Medical/Surgical Implant

Abstract

The present invention relates to the field of implants. In particular, the present invention relates to an implant for tissue reconstruction which comprises a scaffold structure that includes a void system for the generation of prevascularized connective tissue with void spaces for cell and/or tissue transplantation. Moreover, the present invention relates to a method of manufacturing such an implant, to the internal architecture of such an implant, to a removal tool for mechanical removal of space-occupying structures from such an implant, to a kit comprising such an implant and such a removal tool, to a removal device for the removal of superparamagnetic or ferromagnetic space-occupying structures from such an implant, as well as to a guiding device for providing feedback to a surgeon during the procedure of introducing transplantation cells into the void spaces generated upon removal of space-occupying structures from such an implant.

1 . A method for tissue reconstruction in the body of a patient, comprising the following steps in order:
 a) implanting an implant comprising a three-dimensional scaffold structure made of biodegradable material into said body of said patient at the site of intended tissue reconstruction;   b) after a time period sufficient to allow connective tissue and/or host vasculature to penetrate into said three-dimensional scaffold structure introducing transplantation cells to the site of intended tissue reconstruction.   
     
     
         2 . The method of  claim 1 , wherein said time period sufficient to allow connective tissue and/or host vasculature to penetrate into said three-dimensional scaffold structure is in the range of 4-12 weeks. 
     
     
         3 . The method of  claim 1 , wherein said time period sufficient to allow connective tissue and/or host vasculature to penetrate into said three-dimensional scaffold structure is in the range of 6-8 weeks. 
     
     
         4 . The method of  claim 1 , wherein said transplantation cells are a mixture of cells obtained by lipoaspiration. 
     
     
         5 . The method of  claim 4 , further comprising a step of obtaining a mixture of cells by lipoaspiration, wherein the method comprises the additional steps of making an incision at the site where the fat is to be obtained, and aspirating fat using a blunt needle with multiple perforations and an aspirator. 
     
     
         6 . The method of  claim 4 , further comprising a step of filtering the fat to separate one or more of blood, oil and local anesthetic from the fat cells. 
     
     
         7 . The method of  claim 1 , wherein said transplantation cells are one of stem cells, progenitor cells and fully differentiated cells. 
     
     
         8 . The method of  claim 1 , wherein said transplantation cells are individual cells which are not physically linked to each other. 
     
     
         9 . The method of  claim 1 , wherein said presentation cells are formed by groups of cells that are physically linked to each other. 
     
     
         10 . The method of  claim 1 , wherein said transplantation cells comprise cells selected from the group consisting of epidermic cells, pancreatic parenchymal cells, pancreatic duct cells, hepatic cells, blood cells, cardiac muscle cells, skeletal muscle cells, osteocytes, myocytes, neurons, vascular endothelial cells, pigment cells, smooth muscle cells, adipocytes, bone cells, chondrocytes, or combinations thereof. 
     
     
         11 . The method of  claim 1 , wherein said transplantation cells are cardiomyocytes, cells derived from pancreas, or chondrocytes. 
     
     
         12 . The method of  claim 1 , wherein said transplantation cells are selected from a group consisting of thymocytes, megakaryoblast, promegakaryocytes, lymphoblast, bone marrow precursor cells, normoblast, angioblasts, osteoblasts, skeletal myoblasts, myeloid progenitor cells, satellite cells found in muscles, and transit amplifying neural progenitors, or combinations thereof. 
     
     
         13 . The method of  claim 1 , wherein said transplantation cells are selected from the group consisting of adipose tissue-derived precursor cells (APCs), bone marrow-derived precursor cells, periosteum-derived progenitor cells and Umbilical-cord-derived precursor cells, or combinations thereof. 
     
     
         14 . The method of  claim 1 , wherein said transportation cells are of autologous origin with respect to the patient. 
     
     
         15 . The method of  claim 1 , wherein said transplantation cells are syngeneic. 
     
     
         16 . The method according to  claim 1 , wherein said biodegradable material is selected from the group consisting of polycaprolactone, poly(1,3-trimethylene carbonate), polylactide, polyglycolide, poly(ester amide), poly(ethylene glycol)/poly(butylene terephthalate), poly(glycerol sebacate), poly(1,8-octanediol-co-citric acid), poly(1,10-decanediol-co-D,L-lactic acid), poly(diol citrate), poly(glycolide-co-caprolactone), poly(1,3-trimethylene carbonate-co-lactide), poly(1,3-trimethylene carbonate-co-caprolactone) and a copolymer of at least two of these materials, wherein, more preferably said biodegradable material is either polycaprolactone or a copolymer of polycaprolactone and either poly-trimethylene carbonate or polylactide. 
     
     
         17 . The method according to  claim 1 , wherein said implant is a soft tissue implant. 
     
