In silico modeling the potential clinical effect of growth factor treatment on the metabolism of human nucleus pulposus cells.

Background: While growth factors have the potential to halt degeneration and decrease inflammation in animal models, the literature investigating the effect of dosage on human cells is lacking. Moreover, despite the completion of clinical trials using growth differentiation factor-5 (GDF-5), no results have been publicly released.

Aims: The overall objective was to quantitatively assess the effect of three clinically relevant concentrations of GDF-5 (0.

Development and characterization of antacid microcapsules to buffer the acidic intervertebral disc microenvironment.

During intervertebral disc (IVD) degeneration, microenvironmental challenges such as decreasing levels of glucose, oxygen, and pH play crucial roles in cell survival and matrix turnover. Antacids, such as Mg(OH) and CaCO, entrapped in microcapsules are capable of neutralizing acidic microenvironments in a controlled fashion and therefore may offer the potential to improve the acidic niche of the degenerated IVD and enhance cell-based regeneration strategies. The objectives of this work were, first, to develop and characterize antacid microcapsules and assess their neutralization capacity in an acidic microenvironment and, second, to combine antacid microcapsules with cellular microcapsules in a hybrid gel system to investigate their neutralization effect as a potential therapeutic in a disc explant model.

Preclinical to clinical translation for intervertebral disc repair: Effects of species-specific scale, metabolism, and matrix synthesis rates on cell-based regeneration.

Background: A significant hurdle for potential cell-based therapies is the subsequent survival and regenerative capacity of implanted cells. While many exciting developments have demonstrated promise preclinically, cell-based therapies for intervertebral disc (IVD) degeneration fail to translate equivalent clinical efficacy.

Aims: This work aims to ascertain the clinical relevance of both a small and large animal model by experimentally investigating and comparing these animal models to human from the perspective of anatomical scale and their cellular metabolic and regenerative potential.

Harmonization and standardization of nucleus pulposus cell extraction and culture methods.

Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

Two- and three-dimensional in vitro nucleus pulposus cultures: An in silico analysis of local nutrient microenvironments.

Background: It is well established that the unique biochemical microenvironment of the intervertebral disc plays a predominant role in cell viability and biosynthesis. However, unless the effect of microenvironmental conditions is primary to a study objective, in vitro culture parameters that are critical for reproducibility are both varied and not routinely reported.

Aims: This work aims to investigate the local microenvironments of commonly used culture configurations, highlighting physiological relevance, potential discrepancies, and elucidating possible heterogeneity across the research field.

Rat tail models for the assessment of injectable nucleus pulposus regeneration strategies.

Back pain is a global epidemiological and socioeconomic problem often associated with intervertebral disc degeneration; a condition believed to initiate in the nucleus pulposus (NP). There is considerable interest in developing early therapeutic interventions to target the NP and halt degeneration. Rat caudal models of disc degeneration have demonstrated significant utility in the study of disease progression and its impact on tissue structure, composition, and mechanical performance.

Spatial patterning of phenotypically distinct microtissues to engineer osteochondral grafts for biological joint resurfacing.

Modular biofabrication strategies using microtissues or organoids as biological building blocks have great potential for engineering replacement tissues and organs at scale. Here we describe the development of a biofabrication strategy to engineer osteochondral tissues by spatially localising phenotypically distinct cartilage microtissues within an instructive 3D printed polymer framework. We first demonstrate that immature cartilage microtissues can spontaneously fuse to form homogeneous macrotissues, and that combining less cellular microtissues results in superior fusion and the generation of a more hyaline-like cartilage containing higher levels of sulphated glycosaminoglycans and type II collagen.

Consolidating and re-evaluating the human disc nutrient microenvironment.

Background: Despite exciting advances in regenerative medicine, cell-based strategies for treating degenerative disc disease remain in their infancy. To maximize the potential for successful clinical translation, a more thorough understanding of the in vivo microenvironment is needed to better determine and predict how cell therapies will respond when administered in vivo.

Aims: This work aims to reflect on the in vivo nutrient microenvironment of the degenerating IVD through consolidating what has already been measured together with investigative in silico models.

Investigating the physiological relevance of ex vivo disc organ culture nutrient microenvironments using in silico modeling and experimental validation.

Background: Ex vivo disc organ culture systems have become a valuable tool for the development and pre-clinical testing of potential intervertebral disc (IVD) regeneration strategies. Bovine caudal discs have been widely selected due to their large availability and comparability to human IVDs in terms of size and biochemical composition. However, despite their extensive use, it remains to be elucidated whether their nutrient microenvironment is comparable to human degeneration.