Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/14—Macromolecular materials
  • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
  • A61L27/225—Fibrin; Fibrinogen
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
  • A61L27/362—Skin, e.g. dermal papillae
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
  • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
  • A61L27/60—Materials for use in artificial skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2400/00—Materials characterised by their function or physical properties
  • A61L2400/06—Flowable or injectable implant compositions

Definitions

• the present invention relates to injectable allogenous fillers (acellular dermal matrix or fascia) for the removal of wrinkles and the correction of facial contours, which are made from an allogenous dermis.
• the present invention is concerned with the morphology of the injectable allogenous fillers.
• Fillers function to fill defects within the skin and subcutaneous tissue by inducing soft tissue augmentation in the defects when injected into sites of the defects, and are typically used for the removal of wrinkles and the correction of facial contours.
• Filler materials include biological tissues and synthetic compounds such as polyacryl amide, polyethylene etc. Synthetic filler materials do not induce allergic responses to neterogenous proteins in the body, and are not absorbed by the body over time and, thus, provide a permanent correction. However, there is a significant disadvantage with the synthetic filler materials, as follows. The synthetic fillers are difficult to remove after being implanted, and infiltrate adjacent tissues. Thus, when a synthetic filler is not implanted normally, an applied area of the skin is difficult to restore. Thus, the synthetic filler grafting should be performed with particular caution.
• autologous filler materials which are prepared from patient's own tissues, such as autologous fat or dermis, do not induce allergic responses after being implanted because the filler materials are biological tissues taken from the patient.
• this procedure has a disadvantage in that autologous implants must be isolated from the patient own tissues before grafting.
• the allogenous dermal matrix or fascia are prepared by removing the epidermis and immunogenic cells in the dermis from the skin of allogenous donor or cadavers. Since the noncellular components of the dermis, consisting primarily of extracellular matrix proteins and collagen, that is, collagen fibers, have been demonstrated to be relatively nonimmunogenic, the allogenous dermal matrix or fascia have no risk of iinmunological rejection and infection.
• acellular dermal graft was developed in 1991 in the U.S.A. for the treatment of burn wound sites. Thereafter, acellular dermal grafts have been widely used for cosmetic purposes, such as the removal of wrinkles around the lips, rhinoplasty, the removal of scars, and some burn cases.
• the graft becomes repopulated with the patient own cells, that is, fibroblast cells, and is revascularized in such a manner that the fibroblast cells generate new collagen fibers while the implanted collagen fibers are removed by immune cells.
• acellular dermal grafts are totally replaced by native fibroblast cells after having been implanted for a predetermined period, they overcome the problem encountered in the synthetic fillers, that is, the difficulty in graft removal.
• the implantation must be performed again.
• Implanting an allogenous graft into the site of a defect in the skin to correct wrinkles or facial contours or to augment soft tissues is performed using one of two major methods. One is based on making an incision at the site of a defect in the skin with a surgical operation and inserting a strip- type allogenous graft at the site through the incision. The other is based on processing an allogenous graft into a micronized form and injecting the resultant micronized graft into a patient.
• the synthetic and biological fillers have several problems to be solved with respect to allergic responses to heterogeneous proteins, a simple surgical procedure, a long-lasting effect, and the like.
• simplification of a surgical procedure is difficult to achieve simultaneously with the long- lasting correction effect.
• AlloDerm which is an acellular human dermal graft, as shown in FIG. 1, was processed into an injectable form of particles 2 mm long 2 mm wide.
• the AlloDerm particles were injected using a syringe with a 16- or 18-gauge needle, this particulate form was found to have a correction effect similar to the case of inserting an acellular dermis in a strip, and the correction was proven to last for several years.
• the syringe with a 16- or 18-gauge needle was used for the following reasons. Since facial skin is generally about 1 mm thick, subcutaneous injection of acellular dermis using a syringe with a greater-gauge needle results in a relatively thick acellular dermal layer being formed compared to the adjacent skin, thereby making the skin surface uneven or causing indentation. In addition, a syringe with a large gauge needle entails a large correction locus which is susceptible to edema as and readily visible with the naked eye.
• an object of the present invention is to provide an injectable acellular filler having a morphology enabling an injection pressure that allows fine control of the injection amount thereof.
• an injectable acellular filler which is prepared by processing an acellular dermis into the form of particles, wherein the particles each have a streamlined shape having a head and tail narrower than the body, and the body is 1.5 mm to 2.3 mm wide and 4 mm to 8 mm long.
