Biology subjects

McCabe, M. C.

Publications and source records attributed to McCabe, M. C..

At least 19 recordsLinked to original sources

bioRxiv2026

Compartment-Resolved Matrisome Shifts During Postnatal Tendon Maturation in Mice

Tendons acquire their load-bearing capacity during the first month of postnatal growth, driven by the extensive remodeling of the extracellular matrix (ECM). While the role of specific individual components to this process have been well characterized, a comprehensive assessment of how the tendon matrisome changes during this critical window is lacking. This, in part, is due to the challenges associated with solubilization of mature ECM, which is underrepresented by conventical proteomic approaches. To address this, we performed compartment-resolved proteomics on murine Achilles and plantaris tendons at postnatal days 0 (P0), P14, and P28. Sequential extraction methods leveraged a CHAPS-soluble fraction, capturing cellular and soluble matrisome proteins, from the insoluble mature ECM fraction, solubilized by guanidine hydrochloride and hydroxylamine hydrochloride and separately analyzed by label-free quantitative LC-MS/MS. Analysis shows that the two compartments followed distinct trajectories during maturation. The insoluble matrix was dominated by collagenous proteins, which increased from 95% to over 99% of the identified signal intensity, and its composition was largely established by P14. Within the soluble matrisome compartment, collagens increased from 50% to over 60% by P14, accompanied by dynamic regulation of proteins implicated in collagen processing (P4HA1, PCOLCE), crosslinking (LOX, LOXL2), and regulators of collagen fibril assembly and growth (DCN, BGN, FMOD, THBS3, THBS4). Beyond these established regulators, we observed dynamic regulation of less-characterized fibril-associated proteoglycans (KERA, OGN, CHAD), matricellular (COMP, POSTN, MATN2), and angiogenic regulatorily proteins (SERPINF1, ECM1). Together, this work establishes a comprehensive protein-level reference for postnatal tendon maturating, provides new insights into the molecular regulation of functional tendon development.

developmental biology↗

bioRxiv2026

Translating Sex- and Disease-Informed Design Criteria from Human Lung into Engineered Biomaterials

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by pathological extracellular matrix (ECM) remodeling, and a pronounced sex disparity, with approximately 70% of cases occurring in males. Despite these differences, biomaterials used to model fibrosis are commonly designed to replicate disease state or stiffness alone and rarely account for biological sex. Here, we derived sex- and disease-informed biomaterial design criteria from female and male control and IPF human lungs and translated these criteria into engineered hybrid-hydrogels containing human lung decellularized ECM (dECM) and poly(ethylene glycol) alpha methacrylate (PEGMA). Matrisome-focused reanalysis of our previously published region-resolved human lung proteomic dataset revealed region- and sex-associated differences in fibrillar collagens, matricellular proteins, and structural proteoglycans. Complementary characterization of human lung tissue further identified sex- and disease-associated differences in fibrillar collagen architecture, proteoglycan and glycosaminoglycan (GAG) remodeling, and tissue mechanics. Male IPF lungs exhibited the highest levels of disease-associated stiffening and fibrillar collagen remodeling, while female IPF tissue showed comparatively modest mechanical changes despite biochemical remodeling. These measurements established tissue-informed design criteria spanning matrix composition, architecture, and mechanics. We next evaluated whether tissue-derived properties were reproduced or retained following decellularization, processing, and incorporation of donor-derived dECM into hybrid-hydrogels. Engineered hybrid-hydrogels closely recapitulated sex- and disease-associated mechanical relationships, while COL1A1-associated abundance patterns were more consistently preserved than fibrillar collagen organization. Matricellular proteins and GAG-rich matrix remained detectable, although condition-dependent biochemical fidelity varied. This work establishes a human tissue-informed framework for engineering sex- and disease-specific biomaterials, highlighting the importance of defining sex-associated ECM properties and validating individual features following material fabrication to advance human models of IPF and other diseases with sex-associated differences in susceptibility and progression.

bioengineering↗

bioRxiv2026

Extracellular matrix context shapes morphogenesis and lactation-associated states in human milk-derived mammary organoids

