Tissue implant

Abstract

A biochemical implant is described which comprises at least two matrix components. The first matrix component is composed of collagen with a porous macrostructure with the ability to withstand tensile or shear forces. The second matrix component is a hydrated alginate gel which substantially fills the porous macrostructure of the first component and exerts a swelling pressure. The implant additionally comprises a population of cells comprising chondrocytes, fibrochondrocytes, fibroblasts or osteoblasts, or precursors thereof.

1 . A biomechanical implant comprising at least two matrix components, the first matrix component having a porous macrostructure with the ability to withstand tensile or shear forces, the second matrix component being a hydrated gel which substantially fills the porous macrostructure of the first component and exerts a swelling pressure, the implant additionally comprising a population of animal cells having a differentiated biomechanical phenotype or having an undifferentiated phenotype with the potential to differentiate into such cells.  
     
     
         2 . A biomechanical implant as claimed in    claim 1   , in which the implant is a full or partial replacement for a tissue where there is a mechanical interaction in both the loaded and unloaded states sufficient to set up an equilibrium between major matrix components.  
     
     
         3 . A biomechanical implant as claimed in    claim 2   , in which the tissue comprises cartilage, temperomandibular joint meniscus, knee meniscus or an intervertebral disc.  
     
     
         4 . A biomechanical implant as claimed in any one of    claims 1    to    3   , in which the first matrix component is composed of a biodegradable or bioresorbable polymer.  
     
     
         5 . A biomechanical implant as claimed in    claim 4   , in which the biodegradable or bioresorbable polymer comprises collagen, gelatin, poly-L-lactic acid, poly-glycolic acid, polycaprolactone, polyhydroxybutarate, polyanhydrides or a copolymer thereof  
     
     
         6 . A biomechanical implant as claimed in    claim 4    or    claim 5   , in which the biodegradable or bioresorbable polymer is modified by crosslinking agents.  
     
     
         7 . A biomechanical implant as claimed in any one of    claims 4    to    6   , in which the first matrix component further comprises a coating of hydroxyapatite, fibronectin, collagen, vitronectin, hyaluronan, proteoglycans, glycosaminoglycans or RGD (Arg-Gly-Asp).  
     
     
         8 . A biomechanical implant as claimed in any one of    claims 4    to    7   , in which the coating is restricted to specified portions of the implant.  
     
     
         9 . A biomechanical implant as claimed in any one of    claims 4    to    8   , in which the first matrix component has a groove or microporosities in the range 0.1-50 μm, suitably 1-25 μm, preferably 3-10 μm.  
     
     
         10 . A biomechanical implant as claimed in any one of    claims 4    to    9   , in which the polymeric components forming the first matrix component have an average pore size ranging from 10-1000 μm, suitably 30-250 μm, preferably 50-150 μm with a total porosity ranging from 50-98%, suitably 60-95%, preferably 70-90%.  
     
     
         11 . A biomechanical implant as claimed in any one of    claims 1    to    10    which is in the form of woven or non-woven fibres, sponges, foams, or a series of plates or sheets joined by interconnecting strands, fibres or adjoining plates.  
     
     
         12 . A biomechanical implant as claimed in any one of    claims 1    to    11   , in which the hydrated gel which forms the second matrix component is a hydrated polymeric gel.  
     
     
         13 . A biomechanical implant as claimed in any one of    claims 1    to    12   , in which the hydrated polymeric gel is biodegradable or bioresorbable.  
     
     
         14 . A biomechanical implant as claimed in    claim 12    or    claim 13   , in which the hydrated polymeric gel comprises alginate, agarose, carrageenans, glycosaminoglycans, proteoglycans, polyethylene oxide or collagen monomers.  
     
     
         15 . A biomechanical implant as claimed in any one of    claims 12    to    14   , in which the hydrated gel is heterogeneous in nature.  
     
     
         16 . A biomechanical implant as claimed in any one of    claims 12    to    15   , in which the hydrated gel is cross-linked.  
     
     
         17 . A biomechanical implant as claimed in any one of    claims 12    to    16   , in which the hydrated gel further comprises collagen, hydroxyapatite, growth factors, cytokines, cell attachment factors, chemotactic factors, angiogenic factors or enzymes.  
     
     
         18 . A biomechanical implant as claimed in any one of    claims 1    to    17   , in which the animal cells in the implant are autologous, allogeneic or xenogeneic with respect to the host.  
     
     
         19 . A biomechanical implant as claimed in    claim 18   , in which the cells comprise chondrocytes, fibrochondrocytes, fibroblasts or osteoblasts, or sub-populations thereof, or precursors thereof.  
     
     
         20 . A biomechanical implant as claimed in    claim 18    or    claim 19   , in which the cells are derived from a tissue biopsy.  
     
     
         21 . A method of repairing damaged connective tissue, in which the method comprises the step of wholly or partially replacing the damaged tissue with a biomechanical implant as defined in any of    claims 1    to    20   .  
     
     
         22 . The use of at least two matrix components, the first matrix component having a porous macrostructure with the ability to withstand tensile or shear forces, the second matrix component being a hydrated gel which substantially fills the porous macrostructure of the first component and has the ability to withstand compressive loading, and a population of animal cells having a differentiated biomechanical phenotype or having an undifferentiated phenotype with the potential to differentiate into such cells, in the preparation of a biomechanical implant for repair of damaged connective tissue.  
     
     
         23 . The use as claimed in    claim 22   , in which the tissue to be repaired is cartilage, temperomandibular joint menisci, knee menisci or intervertebral discs.  
     
     
         24 . A biomechanical implant comprising at least two matrix components the first matrix component having a porous macrostructure with the ability to withstand tensile or shear forces, the second matrix component being a hydrated gel which substantially fills the porous macrostructure of the first component and has the ability to withstand compressive loading, the implant additionally comprising a population of animal cells having a differentiated biomechanical phenotype or having an undifferentiated phenotype with the potential to differentiate into such cells, as a combined preparation for simultaneous, separate or sequential use in the preparation of a biomechanical implant for repair of damaged connective tissue.  
     
     
         25 . A method for the manufacture of a biomechanical implant as defined in any one of    claims 1    to    20   , in which the method comprises the steps of: 
 (a) infiltrating a solution of the uncrosslinked precursors of the hydrated gel into the first matrix component,  
 (b) crosslinking the gel in situ to form the second matrix component,  
 (c) incorporating the cells into the matrix, and  
 (d) applying a mechanical loading.  
 
     
     
         26 . A method as claimed in    claim 25   , in which the uncrosslinked precursors of the hydrated gel are infiltrated into the first matrix component by diffusion, vacuum infiltration or centrifugation.  
     
     
         27 . A method as claimed in    claim 25    or    claim 26   , in which the cells are incorporated into the matrix (i) by direct attachment to the first matrix component, (ii) by addition of the cells to the solution of the second matrix component prior to infiltration into the first matrix component, or (iii) by attachment of the cells to the first matrix component and immobilisation of cells within the second matrix component.