Smith, K. W. Y. | Search bioRxiv

bioRxiv2025

Decellularized Meniscus (MEND) as a biomaterial that supports stem cell invasion and chondrogenesis

BACKGROUNDCartilage damage affects 25 million people globally each year. Tissue engineering strategies such as microfracture and matrix induced autologous chondrocyte implantation (MACI) are currently being used in the clinic; however, they are accompanied by their own limitations such as donor site morbidity, rapid clearance from the injury site, and extensive cost. To overcome these limitations, the tissue engineering field has shown increasing interest in the use of decellularized extracellular matrix (dECM) biomaterials due to their heightened integration with native tissue and regeneration rates. METHODSThe Gottardi Lab has developed a new dECM material sourced from porcine meniscus decellularization (MEND), in which elastin fibers are removed via enzymatic digestion, resulting in channels that can be easily recellularized. RESULTSIn this work we demonstrate that MEND can be seeded with bone-marrow derived mesenchymal stem cells (MSCs), achieving a uniform distribution of cell nuclei throughout the cross section of the scaffold. We also show that MEND retains its native structure in the presence of MSCs and can support chondrogenesis comparably to other commonly used tissue engineering materials such as methacrylated type I collagen and gelatin/hyaluronic acid hydrogels. CONCLUSIONOverall, MEND is a promising new dECM biomaterial for cartilage regeneration.

bioengineering↗

bioRxiv2022

Human cartilage progenitor cells from ear, nose, rib, and joint have a robust, stable phenotype for cartilage repair

BackgroundCartilage progenitor cells (CPCs) are a small but highly proliferative cell population that resides within cartilage. Joint cartilage CPCs have a high chondrogenic potential and superior cartilage formation characteristics; however, CPCs from other cartilage sources more accessible for translation such as ear, nose, and rib are broadly unexplored. Our study illuminates the differences between CPCs from these four cartilages, their corresponding tissue chondrocyte (CC), and bone marrow-derived mesenchymal stem cell (MSC). MethodsCPCs subtypes were isolated from pediatric cartilage via fibronectin selection, immunophenotyped by flow cytometry and compared to MSCs. Trilineage differentiation capacity was assessed via histology and qRT-PCR. Next, triiodothyronine was used to hypertrophically challenge each CPC subset and their corresponding chondrocyte population. After 28 days cartilage pellets were assessed via histology, immunohistochemistry, and qRT-PCR. FindingsEach CPC subset possessed a specific immunophenotypic signature with CD56 as a potential common marker. All CPC subsets proliferated 2-fold faster than MSCs and 4-fold faster than CCs. Additionally, CPCs had a substantially reduced propensity for osteogenic differentiation and very limited adipogenic capacity by histology and gene expression. Finally, all CPC subsets resisted the hypertrophic challenge more than the corresponding chondrocyte population marked by less collagen X secretion and downregulation of hypertrophy associated genes. InterpretationCPCs represent a promising cell type for cartilage regeneration. The ease of accessibility of the ear and nose CPCs present opportunities for new translational approaches and reduced clinical timelines. FundingCHOP Research Institute, Frontier Program in Airway Disorders of CHOP, NIH (R21HL159521), NSF-GRFP (DGE-1845298)

bioengineering↗