The mammary gland relies on reciprocal interactions between epithelial cells and their surrounding extracellular matrix (ECM) to form and maintain milk-producing tissue structures. Yet these processes remain difficult to study in human model systems. Mammary epithelial cells (MECs) can be isolated noninvasively from breast milk, but whether they generate three-dimensional organoids and respond to matrix cues has been unclear. Here, human milk-derived MECs (milk MECs) spontaneously form complex organoids, including polarized acinar and terminal duct lobular unit-like structures after isolation. To investigate how matrix composition shapes these organoids, milk MECs were cultured in decellularized mammary ECM (dECM), Matrigel, and collagen I. In dECM, milk MECs formed polarized branched networks with aligned actin organization along collagen fibrils, whereas in Matrigel they adopted a more lactation-associated state, marked by {beta}-casein expression and milk fat globules. Together, these findings establish breast milk-derived MEC organoids as a human model to study how ECM context regulates mammary morphogenesis and lactation biology.

cell biology↗

bioRxiv2026

Distinct extracellular matrix states uncouple collagen accumulation from pathological fibrosis in Duchenne muscular dystrophy

Fibrosis severity is routinely inferred from collagen abundance, although whether collagen quantity determines pathological fibrosis remains unclear. In Duchenne muscular dystrophy (DMD), chronic muscle injury and inflammation drive extracellular matrix accumulation, making these processes difficult to disentangle. We exploit sarcospan overexpression in mdx mice, a model of DMD (mdxTG), which improves membrane integrity and muscle function despite persistent matrix remodeling. mdxTG muscle accumulates more collagen than mdx yet lacks its dense macrophage-rich scars. Matrisome proteomics and spatial transcriptomics reveal compositionally and spatially distinct matrix states, while decellularized mdxTG matrix protects myotubes from membrane damage relative to mdx matrix. Despite these differences, both dystrophic matrices remain stiff and induce nuclear YAP in fibro-adipogenic progenitors. Verteporfin suppresses collagen production and reduces fibrosis in vivo, while nuclear YAP is increased in FAPs from patients with DMD. Thus, collagen abundance alone does not define pathological fibrosis; matrix organization, biological activity, and mechanosignaling distinguish functionally distinct fibrotic states.

physiology↗

bioRxiv2026

Particle-Only gECM Wafers Enable Cohesive, ECM-Rich Scaffolds Without Secondary Polymers

Granular extracellular matrix (gECM)-based biomaterials commonly contain polymer components to improve scaffold cohesion and handling during fabrication and use. However, these polymer hydrogel components may dilute ECM content and increase fabrication and regulatory complexity. This study evaluated whether particle-only gECM wafers could serve as a simplified alternative to hydrogel-based gECM scaffolds while maintaining structural, mechanical, and biological performance. Decellularized human cartilage and skin tissues were processed and fabricated into three scaffold formats: gECM hydrogels, freeze-dried gECM hydrogel wafers, and freeze-dried particle-only gECM wafers. Across fabrication methods, scaffold swelling, volume fraction, and stiffness were strongly influenced by both tissue type and fabrication approach. gECM hydrogels exhibited the greatest swelling and lowest stiffness, while gECM wafers displayed higher volume fractions and greater mechanical stiffness. Notably, gECM particle-only wafers achieved performance comparable to gECM hydrogel wafers despite the absence of a secondary polymer network. Particle-only wafers also maintained swelling behavior and structural properties over 3 months of dry storage at room temperature, with only modest decreases in stiffness. In vitro studies showed sustained cell viability over 14 days on particle-only wafers, with chondrocytes infiltrating cartilage wafers and fibroblasts remaining primarily surface-localized on skin wafers. In addition, particle-only wafers remained cohesive during implantation into a bovine cartilage defect model. These findings demonstrate that particle-only gECM wafers can achieve structural integrity, mechanical performance, and cytocompatibility without the need for an additional polymer network, highlighting a simplified and ECM-rich biomaterial platform. By eliminating polymer carriers and enabling dry storage with preserved function, this approach supports the development of off-the-shelf, translationally accessible gECM particle-only wafers for tissue engineering applications.

bioengineering↗

bioRxiv2026

Human Osteochondral Granular Extracellular Matrix (gECM) Hydrogels Drive Tissue-Specific Composition and Mechanics

