Solid forms for tissue repair

Abstract

This invention provides aragonite- and calcite-based scaffolds for the repair, regeneration, enhancement of formation or a combination thereof of cartilage and/or bone, which scaffolds comprise at least two phases, wherein each phase differs in terms of its chemical content, or structure, kits comprising the same, processes for producing solid aragonite or calcite scaffolds and methods of use thereof.

1 - 104 . (canceled) 
     
     
         105 . A scaffold for tissue repair, said scaffold consisting essentially of two phases wherein:
 a first phase of said two phases comprises solid coral and a biocompatible polymer and said first phase further comprises a series of hollows along a longitudinal axis in said first phase; and   a second phase of said two phases comprises a solid coral.   
     
     
         106 . The scaffold of  claim 105 , wherein said biocompatible polymer is a glycosaminoglycan, collagen, elastin, silk, chitosan, alginate, or a combination thereof. 
     
     
         107 . The scaffold of  claim 106 , wherein said glycosaminoglycan is hyaluronic acid or sodium hyaluronate. 
     
     
         108 . The scaffold of  claim 105 , wherein said biocompatible polymer comprises a synthetic biodegradable polymer, which comprises alpha-hydroxy acids. 
     
     
         109 . The scaffold of  claim 105 , wherein said scaffold further comprises a cytokine, a chelator, a cell population, an anti-inflammatory compound, an anti-infective compound, a growth factor, an antibiotic, a pro-angiogenic factor, a therapeutic compound, or any combination thereof. 
     
     
         110 . The scaffold of  claim 109 , wherein said cell population comprises mesenchymal stem cells, osteoblasts, osteocytes, osteoclasts, chondroblasts, chondrocytes, fibroblasts, or a combination thereof, or other cells involved in cartilage or bone repair. 
     
     
         111 . The scaffold of  claim 109 , wherein said growth factor is epidermal growth factor (EGF), transforming growth factor-beta (TGF-β), human endothelial cell growth factor (ECGF), granulocyte macrophage colony stimulating factor (GM-CSF), bone morphogenetic protein (BMP), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), cartilage derived morphogenetic protein (CDMP), platelet derived growth factor (PDGF), or a combination thereof. 
     
     
         112 . The scaffold of  claim 105 , wherein said scaffold approximates the form of a cylinder, cone, screw, rectangular bar, plate, disc, pyramid, granule, ball or cube. 
     
     
         113 . The scaffold of  claim 105 , wherein the scaffold assumes a shape to approximate a meniscus for a knee or elbow; a joint; an articular surface of a bone, a portion of a rib cage, a hip, a pelvis, an ear, a nose, a ligament, a bronchial tube or an intervertebral disc. 
     
     
         114 . The scaffold of  claim 105 , wherein said scaffold is cylindrical in shape and has a diameter of about 5-40 mm, and a height of about 5-25 mm. 
     
     
         115 . The scaffold of  claim 105 , wherein said biocompatible polymer is in the form of a polymer coating, forming a polymer layer associated with a portion of said scaffold. 
     
     
         116 . The scaffold of  claim 115 , wherein said polymer coating is present at a terminus of said scaffold and said coating has a thickness of between about 0.1-10 mm. 
     
     
         117 . The scaffold of  claim 115 , wherein said polymer is in the form of a hydrogel. 
     
     
         118 . A method of inducing or enhancing repair, regeneration or enhancement of formation of cartilage, bone or a combination thereof, said method comprising implanting in a subject, a scaffold of  claim 105  within a site in need of repair, regeneration or enhancement of formation of cartilage, bone or a combination thereof in said subject. 
     
     
         119 . The method of  claim 118 , wherein said cartilage defect or disorder comprises a full or partial thickness articular cartilage defect; osteochondral defect; osteoarthritis; osteochondritis dissecans; a joint defect; or a defect resulting from trauma, sports, or repetitive stress. 
     
     
         120 . The method of  claim 118 , wherein said scaffold is positioned such that said at least a second porous phase is implanted within or proximally to cartilage tissue and said at least a first porous phase is implanted within or proximally to bone tissue. 
     
     
         121 . A kit for repair of cartilage or bone comprising the scaffold of  claim 105 , and directions for utilizing said scaffold in tissue repair. 
     
     
         122 . A process for the purification of a coralline-based scaffolding, said process comprising the steps of:
 contacting solid aragonite of a desired size and shape with a solution comprising an oxidizing agent; and   washing and drying said solid aragonite   
       whereby one or each of said steps is conducted under applied negative pressure. 
     
     
         123 . The process of  claim 122 , wherein said process comprises conducting said contacting under mildly acidic conditions and said solution comprises sodium hypochlorite, wherein said process further comprises subjecting the solid aragonite to a temperature of at least 275° C. under applied negative pressure, and wherein said applied negative pressure ranges from 0.2 to 0.00001 Bar. 
     
     
         124 . The kit of  claim 121 , which further comprises a tool or tools for optimal insertion of said scaffold. 
     
     
         125 . The kit of  claim 121 , which further comprises a series of scaffolds of different sizes or shapes. 
     
     
         126 . The kit of  claim 121 , which further comprises a tool or tools for optimal insertion of said scaffold, and a series of scaffolds of different sizes or shapes. 
     
     
         127 . The scaffold of  claim 108 , wherein said alpha-hydroxy acids comprise poly-lactic acid, polyglycolic acid, enantioners thereof, co-polymers thereof, polyorthoesters, or combinations thereof. 
     
     
         128 . The scaffold of  claim 106 , wherein said biocompatible polymer is a glycosaminoglycan. 
     
     
         129 . The scaffold of  claim 128 , wherein said glycosaminoglycan is hyaluronic acid or sodium hyaluronate. 
     
     
         130 . A method of inducing or enhancing repair, regeneration or enhancement of formation of cartilage, bone or a combination thereof, said method comprising implanting in a subject, a scaffold within a site in need of repair, regeneration or enhancement of formation of cartilage, bone or a combination thereof in said subject, said scaffold consisting essentially of two phases:
 a first phase of said two phases comprising solid coral and a series of hollows along a longitudinal axis in said first phase; and   a second phase of said two phases comprising a solid coral,   
       wherein a biocompatible polymer is applied to said first phase. 
     
     
         131 . The method of  claim 130 , wherein said cartilage defect or disorder comprises a full or partial thickness articular cartilage defect; osteochondral defect; osteoarthritis; osteochondritis dissecans; a joint defect; or a defect resulting from trauma, sports, or repetitive stress. 
     
     
         132 . The method of  claim 130 , wherein said scaffold is positioned such that said at least a second porous phase is implanted within or proximally to cartilage tissue and said at least a first porous phase is implanted within or proximally to bone tissue.