσμιων» νόμων ή ο ρόλος του πειράματος, των μαθηματικών και της Ιστορίας. Επιπλέον, συζητείται η κατανόηση των εννοιών «Κοινωνικές Προεκτάσεις» και «Κοινωνική Επιστήμη», καθώς και η ουσιοκρατία στη Φυσική, σε αντιδιαστολή με την μη-τυπολογική, «πληθυσμιακή οπτική», όπου τα συνεχή τυχαία λάθη και οι αποκλίσεις (μεταλλάξεις) στις ΒΕ συνιστούν τον κινητήριο μοχλό.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue’s stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without “packing foam–like” extracellular matrix.

The work is part of a larger project of teaching interdisciplinary teaching of physics concepts in biology within the science education class. It concerns the application of a thought experiment (ThE) about the movement of water in tracheophytes under different gravity conditions, i.e., the behavior of plants on another planet, for example the Moon or Mars. The ThE was designed and implemented in a science class of 25 students who were instructed to perform it in a simulation environment using a software file that we created with the help of Interactive Physics software. The evaluation of the ThE carried out with a written questionnaire showed that the use of such educational procedures can significantly help students to better understand the concepts related to capillary phenomena, the way water is transported to plants from roots to leaves and, generally, to contribute to the interdisciplinary teaching of physics concepts in modules related to the teaching of biological phenomena and functions.

Toward the translation of allogeneic cell therapy products, cell banks are needed not only to manufacture the final human product but also during the preclinical evaluation of an animal-based analogous cellular product (ACP). These cell banks need to be established at both the master cell bank (MCB) level and the working cell bank (WCB) level. Inasmuch as most of the development of cell therapy products is at academic centers, it is imperative that academic researchers understand how to establish MCBs and WCBs within an academic environment. To illustrate this process, using articular cartilage as the model, a cell bank for an ACP was developed (MCBs at passage 2, WCBs at passage 5) to produce self-assembled neocartilage for preclinical evaluation (constructs at passage 7). The cell bank system is estimated to be able to produce between 160 000 and 400 000 constructs for each of the six MCBs. Overall, the ACP cell bank yielded constructs that are analogous to the intended human product, which is critical toward conducting preclinical evaluations of the ACP for inclusion in an Investigational New Drug application to the FDA.