Osteochondral defects remain a major clinical challenge due to the limited regenerative capacity of cartilage and the complexity of the osteochondral interface. Here, we present a human-derived granular extracellular matrix (gECM) hydrogel platform designed for translational osteochondral repair. Using otherwise discarded human donor tissues, we developed cartilage and bone gECM hydrogels under current good manufacturing practice workflows. These materials are shear-thinning, immediately hold their form, and crosslink under physiological conditions to form stable constructs. Proteomic analysis confirmed that cartilage and bone gECM retain distinct tissue-specific biochemical signatures, while mechanical characterization demonstrated tissue-relevant stiffness, with bone gECM hydrogels exhibiting greater stiffness than cartilage gECM hydrogel. Particle packing density primarily governed viscosity, whereas tissue type contributed strongly to bulk stiffness. Together, these findings establish a scalable, human-derived gECM platform that integrates tissue-specific structural and mechanical cues, and advances a clinically translatable strategy for osteochondral repair.

bioengineering↗

bioRxiv2026

Proteomic analysis reveals regional sex differences in healthy and fibrotic human lung

Biological sex has systemic effects on gene expression, cell behavior, and disease etiology. Despite these widespread effects, sex as a biological variable is understudied, particularly in chronic lung diseases. In idiopathic pulmonary fibrosis (IPF), 70% of patients are male, and male patients have overall worse survival post-diagnosis. While behavioral differences between sexes might account for some of the epidemiological differences, the contribution of underlying biology is not known. In this study, we performed regional proteomic analysis via laser-captured microdissection-coupled mass spectrometry and analyzed the data for sex-biased protein expression. We discovered that even in control lung, sex differences existed in both airway and alveolar regions. Sex differences became more pronounced in diseased regions, with sex-biased expression of diverse proteins including those involved in extracellular vesicle secretion, cellular metabolism, and extracellular matrix remodeling. These data suggest that baseline sex differences in lung proteome may contribute to sex-specific susceptibility, progression, and clinical outcomes in IPF, underscoring the need for future mechanistic and clinical studies to account for sex as a biological variable.

bioengineering↗

bioRxiv2026

Granular Extracellular Matrix (gECM) Hydrogels Enable Distinct Composition and Mechanics Across Tissue Types for Translation

Biomaterials-based tissue engineering aims to recapitulate native tissue architecture and function for both clinical repair and advanced in vitro models. While improvements in biomaterials have been made, including granular hydrogels and ECM-derived scaffolds, current biomaterials lack intentional design choices for effective translation, including regulatory considerations, practical extrusion delivery, and biomimetic characteristics. Here, we develop and characterize a library of granular ECM (gECM) biomaterials for five key tissues (cartilage, bone, skin, liver, and kidney), in which ECM particles are densely packed within a hyaluronic acid hydrogel. We optimize tissue processing methods that preserve proteomic content and structure while also aligning with scale-up manufacturing and regulatory guidelines. We show that gECM hydrogels can be molded, extruded, and 3D-printed while retaining their shape, and they stabilize at physiological temperature and pH. Lastly, we demonstrate that bulk gECM mechanics are driven by tissue type, and gECM hydrogels support viability, proliferation, and tissue-specific cellular activity. Together, these findings establish gECM hydrogels as a translational and biomimetic platform for clinical tissue repair and complex in vitro models.

bioengineering↗

bioRxiv2026

Flowable Grafts Made from Granular Extracellular Matrix (gECM) Hydrogels Promote Integrative Repair of Articular Cartilage in a Large-Animal Model

Focal injuries to articular cartilage in load-bearing joints fail to heal and often progress to degeneration, underscoring the need for repair strategies that result in restored cartilage structure and function rather than fibrocartilage formation. Granular extracellular matrix (gECM) hydrogels, flowable grafts composed of densely-packed matrix particles, offer a promising approach but lack long-term functional validation in large-animal models. Here, we developed a flowable gECM hydrogel composed of decellularized cartilage microparticles incorporated within a thiol-functionalized hyaluronan matrix. Proteomic analysis confirmed enrichment of cartilage-specific gECM matrisome components. When implanted into critical-sized femoral condyle defects in a goat model and evaluated 12 months post-implantation, both gECM hydrogel and microdrilling (surgical controls) achieved >80% defect filling. However, in contrast to microdrilling, gECM repair tissue exhibited surface tribological (friction, adhesion) and compressive mechanical properties comparable to native cartilage, with a similar proteoglycan-to-collagen ratio, enrichment of type II collagen, minimal type I collagen (typical of a fibrous scar), improved quantitative MRI metrics, and evidence of lateral cartilage integration and subchondral bone remodeling. Together, these findings demonstrate that a flowable gECM hydrogel supports integrative, cartilage-like repair in a load-bearing joint, supporting advancement of this approach toward clinical translation. One Sentence SummaryA granular ECM hydrogel implanted in a goat condyle provided a robust repair, filling the defect tissue with integrated, hyaline-like cartilage at 12 months.

