Biology subjects

McCreery, K.

Publications and source records attributed to McCreery, K..

3 recordsLinked to original sources

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↗

bioRxiv2022

Acellular Cartilage-Bone Allografts Restore Structure, Mechanics, and Surface Properties In Vivo, but Limit Recellularization and Integrative Repair

The repair of articular cartilage after damage is challenging, and clinical interventions to promote regeneration remain elusive. The most effective treatment for cartilage defects utilizes viable osteochondral allografts from young donors, but unfortunately suffers from severe source limitations and short storage time. Decellularized tissue offers the potential to utilize native tissue structure and composition while also overcoming source limitations, but the long-term efficacy of acellular allografts is unknown. Here, we show that acellular osteochondral allografts improve functional and integrative cartilage repair in defect regions after 6 months in a preclinical (sheep) animal model. Functional measures of intratissue strain and structure assessed by MRI demonstrate similar biomechanical performance between implants and native cartilage. Compared to native tissue, the structure, composition, and tribology of acellular allografts conserve surface roughness and lubrication, native cartilage material properties under compression and relaxation, and compositional ratios of collagen:glycosaminoglycan and collagen:phosphate. However, while high cellularity was observed in the integration zones between native cartilage and acellular allografts, recellularization throughout the chondral implant was largely lacking, potentially limiting long-term cellular maintenance in the graft and repair success. Our results advance a suite of joint-to-cellular functional assays, demonstrate the biomechanical efficacy of acellular allografts for at least six months in vivo, and suggest that long-term implant success may suffer from a lack of cell migration into the dense decellularized chondral tissue.

bioengineering↗

bioRxiv2020

Nuclear stiffness decreases with disruption of the extracellular matrix in living tissues

Reciprocal interactions between the cell nucleus and the extracellular matrix lead to macroscale tissue phenotype changes. The extracellular environment is physically linked to the nuclear envelope and provides cues to maintain nuclear structure and cellular homeostasis regulated in part by mechanotransduction mechanisms. However, little is known about how structure and properties of the extracellular matrix in living tissues impacts nuclear mechanics, and current experimental challenges limit the ability to detect and directly measure nuclear mechanics while cells are within the native tissue environment. Here, we hypothesized that enzymatic disruption of the tissue matrix results in a softer tissue, affecting the stiffness of embedded cell and nuclear structures. We aimed to directly measure nuclear mechanics without perturbing the native tissue structure to better understand nuclear interplay with the cell and tissue microenvironments. To accomplish this, we expanded an atomic force microscopy needle-tip probe technique that probes nuclear stiffness in cultured cells to measure the nuclear envelope and cell membrane stiffness within native tissue. We validated this technique by imaging needle penetration and subsequent repair of the plasma and nuclear membranes of HeLa cells stably expressing the membrane repair protein CHMP4B-GFP. In the native tissue environment ex vivo, we found that while enzymatic degradation of viable cartilage tissues with collagenase 3 (MMP-13) and aggrecanase-1 (ADAMTS-4) decreased tissue matrix stiffness, cell and nuclear membrane stiffness is also decreased. Finally, we demonstrated the capability for cell and nucleus elastography using the AFM needle-tip technique. These results demonstrate disruption of the native tissue environment that propagates to the plasma membrane and interior nuclear envelope structures of viable cells.

biophysics↗