Acellular matrix implants for treatment of articular cartilage, bone or osteochondral defects and injuries and a method for use thereof

Abstract

An acellular matrix implant for treatment of defects and injuries of articular cartilage, bone or osteochondral bone and a method for treatment of injured, damaged, diseased or aged articular cartilage or bone, using the acellular matrix implant implanted into a joint cartilage lesion in situ and a bone-inducing composition implanted into an osteochondral or bone defect. A method for repair and restoration of the injured, damaged, diseased or aged cartilage or bone into its full functionality by implanting the acellular matrix implant between two layers of biologically acceptable sealants and/or the bone-inducing composition into the osteochondral bone or skeletal bone defect. A method for fabrication of the acellular matrix implant of the invention. A method for preparation of bone-inducing composition.

1 . A method for treatment of injury of an articular cartilage and for repair and restoration of damaged, injured, diseased or aged cartilage to a functional hyaline cartilage, said method comprising steps: 
 a) preparing an acellular matrix implant; and    b) implanting said implant into an articular cartilage lesion.    
   
   
       2 . The method of  claim 1  wherein said acellular matrix implant is a sponge, porous or honeycomb scaffold, sol-gel, gel, a polymer of an aromatic organic acid or thermo-reversible hydrogel.  
   
   
       3 . The method of  claim 2  additionally comprising a step of depositing a layer of a biologically acceptable top sealant over said implant implanted into said lesion.  
   
   
       4 . The method of  claim 3  further comprising a step of depositing a layer of a biologically acceptable bottom sealant over a bottom of said lesion.  
   
   
       5 . The method of  claim 4  wherein said top and said bottom sealants are the same or different.  
   
   
       6 . The method of  claim 5  wherein a combination of said implant and said top sealant results in formation and growth of a superficial cartilage layer sealing the cartilage lesion in situ.  
   
   
       7 . The method of  claim 6  additionally comprising a step of debridement of the articular cartilage lesion and during the debridement, preparing the lesion for implantation of the acellular matrix implant by depositing the bottom sealant at the bottom of the lesion thereby insulating said cavity from the surrounding tissue.  
   
   
       8 . The method of  claim 7  further comprising a step of optionally introducing enzymes, hormones, growth factors, proteins, peptides and mediators, or drugs promoting an endogenous production of these factors or mediators, into said sealed cavity or generating conditions for their transport or transfer through the bottom sealant.  
   
   
       9 . The method of  claim 7  further comprising a step of subjecting an individual undergoing a surgery for repair of said lesion to a normal physical activity thereby naturally providing an intermittent hydrostatic pressure which promotes a formation of the functional hyaline cartilage and its integration into a surrounding native intact cartilage.  
   
   
       10 . The method of  claim 1  wherein the acellular matrix implant is prepared from a material selected from the group consisting of a Type I collagen, a Type II collagen, a Type IV collagen, a cell-contracted collagen containing proteoglycan, a cell-contracted collagen containing glycosaminoglycan, a cell-contracted collagen containing glycoprotein, a polymer of an aromatic organic acid, gelatin, agarose, hyaluronin, fibronectin, laminin, a bioactive peptide growth factor, a cytokine, elastin, fibrin, a polymer of an aromatic organic acid or a copolymer thereof, a synthetic polymeric fiber made of polylactic acid, a synthetic polymeric fiber made of polyglycolic acid, polycaprolactones, a polyamino acid, a polypeptide gel, a polymeric thermo-reversible gelling hydrogel (TRGH), a copolymer thereof and a combination thereof.  
   
   
       11 . The method of  claim 10  wherein said material for preparation of the acellular matrix implant is the thermo-reversible gelation hydrogel.  
   
   
       12 . The method of  claim 11  suitable for treatment of the articular cartilage injury comprising steps: 
 a) preparation of the acellular matrix implant;    b) debridement of said lesion during the surgery;    c) preparation of the cartilage lesion for implantation of said implant, including a step of depositing the bottom sealant at the bottom of the cartilage lesion for sealing of said lesion and protecting the implant from migration of blood-borne agents;    d) implanting the implant into the lesion;    e) depositing the top sealant over the acellular matrix implant; and    f) following the surgery, subjecting an individual undergoing a surgery for repair of said lesion to a normal physical activity thereby naturally providing an intermittent hydrostatic pressure.    
   
   
       13 . The method of  claim 12  wherein said acellular matrix implant is a biodegradable collagenous sponge, honeycomb sponge, collagenous porous scaffold, a polymer of an aromatic organic acid or thermo-reversible gelation hydrogel (TRGH) matrix.  
   
   
       14 . The method of  claim 13  wherein said matrix additionally comprises matrix remodeling enzymes, matrix metalloproteinases, aggrecanases and cathepsins.  
   