bioengineering↗

bioRxiv2026

A Candida glabrata adhesin-like effector drives fitness and immunogenicity in the gut

Candida glabrata is a leading cause of invasive candidiasis. The gut serves as its primary reservoir, yet factors governing colonization and pathogenic potential remain poorly defined. Here, we identify immunoglobulin A (IgA) as a key regulator of C. glabrata within the intestinal microbiome. We found that C. glabrata induces an IgA response in a strain-specific manner. Comparative transcriptional and proteomic analyses of IgA-inducing and non-inducing strains identified a putative adhesin, Awp11, whose expression correlated with IgA induction. Awp11 is directly targeted by IgA and is required for inducing C. glabrata-specific IgA and Th17 responses in vivo. Functionally, Awp11 promotes colonization of a complex intestinal microbiome, and intestinal IgA limits this advantage. In most strains, AWP11 transcription is dynamic and limited by IgA in the gut. This identifies Awp11 as a key determinant of strain-dependent immunogenicity and gut colonization that C. glabrata may dynamically regulate to balance colonization and immune evasion.

immunology↗

bioRxiv2025

An infusible decellularized extracellular matrix material binds to vasculature in infarcted myocardium and induces pro-reparative gene expression following acute myocardial infarction through inherent avidity and bioactive signaling

To treat acute myocardial infarction immediately after reperfusion, we previously engineered an intravascularly infusible decellularized extracellular matrix (iECM) biomaterial that exerts immunomodulatory and pro-reparative effects. However, the impact of the heterogeneous contents of iECM on infarct localization and downstream biological function is unknown. Using liquid chromatography, iECM is separated into a high molecular weight (MW) and low MW component. Mass spectrometry confirms compositional similarity, while biochemical assays and transmission electron microscopy highlight differences in biochemical features and structure, revealing a nanofibrillar high MW component and a globular peptide low MW. Quartz crystal microbalance studies show binding of each component to basal lamina ECM proteins and endothelial cell surface receptors under flow, demonstrating the specificity of ECM biomaterials to permeable vasculature. In vivo, the low MW component reduces vascular permeability, while neither component alone achieves the retention levels of complete iECM. Using single-nucleus RNA sequencing to probe bioactivity, both components elicited comparable angiogenic, immunomodulatory, and pro-reparative transcriptional programs. These findings illustrate that highly coupled materials and biological characterization uncover fundamental behaviors and properties of iECM biomaterials. Additionally, we show the unique binding behavior of iECM to the gaps of permeable vasculature, which could be exploited for future nanomaterial design.

bioengineering↗

bioRxiv2025

Volumetric printed biomimetic scaffolds support in vitro lactation of human milk-derived mammary epithelial cells

The human breast is remarkably plastic and remodels with each birth to produce milk optimally suited for the changing demands of the newborn. This dynamic nature of lactation makes it challenging to study under controlled conditions. Given the health benefits of human milk, models of secretory mammary tissue would offer new opportunities to study factors that influence this important food source. First, 3D models of the mammary duct/alveoli (D/A) were designed based on shapes found in vivo. Photoresins based on mammary decellularized extracellular matrix (dECM) were optimized to match the mechanical properties of native breast tissue. Next, these dECM-based D/A models were printed with a volumetric printer and seeded with human milk-derived mammary epithelial cells (MECs). MECs formed stable epithelial layers on the printed surfaces and secreted the beta-casein and milk-fat-globules. This novel model offers exciting avenues to explore hormonal, nutritional, and mechanobiological factors involved in lactation, thereby improving understanding of lactation for the benefit of infant and their mothers.

bioengineering↗

bioRxiv2024

Discerning Specific Thrombolytic Activities and Blood Clot Degradomes of Diverse Snake Venoms with Untargeted Peptidomics