     
         18 . The method according to  claim 1 , wherein said implant is selected from the group consisting of a breast implant, an implant of the salivary gland, a pancreas implant, a bone implant, an implant to reconstruct an anterior cruciate ligament tear, a craniofacial reconstruction implant, a maxillofacial reconstruction implant, a complex jaw surgery implant, a post tumor-resection reconstruction implant, an implant for tissue reconstruction after removal of a melanoma, an implant for tissue reconstruction after removal of a head and neck cancer, an ear implant, a nose implant, a chest wall reconstruction implant, an orthopedic surgery implant, a cartilage reconstruction implant and a delayed burn reconstruction implant, wherein, more preferably, said implant is a breast implant. 
     
     
         19 . The method according to  claim 1 , wherein said three-dimensional scaffold structure comprises a stack of multiple interconnected layers, each layer being composed of a plurality of, preferably parallel, bars, wherein
 a) said bars have a zigzag structure or a wiggled structure; or   b) the bars of every n-th layer within said stack have a zigzag structure or a wiggled structure whereas the bars of all other layers are straight bars,
 wherein n is an integer in the range of from 2 to 5, preferably 2 or 3, more preferably 2; or 
   c) each layer comprises bars that have a zigzag structure or a wiggled structure, wherein, preferably, at least 1/10, more preferably at least ⅕, more preferably at least ⅓, more preferably at least ½ of the bars of each layer have a zigzag structure or a wiggled structure, whereas, preferably, all the other bars of said layer are straight bars; or   d) each n-th layer within said stack comprises bars that have a zigzag structure or a wiggled structure, wherein, preferably, at least 1/10, more preferably at least ⅕, more preferably at least ⅓, more preferably at least ½ of the bars of said each n-th layer have a zigzag structure or a wiggled structure, whereas, preferably, all the other bars of said each n-th layer within said stack and the bars of all other layers are straight bars,
 wherein n is an integer in the range of from 2 to 5, preferably 2 or 3, more preferably 2; or 
   e) 1/10, preferably ⅕, more preferably ⅓, more preferably ½ of the layers within said stack are layers that comprise bars having a zigzag structure or a wiggled structure, whereas, preferably, the other layers are layers that comprise only straight bars.   
     
     
         20 . The method according to  claim 1 , wherein said three-dimensional scaffold structure comprises a stack of multiple interconnected layers, each layer being composed of a plurality of parallel bars, wherein the layers within said stack are arranged such that the parallel bars of any layer X within the stack and the parallel bars of the layer subsequent to said layer X (i.e. layer X+1) form an angle of (180/n)°, wherein n is an integer in the range of from 2 to 10, preferably 2, and wherein the bars of the n-th subsequent layer with respect to a certain layer Y within the stack (i.e. layer Y+n) are offset with respect to the bars of said layer Y by a distance of 1/m times the distance between the parallel bars of said layer Y, wherein m is an integer within the range of from 2 to 5, preferably 2. 
     
     
         21 . The method of  claim 20 , wherein the bars of the layers within said stack are straight bars or the bars of the layers within said stack or the bars of every n-th layer within said stack have a zigzag structure or wiggled structure, whereas the bars of all other layers are straight bars. 
     
     
         22 . The method of  claim 1 , wherein said three-dimensional scaffold structure is formed from a shape-memory polymer (SMP). 
     
     
         23 . A method for tissue reconstruction in the body of a patient, comprising the following steps in order:
 a) implanting into said body of said patient at the site of intended tissue reconstruction an implant comprising a three-dimensional scaffold structure made of biodegradable material, wherein said three-dimensional scaffold structure comprises voids, and wherein said voids are filled with space-occupying structures that are removably attached to said three-dimensional scaffold structure and that are configured to prevent invasion of tissue and/or of individual cells into said voids;   b) after an incubation time period sufficient to allow for connective tissue and/or host vasculature to one or both of penetrate into the scaffold structure and invade the space that was occupied by the biodegradable scaffold structure at the time of implantation, removing the space-occupying structures from said voids within the biodegradable scaffold structure or from the tissue that has replaced the biodegradable scaffold structure during the incubation time period, thus generating void spaces not filled with space-occupying structures;   c) introducing transplantation cells into the void spaces not filled with space-occupying structures generated in step b).   
     
     
         24 . The method according to  claim 23 , wherein said voids are interconnected with each other and are arranged in a convergent geometric orientation radiating from one origin, or wherein the voids are not interconnected and are arranged in a non-convergent geometric orientation. 
     
     
         25 . The method according to  claim 23 , wherein said space-occupying structures are collapsible, wherein, preferably, said space-occupying structures comprise or consist of a liquid encased in a sheath that is impermeable to said liquid or a hydrogel encased in a sheath that is impermeable to said hydrogel. 
     
     
         26 . The method according to  claim 23 , wherein said space-occupying structures comprise or consist of ferromagnetic or superparamagnetic material, preferably of a composite of a biocompatible polymeric material, more preferably polycaprolactone, and of a biocompatible ferromagnetic material, more preferably iron oxide. 
     
     
         27 . The method according to  claim 23 , wherein said space-occupying structures are coated with a coating that prevents tissue attachment. 
     
     
         28 . The method of  claim 27 , wherein said coating is a coating which comprises a cell proliferation inhibiting drug, preferably a coating that comprises one or more of the drugs tacrolimus, everolimus and mitomycin c.