• the streamlined shape of the particles is an almond shape which is somewhat extended at both its head and tail portion so as to have pointed ends.
• the streamlined shape of the particles may be a longitudinal hexagonal shape.
• the streamlined shape of the particles may be a longitudinal octagonal shape having a rod-shaped piece at an upper or lower side of an octagon.
• the filler is admixed with fibrin.
• the injectable acellular filler of the present invention has a morphology allowing fine control of the injection amount of the filler, thereby enhancing the accuracy of the filler injection.
• the present filler has an effect of enhancing augmentation of the skin or soft tissue, thereby providing more satisfactory results.
• the present filler is arranged upon injection in a manner of allowing the top, bottom and side surfaces of an acellular dermis to mix, it has an increased engraftment capacity.
• the present filler allows an applied site in the facial skin to move naturally before the filler injected is engrafted into a patient.
• FIG. 1 shows an acellular dermal graft, AlloDerm, processed into a particulate form in which each particle is 2 mm long 2 mm wide;
• FIG. 2 shows an injectable acellular filler according to a first modification of an embodiment of the present invention, which is prepared by patterning an acellular dermal graft, SureDerm, into particulate form in which each particle has a streamlined shape, especially, a rice grain shape;
• FIG. 3 shows an injectable acellular filler according to a second modification of the embodiment of the present invention, which is prepared by patterning a SureDerm sheet into a particulate form in which each particle has a streamlined shape, especially, a longitudinal hexagonal shape having the same size as in FIG. 2;
• FIG. 4 shows an injectable acellular filler according to a third modification of the embodiment of the present invention, which is prepared by patterning a SureDerm sheet into a particulate form in which each particle has a streamlined shape, especially, a longitudinal octagonal shape, having the same size as in FIG. 2, wherein the upper or lower side of the octagon has a thin rod-shaped piece;
• FIG. 5 shows the application of the injectable acellular filler of FIG. 2 to the site of a defect in the facial skin
• FIG. 6 illustrates the relationship between the width of particles of an injectable acellular filler, according to the present invention, and skin augmentation, when the filler is injected into a subcutaneous fat layer;
• FIG. 7 shows an array of particles of an injectable acellular filler according to the present invention, in which each particle is arranged in an upward direction of a top surface thereof;
• FIG. 8 shows another array of particles of an injectable acellular filler according to the present invention, in which each particle is arranged in an upward direction of a top surface, a bottom surface or a side surface thereof, so that the surface of the array includes all of the top, bottom and side surfaces of the particles;
• FIGS. 9 and 10 are pictures, taken with a transmission electron microscope, showing a mouse dermis stained with hematoxylin-eosin 6 weeks after the injection of the filler of the present invention thereinto,
• FIGS. 11 and 12 are pictures, taken with a transmission electron microscope, showing a mouse dermis stained with hematoxylin-eosin 13 weeks after the injection of the filler of the present invention thereinto;
• FIG. 13 is a picture, taken with a transmission electron microscope, showing a mouse dermis stained with hematoxylin-eosin 32 weeks after the injection of the filler of the present invention thereinto;
• FIGS. 14 and 15 are pictures, taken with a transmission electron microscope, showing the nascent fibroblast cells generated between the filler particles of the present invention, and the nascent collagen fibers generated by the fibroblast cells and the collagen fibers of the filler, respectively.
• the present invention provides an injectable acellular filler processed into a particulate form in which each particle has a streamlined shape from 1 mm to 2.3 mm wide and 4 mm to 5.5 mm long.
• FIGS. 2 to 4 show injectable acellular fillers according to an embodiment of the present invention, which are prepared by processing an acellular dermal graft, SureDerm or AlloDerm, into the streamlined shape.
• FIG. 5 shows the application of the filler shown in FIG. 2 to the facial skin.
• FIG. 6 illustrates volume augmentation of the skin according to the width of a filler when the filler is injected into a subcutaneous fat layer.
• FIG. 7 shows an array of particles of an injectable acellular filler according to the present invention, in which each particle is arranged in an upward direction of a top surface thereof.
• FIG. 8 shows another array of particles of an injectable acellular filler according to the present invention, in which each particle is arranged in an upward direction of a top surface, a bottom surface or a side surface thereof, so that a surface of the array includes all of the top, bottom and side surfaces of the particles.
• an acellular dermis is prepared by removing the epidermis and immunogenic cells in the dermis from the skin of cadavers.