Identification and characterization of snake venom toxins that interfere with hemostasis have important implications for the treatment of snake envenomation, the bioprospecting of therapeutically useful molecules, and the development of research tools for investigating hematologic disorders. Many venoms have been shown to possess thrombolytic activity. However, it remains unclear if actions on other clot-stabilizing proteins beyond fibrin chains contribute significantly to venom-induced thrombolysis because the clot-wide targets of venom proteases and the mechanisms responsible for thrombolysis are not well understood. Here, we utilize a high-throughput time-based thrombolysis assay in combination with untargeted peptidomics to provide comprehensive insight into the effects of venom from six snake species on blood clot degradation. We compare thrombolytic profiles across venoms with variable levels of proteases and generate venom-specific fingerprints of cleavage specificity. We also compare the specific effects of venoms that possess a range of thrombolytic activity on fibrin subunits and other clot-bound proteins involved in clot structure. Venoms with higher thrombolytic activity demonstrated an enhanced ability to target multiple sites across fibrin chains critical to clot stability and structure, as well as clot-stabilizing proteins including fibronectin and vitronectin. Collectively, this study significantly expands our understanding of the thrombolytic and fibrinolytic effects of snake venom by determining the full suite of clot-specific venom targets that are involved in clot formation and stability.

pharmacology and toxicology↗

bioRxiv2024

Anisotropic Articular Cartilage Biofabrication based on Decellularized Extracellular Matrix

Tissue-engineered grafts that mimic articular cartilage show promise for treating cartilage injuries. However, engineering cartilage cell-based therapies to match zonal architecture and biochemical composition remains challenging. Decellularized articular cartilage extracellular matrix (dECM) has gained attention for its chondro-inductive properties, yet dECM-based bioinks have limitations in mechanical stability and printability. This study proposes a rapid light-based bioprinting method using a tyrosine-based crosslinking mechanism, which does not require chemical modifications of dECM and thereby preserves its structure and bioactivity. Combining this resin with Filamented Light (FLight) biofabrication enables the creation of cellular, porous, and anisotropic dECM scaffolds composed of aligned microfilaments. Specifically, we investigate the effects of various biopolymer compositions (i.e., hyaluronic acid, collagen I, and dECM) and inner architecture (i.e., bulk light vs FLight) on immune response and cell morphology, and we investigate their influence on nascent ECM production and long-term tissue maturation. Our findings highlight the importance of FLight scaffolds in directing collagen deposition resembling articular cartilage structure and promoting construct maturation, and they emphasize the superiority of biological-rich dECM over single-component materials for engineering articular cartilage, thereby offering new avenues for the development of effective cartilage tissue engineering strategies.

bioengineering↗

bioRxiv2024

Assessing Heterogeneity in the N-Telopeptides of Type I Collagen by Mass Spectrometry

Collagen cross-links created by the lysyl oxidase and lysyl hydroxylase families of enzymes are a significant contributing factor to the biomechanical strength and rigidity of tissues, which in turn influence cell signaling and ultimately cell phenotype. In the clinic, the proteolytically liberated N-terminal cross-linked peptide of collagen I (NTX) is used as a biomarker of bone and connective tissue turnover, which is altered in several disease processes. Despite the clinical utility of these collagen breakdown products, the majority of the cross-linked peptide species have not been identified in proteomic datasets. Here we evaluate several parameters for the preparation and identification of these peptides from the collagen I-rich Achilles tendon. Our refined approach involving chemical digestion for protein solubilization coupled with mass spectrometry allows for the identification of the NTX cross-links in a range of modification states. Based on the specificity of the enzymatic cross-linking reaction we utilized follow-up variable modification searches to facilitate identification with a wider range of analytical workflows. We then applied a spectral library approach to identify differences in collagen cross-links in bovine pulmonary hypertension. The presented method offers unique opportunities to understand extracellular matrix remodeling events in development, aging, wound healing, and fibrotic disease that modulate collagen architecture through lysyl-hydroxylase and lysyl-oxidase enzymes.

