Biomaterial comprising adipose-derived stem cells and method for producing the same
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Publication Number
US-11602579-B2
Publication Date
2023-03-14
Expiration Date
Abstract
The present invention relates to a biomaterial comprising adipose-derived stem cells (ASCs), a ceramic material and an extracellular matrix. In particular, the biomaterial according the present invention secretes osteoprotegerin (OPG), and comprises insulin-like growth factor (IGF1) and stromal cell-derived factor 1-alpha (SDF-1α). The present invention also relates to methods for producing the biomaterial and uses thereof.
Core Innovation
Disclosed is a scaffold-free three-dimensional biomaterial composed of autologous adipose-derived stem cells (ASCs) that are osteogenic differentiated and combined with calcium phosphate ceramic particles comprising a mixture of hydroxyapatite (HA) and beta-tricalciumphosphate (B-TCP). The scaffold-free meaning is essentially free of any exogenous extracellular matrix, while the biomaterial comprises an extracellular matrix (ECM) secreted by the ASCs. The ASCs and the HA/B-TCP particles are integrated into the ECM.
The biomaterial is characterized by secretion of osteoprotegerin (OPG), with the biomaterial secreting at least about 5 ng of osteoprotegerin (OPG) per g of biomaterial. The described secretion profile further includes aspects of growth-factor and cytokine production, including IGF1 and low SDF-1α, with options for angiogenic factors such as VEGF. Mineralization is described as occurring around integrated ceramic particles, consistent with the osteogenic phenotype of the differentiated ASCs.
A method is provided for producing the scaffold-free three-dimensional biomaterial by isolating autologous ASCs from a human subject, proliferating the isolated ASCs in vitro, and differentiating the proliferated ASCs in vitro into an osteogenic cell phenotype. HA/B-TCP particles are added homogenously to the surface of the osteogenic differentiated ASCs, followed by culturing the osteogenic differentiated ASCs with the particles to produce the scaffold-free three-dimensional biomaterial. The integrated ECM and ceramic particles are maintained in the resulting multi-dimensional scaffold-free structure.
Claims Coverage
The independent claim covers the production of a scaffold-free three-dimensional biomaterial defined by autologous ASC osteogenic differentiation, homogenously added HA/B-TCP particles, integration into ASC-secreted ECM, and a minimum OPG secretion threshold. Dependent claims refine additional biological or biochemical characteristics, including quantitative secretion or content constraints and mineralization around HA/B-TCP particles.
Scaffold-free three-dimensional biomaterial produced by autologous ASC osteogenic differentiation with integrated HA/B-TCP particles
A scaffold-free three-dimensional biomaterial comprising autologous adipose stem cells (ASCs) isolated from a human subject, proliferated in vitro, differentiated into an osteogenic cell phenotype in vitro, and then cultured with homogenously added particles comprising a mixture of hydroxyapatite (HA) and beta-tricalciumphosphate (B-TCP), thereby producing a scaffold-free three-dimensional biomaterial where the ASCs and the particles are integrated into an extracellular matrix (ECM) secreted by the ASCs.
OPG secretion threshold per biomaterial mass
The biomaterial secretes at least about 5 ng of osteoprotegerin (OPG) per g of biomaterial.
Mineralization surrounding HA/B-TCP particles
The three-dimensional biomaterial is characterized by mineralization surrounding HA and B-TCP particles.
Overall, the claim set centers on a scaffold-free three-dimensional biomaterial made from autologous ASCs that are osteogenic differentiated and combined with homogenously added HA/B-TCP particles integrated into ASC-secreted ECM, with a defined OPG secretion level. The dependent refinements add quantitative constraints and a mineralization pattern around the ceramic particles.
Stated Advantages
Provides a scaffold-free three-dimensional biomaterial that is essentially free of any exogenous extracellular matrix while containing ECM secreted by the ASCs.
Provides osteogenic mineralization characterized as occurring around integrated HA/B-TCP particles.
Provides osteogenic and osteoinductive biological function as stated by 'osteoinductive'.
Provides osteoprotegerin (OPG) secretion at a specified minimum per mass of biomaterial.
Documented Applications
Therapeutic use for bone/cartilage defects, notably congenital pseudarthrosis of the tibia.
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