Tissue-derived tissuegenic implants, and methods of fabricating and using same

Abstract

The disclosure provides implants containing a plurality of particles containing at least one population of viable cells adherent to and resident in soft tissue matrix or at least one viable population of cells caused to be in contact with the soft tissue matrix; methods of fabricating the implants; and use of the implants in tissue repair.

What is claimed is: 
     
         1 . A method for treating a tissue defect at a defect site in a subject in need thereof, the method comprising the steps of:
 (a) providing a tissue-derived implant which comprises: (i) at least one tissue-derived growth conductive matrix of the donor from which measurable immunologically reactive hematopoietic cells have been removed; and (ii) at least one viable population of nonexpanded tissuegenic cells endogenous to the growth conductive matrix of the donor that remains adherent to and resident in an endogenous milieu of the growth conductive matrix; with the proviso that, before implantation, the implant is not reconstituted with cells exogenous to the tissue-derived growth conductive matrix of the donor; and   (b) implanting the tissue-derived implant at the defect site.   
     
     
         2 . The method according to  claim 1 , further comprising (c) filling at least a portion of the tissue defect with at least a portion of the implant. 
     
     
         3 . The method according to  claim 1 , wherein the tissue defect comprises one or more of: a fracture, diseased tissue, atrophied tissue, a cavity, a space, a pocket, a surgical site, and a void volume. 
     
     
         4 . The method according to  claim 1 , wherein the implant further comprises (iii) at least one growth-inductive component. 
     
     
         5 . The method according to  claim 4 , wherein the growth-inductive component is tissue-derived. 
     
     
         6 . The method according to  claim 4 , wherein the (i) at least one tissue-derived growth inductive matrix and the (iii) at least one growth-inductive component of the implant are provided separately, the method further comprising the step of: combining the (i) at least one tissue-derived growth inductive component and the (iii) at least one growth-inductive component together prior to the step of (b) implanting the implant at the defect site. 
     
     
         7 . The method according to  claim 1 , wherein the (i) at least one tissue-derived growth conductive matrix comprising a plurality of pieces of growth conductive matrix. 
     
     
         8 . The method according to  claim 1 , wherein the at least one population of tissuegenic cells is present in the growth conductive matrix at a relative frequency substantially similar to the relative frequency of the tissuegenic cells found in vivo. 
     
     
         9 . The method according to  claim 1 , where in the tissue defect comprises a bony defect. 
     
     
         10 . The method according to  claim 9 , wherein the bony defect comprises one or more of: a bone fracture, diseased bone tissue, atrophied bone tissue, a cavity in bone tissue, a space in bone tissue, a pocket in bone tissue, a surgical site comprising bone tissue, and a void volume in bone tissue. 
     
     
         11 . The method according to  claim 10 , wherein the surgical site comprising bone tissue comprises a spinal arthrodesis surgical site. 
     
     
         12 . The method according to  claim 9 , further comprising (c) filling at least a portion of the bony defect with at least a portion of the implant. 
     
     
         13 . The method of  claim 1 , wherein the recipient of the tissue-derived implant is allogeneic to a donor of the implant or tissue samples from which the implant was derived. 
     
     
         14 . A method for treating a bone defect at a defect site in a subject in need thereof, the method comprising the steps of:
 (a) providing a composition comprising: a cryopreserved mixture prepared without exogenous enzymes and including at least one osteoconductive matrix which includes cancellous bone particles; at least one viable population of endogenous osteogenic cells adherent to and resident in an endogenous milieu of at least some of the cancellous bone particles; and a demineralized bone matrix; and   (b) implanting the composition at the defect site.   
     
     
         15 . The method according to  claim 14 , further comprising (c) filling at least a portion of the bony defect with at least a portion of the composition. 
     
     
         16 . The method according to  claim 14 , wherein the bony defect comprises one or more of: a bone fracture, diseased bone tissue, atrophied bone tissue, a cavity in bone tissue, a space in bone tissue, a pocket in bone tissue, and a void volume in bone tissue. 
     
     
         17 . A method for treating a bony defect at a defect site in a subject in need thereof, the method comprising the steps of:
 (a) providing a composition consisting essentially of: cancellous bone particles, wherein the cancellous bone particles have osteoconductive properties; wherein the cancellous bone particles have viable endogenous osteogenic cells; and demineralized cortical bone fibers, wherein the demineralized cortical bone fibers have osteoinductive properties; wherein a sufficient amount of the demineralized cortical bone fibers results in the composition having improved cohesion compared to a composition consisting of less than a sufficient amount of demineralized cortical bone fibers and no other carrier; and   (b) implanting the composition at the defect site.   
     
     
         18 . The method according to  claim 17 , further comprising (c) filling at least a portion of the bony defect with at least a portion of the composition. 
     
     
         19 . The method according to  claim 17 , wherein the bony defect comprises one or more of: a bone fracture, diseased bone tissue, atrophied bone tissue, a cavity in bone tissue, a space in bone tissue, a pocket in bone tissue, a surgical site comprising bone tissue, and a void volume in bone tissue. 
     
     
         20 . The method according to  claim 19 , wherein the surgical site comprising bone tissue comprises a spinal arthrodesis surgical site.