biochemistry↗

bioRxiv2023

PDGFRα/β heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation

The platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases allows cells to communicate with one another by binding to growth factors at the plasma membrane and activating intracellular signaling pathways to elicit responses such as migration, proliferation, survival and differentiation. The PDGFR family consists of two receptors, PDGFR and PDGFR{beta}, that dimerize to form PDGFR homodimers, PDGFR/{beta} heterodimers and PDGFR{beta} homodimers. Here, we overcame prior technical limitations in visualizing and purifying PDGFR/{beta} heterodimers by generating a cell line stably expressing C-terminal fusions of PDGFR and PDGFR{beta} with bimolecular fluorescence complementation fragments corresponding to the N-terminal and C-terminal regions of the Venus fluorescent protein, respectively. We found that these receptors heterodimerize relatively quickly in response to PDGF-BB ligand treatment, with a peak of receptor autophosphorylation following 5 minutes of ligand stimulation. Moreover, we demonstrated that PDGFR/{beta} heterodimers are rapidly internalized into early endosomes, particularly signaling endosomes, where they dwell for extended lengths of time. We showed that PDGFR/{beta} heterodimer activation does not induce downstream phosphorylation of ERK1/2 and significantly inhibits cell proliferation. Further, we characterized the PDGFR dimer-specific interactome and identified MYO1D as a novel protein that preferentially binds PDGFR/{beta} heterodimers. We demonstrated that knockdown of MYO1D leads to retention of PDGFR/{beta} heterodimers at the plasma membrane, resulting in increased phosphorylation of ERK1/2 and increased cell proliferation. Collectively, our findings impart valuable insight into the molecular mechanisms by which specificity is introduced downstream of PDGFR activation to differentially propagate signaling and generate distinct cellular responses. One-sentence summaryPDGFR/{beta} heterodimer binding to MYO1D contributes to rapid internalization of the dimerized receptors, thereby negatively affecting downstream ERK1/2 signaling and cellular proliferation.

cell biology↗

bioRxiv2023

ASSESSING TARGET SPECIFICITY OF THE SMALL MOLECULE INHIBITOR MARIMASTAT TO SNAKE VENOM TOXINS: A NOVEL APPLICATION OF THERMAL PROTEOME PROFILING

New treatments that circumvent the pitfalls of traditional antivenom therapies are critical to address the problem of snakebite globally. Numerous snake venom toxin inhibitors have shown promising cross-species neutralization of medically significant venom toxins in vivo and in vitro. The development of high-throughput approaches for the screening of such inhibitors could accelerate their identification, testing, and implementation, and thus holds exciting potential for improving the treatments and outcomes of snakebite envenomation worldwide. Energetics-based proteomic approaches, including Thermal Proteome Profiling (TPP) and Proteome Integral Solubility Alteration (PISA), assays represent "deep proteomics" methods for high throughput, proteome-wide identification of drug targets and ligands. In the following study, we apply TPP and PISA methods to characterize the interactions between venom toxin proteoforms in Crotalus atrox (Western Diamondback Rattlesnake) and the snake venom metalloprotease (SVMP) inhibitor marimastat. We investigate its venom proteome-wide effects and characterize its interactions with specific SVMP proteoforms, as well as its potential targeting of non-SVMP venom toxin families. We also compare the performance of PISA thermal window and soluble supernatant with insoluble precipitate using two inhibitor concentrations, providing the first demonstration of the utility of a sensitive high-throughput PISA-based approach to assess the direct targets of small molecule inhibitors for snake venom.

biochemistry↗

bioRxiv2023

ECM-Focused Proteomic Analysis of Ear Punch Regeneration in Acomys cahirinus

In mammals, significant injury is generally followed by the formation of a fibrotic scar which provides structural integrity but fails to functionally restore damaged tissue. Spiny mice of the genus Acomys represent the first example of full skin autotomy in mammals. Acomys cahirinus has evolved extremely weak skin as a strategy to avoid predation and is able to repeatedly regenerate healthy tissue without scar after severe skin injury or full-thickness ear punches. Extracellular matrix (ECM) composition is a critical regulator of wound repair and scar formation and previous studies have suggested that alterations in its expression may be responsible for the differences in regenerative capacity observed between Mus musculus and A. cahirinus, yet analysis of this critical tissue component has been limited in previous studies by its insolubility and resistance to extraction. Here, we utilize a 2-step ECM-optimized extraction to perform proteomic analysis of tissue composition during wound repair after full-thickness ear punches in A. cahirinus and M. musculus from weeks 1 to 4 post-injury. We observe changes in a wide range of ECM proteins which have been previously implicated in wound regeneration and scar formation, including collagens, coagulation and provisional matrix proteins, and matricryptic signaling peptides. We additionally report differences in crosslinking enzyme activity and ECM protein solubility between Mus and Acomys. Furthermore, we observed rapid and sustained increases in CD206, a marker of pro-regenerative M2 macrophages, in Acomys, whereas little or no increase in CD206 was detected in Mus. Together, these findings contribute to a comprehensive understanding of tissue cues which drive the regenerative capacity of Acomys and identify a number of potential targets for future pro-regenerative therapies.

molecular biology↗