• Available acellular dermal grafts vary in size according to their isolation site from the skin, but are typically about 1 mm thick and are typically 2 cm wide and 7cm long or 3 cm wide and 7 cm long.
• FIG. 2 shows an injectable acellular filler according to a first modification of the embodiment of the present invention, which is prepared by patterning a SureDerm sheet 2 cm wide ' 7 cm long into a particulate form in which each particle has a streamlined shape, especially, an almond shape, 1.5 mm to 2.3 mm wide and 4 mm to 8 mm long.
• the filler is an almond shape with pointed ends at the head and the tail. This pointed almond shape allows the acellular dermal graft to be patterned with a minimal loss.
• FIG. 3 shows an injectable acellular filler according to a second modification of the embodiment of the present invention, which is prepared by patterning a SureDerm sheet into a particulate form in which each particle has a streamlined shape, especially, a longitudinal hexagonal shape having the same size as in FIG. 2.
• FIG. 4 shows an injectable acellular filler according to a third modification of the embodiment of the present invention, which is prepared by patterning a SureDerm sheet into a particulate form in which each particle has a streamlined shape, especially, a longitudinal octagonal shape, having the same size as in FIG. 2, wherein the upper or lower side of each octagon has a thin rod-shaped piece.
• particulate filler is rehydrated for a predetermined period and is injected into a subcutaneous fat layer using a syringe.
• the filler rehydration must be carried out for a period sufficiently long to maintain the innate viscosity of the skin, thereby reducing the injection pressure of the filler particles.
• the injection amount of the filler is easy to control, and the fillers become tender so as to be stacked without dead spaces.
• the present inventors prepared patterned fillers having various shapes, performed rehydration of the fillers for 20 minutes, and evaluated the fillers for the volume augmentation effect. As a result, the fillers having the above-mentioned shapes were found to have excellent efficacy on wrinkle removal or facial contour corrections.
• the filler passes through a syringe in two major steps: loading the filler into the needle of the syringe; and pressing down the plunger unit of the syringe to pass the filler through the needle.
• the pressure at the first step is higher than that at the second step.
• each filler particle has a width greater than 2.3 mm, a pressure higher than 0.41 kgf/cm is sensed when the filler passes through a 16-gauge needle, and the difference in pressure between the (stoppage and passage) of each filler particle increases.
• each filler particle is shot at such high speeds as to have bad influence on the distribution and shape of the filler particles injected thus far. As a result, the filler particles injected cannot be evenly distributed, but aggregate.
• the filler preferably comprises particles each of which is less than 2.3 mm in width.
• each filler particle is narrower than 2.3 2 mm, its injection pressure is not always lower than 0.41 kgf/cm .
• the injection pressure of the filler may vary depending on the shape of the particles of the filler. For example, if each particle of the filler is 2 mm 2 wide and has a rectangular shape, its injection pressure exceeds 0.41 kgf/cm , and thus, this filler is not suitable for injection. For this reason, the present invention suggests that filler be processed into a particulate form in which each particle has a streamlined shape. When filler was processed into a streamlined particulate form and then injected, its injection pressure was found to remarkably decrease, thereby increasing accuracy upon grafting.
• streamlined shape refers to a morphology in which each filler particle has a head and tail narrower than the body of the particle.
• the narrower head and tail facilitate the passage of the particles of the filler through a syringe needle, and the wide body has the effect of increasing soft tissue augmentation.
• ⁇ 6i> As shown in FIG. 2, when filler is patterned into a particulate form in which each particle has an almond shape, the loss of acellular dermis upon the patterning may be minimized. Particularly, the almond shape is somewhat extended at both the head and the tail portion so as to have a pointed end at both the head and the tail. This extended almond shape allows the acellular dermis graft to be patterned with a minimum loss. The minimized loss of the expensive acellular dermis means that increased volume augmentation can be achieved at the same cost, thereby reducing surgical operation costs.
• filler is injected into a subcutaneous fat layer using a syringe having a 16-gauge needle.
• a filler injection space is primarily formed by pricking the subcutaneous fat layer with the needle.
• the filler is injected by pressing a plunger unit of the syringe down into the space while simultaneously moving the needle back.
• the filler is typically injected in lines about 7 mm away from each other at the site of a defect in the skin.
• the filler injection space is formed in three lines.
• the syringe needle is pricked into a site a predetermined distance from the site of the defect in the skin, and is subsequently inserted along each line to provide a filler injection space by changing the angle between the needle and each line, taking skin elasticity into consideration. Therefore, only one puncture wound remains on the skin.
