Bioengineered wharton's jelly derived extracellular matrix
Inventors
Aljitawi, Omar • Awad, Hani • Becker, Michael
Assignees
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Publication Number
US-12472282-B2
Publication Date
2025-11-18
Expiration Date
Abstract
The present invention provides bioengineered extracellular matrix model derived from decellularized Wharton's jelly matrix (DWJM) and methods for making and using the same. After decellularization, the DWJM is homogenized, frozen, and lyophilized in a mold to form a molded scaffold having a substantially uniform pore size, pore distribution, and matrix component distribution, and can be trimmed and shaped to any desired size. The bioengineered DWJM is able to maintain the stem cell qualities of cultured cells, which is useful in screening chemotherapy drugs that target cancers, especially cancer stem cell populations. The bioengineered DWJM possesses matrix components similar to the bone hematopoietic niche and is useful in expanding and maintaining hematopoietic stem cells as well as promoting bone regeneration and repair.
Core Innovation
The invention relates to a porous matrix comprising molded homogenized decellularized Wharton’s jelly matrix (DWJM). The matrix has a median pore size between about 200 μm and about 350 μm, and a pore size distribution that is no more than 50% or 17% of the median pore size. The described structure provides a substantially uniform three-dimensional scaffold with defined pore properties.
In the described bioengineered scaffold, DWJM is homogenized, frozen, lyophilized, and molded into a desired format, such as sheets or disks. The scaffold is characterized by defined pore size distribution deviation limits and by volumetric porosity of about 80–95%. The matrix is further described as having a homogeneous distribution of specified extracellular matrix components, including collagen, fibronectin, TN-C, and HA.
The invention further describes using the molded porous DWJM scaffold for cellular and biomedical models, including maintaining hematopoietic stem cell qualities for hematopoietic stem cell expansion and quiescence, including CD34+ cells and megakaryocyte-lineage bias. It also describes promoting bone regeneration via growth factor loading and creating reproducible cancer stem cell and drug-screening models, including acute myeloid leukemia (AML) models with described changes in apoptosis and cellular metabolic features.
Claims Coverage
The independent claim covers a porous molded homogenized decellularized Wharton’s jelly matrix defined by quantitative pore size and pore size distribution constraints, with dependent refinements adding additional quantitative and format features and narrowing to specific seeded-cell and growth/therapeutic uses.
Porous molded homogenized decellularized Wharton’s jelly matrix with defined pore size and pore size distribution
A porous matrix comprising molded homogenized decellularized Wharton’s jelly matrix (DWJM) having a median pore size between about 200 μm and about 350 μm, and a pore size distribution that is no more than 50% or 17% of the median pore size.
Tighter median pore size range for the porous matrix
The porous matrix has a median pore size between about 230 μm and about 330 μm.
Volumetric porosity constraint
The porous matrix has a volumetric porosity between about 80% and about 95%.
Disc shape sized for cell culture wells
The porous matrix is molded or trimmed into a disc shape sized to fit in a cell culture well.
Hematopoietic stem cell culturing with maintained quiescence using CD34+ cells
A method for culturing hematopoietic stem cells by seeding CD34+ cells onto the porous matrix, such that the cells remain quiescent during culture.
Megakaryocyte lineage bias of cultured CD34+ cells
The seeded CD34+ cells are biased toward the megakaryocyte lineage.
Overall, the claim set defines a molded homogenized DWJM porous matrix by median pore size and pore size distribution constraints, optionally refined with additional pore and structural quantitative limits and disc format, and further narrows to culturing CD34+ hematopoietic stem cells with maintained quiescence and megakaryocyte-lineage bias.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Maintaining hematopoietic stem cell qualities for hematopoietic stem cell expansion and quiescence using CD34+ cells, including megakaryocyte-lineage bias.
Bone regeneration via growth factor loading, including osteogenic and angiogenic growth factors such as BMP-2 and VEGF.
Reproducible high-throughput cancer stem cell and drug-screening models, including acute myeloid leukemia (AML) models described with reduced doxorubicin apoptosis via adherence-driven metabolic/glycolysis changes.
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