Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof
Inventors
Smith, Robert Lane • Tarrant, Laurence J. B. • Kusanagi, Akihiko • CLAESSON, HANS P. I.
Assignees
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Publication Number
US-10900017-B2
Publication Date
2021-01-26
Expiration Date
Abstract
A cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof. The matrix suitable for preparation of cellular or acellular implants for growth and de novo formation of an articular hyaline-like cartilage. A gel-matrix composite system comprising collagen-based matrix having a narrowly defined porosity capable of inducing hyaline-like cartilage production from chondrocytes in vivo and in vitro.
Core Innovation
The described invention relates to a collagen-based cell-support matrix and implant for articular cartilage repair. The matrix comprises a porous collagen body having a top surface and an opposed basal surface, with a plurality of pores of substantially uniform pore size and orientation extending from the top surface to the basal surface, and the porosity is non-randomly organized.
A type I collagen porous body is used, and a sol-gel is disposed within the pores, where the sol-gel gels at body temperature. Chondrocytes are suspended within the sol-gel and are supported by the vertically oriented pores that extend through the collagen matrix. The pore structure enables sterically enhanced induction of hyaline or hyaline-like cartilage formation, including deposition of extracellular matrix components such as type II collagen and sulfated glycosaminoglycans as part of de novo cartilage formation.
The disclosure includes controlling pore size and pore density in a collagen-based system to influence biochemical outcomes and viability. Comparative analyses using assays for sulfated glycosaminoglycans and DNA content describe improved cartilage-specific extracellular matrix production with smaller pores relative to larger pores, alongside high cell viability.
Claims Coverage
Two independent claims are identified, and they share inventive features centered on a porous collagen implant with vertically oriented, substantially uniform pores, combined with a sol-gel that gels at body temperature and chondrocytes supported within the pores. The claim set further constrains pore size distribution and composition in the cartilage implant context.
Porous collagen body with vertically oriented substantially uniform pores
A porous body comprising collagen, with a top surface and an opposed basal surface, and a plurality of pores of substantially uniform pore size and orientation extending from the top surface to the basal surface.
Type I collagen cartilage implant with uniformly sized pores filled with a body-temperature gelling sol-gel containing chondrocytes
A cartilage implant comprising a porous body comprising type I collagen disposed between a top surface and an opposed basal surface, wherein the porous body has a plurality of pores of substantially uniform pore size and orientation extending from the top surface to the basal surface; about 95% of the pores have a diameter of about 200 plus or minus 100 microns; a sol-gel that gels at a body temperature disposed within the pores; and a plurality of chondrocytes suspended within the sol-gel.
Overall, the independent claims require a porous collagen body with substantially uniform pore size and defined pore orientation extending through the thickness, and the cartilage implant further specifies a type I collagen body together with a body-temperature gelling sol-gel disposed within the pores and chondrocytes suspended in the sol-gel, including a quantitative pore diameter distribution.
Stated Advantages
Sterically enhanced induction of hyaline or hyaline-like cartilage formation.
Improved cartilage-specific extracellular matrix production associated with smaller pores versus larger pores, as supported by sulfated glycosaminoglycans and DNA content comparisons.
High cell viability.
Documented Applications
Articular cartilage repair using a collagen-based cell-support matrix/implant supporting chondrocytes for in vitro and in vivo cartilage formation.
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