   
       15 . The method of  claim 14  wherein the acellular matrix implant is the thermo-reversible gelation hydrogel (TRGH) deposited into a lesion cavity formed above the bottom sealant layer, or into the cavity between the top and bottom sealant, said TRGH deposited into said cavity either incorporated into a collagenous sponge or scaffold or as a sol at temperatures between about 5 to about 30° C., wherein within said cavity and at the body temperature said TRGH converts from the fluidic sol into a solid gel.  
   
   
       16 . A method for treatment of osteochondral defects, said method comprising steps: 
 a) preparing a bone-inducing composition or a carrier comprising said composition, said composition comprising one or several bone-inducing agents, for implantation into a bone lesion;    b) preparing an acellular matrix implant for implantation into a cartilage lesion as a collagenous sponge, collagenous porous scaffold, a polymer of an aromatic organic acid or thermo-reversible gelation hydrogel (TRGH) matrix support wherein said sponge, scaffold, polymer or TRGH are biodegradable, will disintegrate with time, be removed and replaced with a hyaline cartilage;    c) introducing said bone-inducing composition or a carrier comprising said composition into a bone lesion;    d) covering said bone-inducing composition or the carrier comprising said composition with a bottom sealant;    e) implanting said acellular matrix implant into said cartilage lesion over the bottom sealant; and    f) introducing a layer of a top sealant over said implant wherein said top and bottom sealants may or may not be the same.    
   
   
       17 . The method of  claim 16  wherein said inducing agent is selected from the group consisting of a demineralized bone powder, hydroxyapatite, organoapatite, calcium phosphate, titanium oxide, poly-L-lactic acid, polyglycolic acid, a copolymer thereof and a bone morphogenic protein.  
   
   
       18 . The method of  claim 17  wherein said bone-inducing agent is hydroxyapatite.  
   
   
       19 . The method of  claim 17  wherein said bone-inducing agent is the demineralized bone powder.  
   
   
       20 . The method of  claim 19  wherein said demineralized bone powder is dissolved in collagen.  
   
   
       21 . The method of claims  16  wherein said carrier comprising the bone-inducing agent is a polymer of an aromatic organic acid.  
   
   
       22 . A method for treatment of bone defects and fractures, said method comprising steps: 
 a) preparing a bone-inducing composition or an implant carrier comprising said composition, said composition comprising one or several bone-inducing agents for implantation into a bone lesion;    b) introducing said bone-inducing composition or said carrier comprising said composition into the bone lesion;    c) covering said bone-inducing composition or said carrier comprising said composition with a layer of a sealant.    
   
   
       23 . The method of  claim 22  wherein said bone-inducing agent is selected from the group consisting of a demineralized bone powder, hydroxyapatite, organoapatite, calcium phosphate, titanium oxide, poly-L-lactic acid, polyglycolic acid, a copolymer thereof and a bone morphogenic protein.  
   
   
       24 . The method of  claim 23  wherein said bone-inducing agent is the demineralized bone powder.  
   
   
       25 . The method of  claim 24  wherein said demineralized bone powder is mixed with collagen into a stable paste.  
   
   
       26 . The method of claims  23  wherein said carrier comprising said bone-inducing agent is a polymer of an organic aromatic acid.  
   
   
       27 . The method of  claim 23  wherein said bone-inducing agent is the hydroxyapatite.  
   
   
       28 . The method of  claim 23  wherein said bone-inducing composition is the bone morphogenic protein.  
   
   
       29 . The method of claims  23  wherein said bone-inducing agent is titanium oxide.  
   
   
       30 . An acellular matrix implant for implantation into a cartilage lesion, said implant comprising a collagenous, sol-gel, polymer of an aromatic organic acid or thermo-reversible hydrogel material fabricated as a sponge or porous or honeycomb scaffold.  
   
   
       31 . The implant of  claim 30  wherein said collagenous material further comprises a compound selected from the group consisting of a mediator, growth factor, enzyme, protein, peptide and a drug enhancing endogenous production of the mediator, factor, enzyme, protein or peptide.  
   
   
       32 . A sealant for sealing of a top or bottom cartilage or bone lesion wherein said sealant is biologically compatible with cartilage or bone tissue, non-toxic and biodegradable.  
   
   
       33 . The sealant of  claim 32  wherein the sealant is a rapidly gelling polymer from a flowable liquid or paste to a load-bearing gel within 30 seconds to 5 minutes.  
   
   
       34 . The sealant of  claim 33  possessing a minimal peel strengths of at least about 3N/m to about to 30 N/m, a cohesive strength, measured as tensile strength in the range of from about 0.2 MPa to about 1.0 MPa or has a bond strength of at least 0.5 N/cm 2  to about 6 N/cm 2 .  
   
   
       35 . The sealant of  claim 34  wherein said sealant is a gel having a cohesive strength dependent on the number of inter-chain linkages.  
   
   
       36 . The sealant of  claim 35  which has adhesive or peel strengths at least 10 N/m and tensile strength at least 0.3 MPa.  
   
   
       37 . The sealant of  claim 35  which has adhesive or peel strengths of 100 N/cm and tensile strength in the range from 0.8 to 1.0 MPA.