Extracellular matrix (ECM) hydrogel therapies are being developed to treat diseased or damaged tissues and organs throughout the body. Many ECM hydrogels are progressing from in vitro models to in vivo biocompatibility studies and functional models. There is significant potential for clinical translation of these therapies since one ECM hydrogel therapy is already in a Phase 1 clinical trial.

PurposeThe collagen structure of the human peripapillary sclera plays a significant role in determining optic nerve head (ONH) biomechanics, and is therefore of interest in the study of glaucoma. The aim of the current work was to map the anisotropic collagen structure of the normal human peripapillary sclera as a function of tissue depth.MethodsWide-angle x-ray scattering was used to quantify collagen fibril orientation at 0.5mm intervals across six 150μm-thick serial sections through the peripapillary sclera of eight normal European-derived human eyes. Two structural parameters were measured: 1) the relative number of fibrils preferentially aligned at a given angle within the tissue plane, 2) the degree of collagen alignment (anisotropy).ResultsThe inner-most one-third of the peripapillary scleral stroma (nearest to the choroid) was characterised by collagen fibrils either randomly arranged or preferentially aligned radially with respect to the ONH. In contrast, the outer two-thirds of the tissue was dominated by a circumferential arrangement of collagen encircling the ONH. In all tissue regions the degree of collagen anisotropy peaked in the mid-stroma and progressively decreased towards the tissue surfaces, with the largest depth variations occurring in the inferior-nasal quadrant, and the smallest occurring in the superior-nasal quadrant.ConclusionsSignificant, region-specific variations in collagen structure are present in the human peripapillary sclera as a function of depth. In normal eyes, the circumferential collagen fibril architecture is most prominent in the outer two-thirds of the stroma, possibly as a mechanical adaption to more effectively support the lamina cribrosa at the level of its insertion into the scleral canal wall.

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An optimal concentration of a decellularized skeletal muscle extracellular matrix hydrogel was eventuated for eventual clinical translation.

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SummaryA first-in-man clinical study on a myocardial-derived decellularized extracellular matrix (ECM) hydrogel yielded evidence for potential efficacy in ischemic heart failure (HF) patients. However, little is understood about the mechanism of action in chronic myocardial infarction (MI). In this study we investigated efficacy and mechanism by which the myocardial matrix hydrogel can mitigate negative left ventricular (LV) remodeling in a chronic model of MI. Assessment of cardiac function via magnetic resonance imaging (MRI) demonstrated preservation of LV volumes and apical wall thickening. Differential gene expression analyses showed the matrix is able to prevent worsening HF in a small animal chronic MI model through modulation of the immune response, downregulation of pathways involved in HF progression and fibrosis, and upregulation of genes important for cardiac muscle contraction.

This article provides an overview of a new integrated software tool for reduction and analysis of small-angle X-ray scattering (SAXS) data from fibrous collagen tissues, with some wider applicability to other cylindrically symmetric scattering systems. SAXS4COLL combines interactive features for data pre-processing, bespoke background subtraction, semi-automated peak detection and calibration. Both equatorial and meridional SAXS peak parameters can be measured, and the former can be deconstructed into cylinder and lattice contributions. Finally, the software combines functionality for determination of collagen spatial order parameters with a rudimentary orientation plot capability.

Extracellular matrix (ECM) hydrogels have been widely used in preclinical studies as injectable materials for tissue engineering therapies. We have developed a new ECM therapy, the soluble fraction derived from decellularized, digested ECM, for intravascular infusion. This new form of ECM is capable of gelation in vivo and can be delivered acutely after an injury to promote cell survival and improve vascularization. In this study, we show proof-of-concept for the feasibility, safety, and efficacy of ECM infusions using small and large animal models of acute myocardial infarction (MI) and intracoronary infusion. Following infusion, the ECM material was retained in the heart, specifically in regions of ischemia, and colocalized with endothelial cells, coating the leaky microvasculature. Functional improvements, specifically reduced left ventricular volumes, were observed after ECM infusion post-MI. Genes associated with angiogenesis were upregulated, and genes associated with cell apoptosis/necrosis and fibrosis were downregulated. The ECM was also delivered using a clinically-relevant catheter in a large animal model of acute MI. This study shows proof-of-concept for a new intravascular delivery strategy for ECM biomaterial therapies with potential implications for a variety of pathologies with ischemic tissue or injured vasculature.