• the formed filler injection space is about 1.295 mm in diameter.
• FIG. 6 when a filler comprising particles wider than the diameter of the filler injection space is injected into the filler injection space, it is swollen upwardly by the pressure from both side areas along the line of the filler injection space, thereby augmenting the application area of the skin in a vertical direction (as noted above, particles of the filler are limited to 1 mm in thickness).
• the skin or soft tissue augmentation increases with the width of particles of the filler.
• the facial skin is about 1 mm thick, the injection of filler comprising extremely wide particles results in the skin surface becoming uneven.
• the injectable acellular filler is limited in the width of particles thereof to a degree not causing excessive unevenness of the skin surface. A thickness less than 2.3 mm is preferable.
• filler particles are less than 1.5 mm in width, two of the particles are likely to be present together in a side-by-side fashion in a 16- or 18-gauge syringe needle. In this case, the filler particles cannot pass through the needle, thereby making grafting impossible. For this reason, filler particles are preferably 1.5 mm to 2.3 mm wide.
• the filler particles are preferably arranged to orient theh top surface of each of the particles upwards .
• filler is arranged in such a way that the top, bottom and side surfaces of an acellular dermis are randomly mixed, and, as a result, all kinds of surfaces are arranged to contact the skin of a patient .
• the filler particles are wider than 2.3 mm, the particles are arranged in such a way that side surfaces thereof seldom contact the skin of a patient.
• the result is closely related to the fact that an available acellular dermis is about 1 mm thick as described above.
• the filler particles have a thickness of about 1 mm, less than the width thereof.
• the particles are wider than 2.3 mm, they are difficult to stand vertically relative to the side surface thereof, and tend to incline. Eventually, the particles fall down, and the top or bottom surface thereof comes into contact with the skin. That is, the side surface of the particles of the filler seldom has a chance to contact the skin.
• the particles of the injectable acellular filler of the present invention are preferably smaller than 2.3 mm in width.
• the injectable acellular filler of the present invention will be described with respect to the length of the particles thereof in relation to the augmentation effect at a site of a defect in the facial skin and the natural movement of the site after grafting.
• Each of the particles of the filler acts like a single plate. However, because they are arranged in a partially overlapping fashion, the particles move like a single body due to the overlapping regions, thus allowing the applied site of the facial skin to move naturally when filler particles are shorter than 8 mm.
• the particles of the injectable acellular filler are preferably maintained shorter than 8 mm to retain natural movement of the applied skin site.
• particle length shorter than 4 mm results in a cumbersome injection process and reduced volume augmentation.
• the injectable acellular filler of the present invention may be used in general facial plastic surgery for facial contour corrections, for example, in the ears, a site below the ears, the cheekbones, the temple, a site below the nose, the lips, the jaws and the brow.
• the fillers can be injected into various layers including subcutaneous layers, hypodermic layers, muscular layers and periostea, according to the degree of adaptation, so that proper control of the volume augmentation can be achieved, effectively correcting facial contours.
• the present filler may vary in the injection site and the injection amount according to the areas to be corrected in the facial skin, but the present technical idea, that is, the morphology and size of the particles of the filler, remain the same.
• an 18-gauge syringe needle is preferably used because the skin in the temple is thinner than other areas of the facial skin, and the filler is about 1.5 mm wide and about 4 mm long. This size of the filler falls within the width and length ranges limited in the present invention.
• the next embodiment comprises a mixture of the filler having the shape according to the present invention with fibrins, wherein the effect of soft tissue augmentation is sustained for as long as possible.
• an anticoagulant is added to 10 cc of whole blood taken from a target, followed by centrifugation for 10 min. After being separated from the centrifuged whole blood, the plasma is mixed with thromboxane to form fibrins. These are further mixed with the acellular dermis or myofascia having the size and shape of the present invention and the resulting mixture is injected into a defect site.
• the mesh form of the fibrins prevents the recollagenation of the acellular dermis (AlloDerm, SureDerm) or myofascia so as to retard the absorption of the filler into the body, extending the time for which the effect of soft tissue augmentation is sustained.
• FIGS. 9 and 10 are TEM photographs showing the fillers of the present invention, stained with hematoxylin-eosin 6 weeks after injection into a murine sub-dermal layer of a mouse.
• FIG. 9 shows fillers injected into the sub-muscular portion of a mouse along with the epidermis and the muscle while FIG. 10 is a magnified view of FIG. 9.
• the injected filler particles have outer circumferential boundaries that are dyed redder than other portions. These dark red portions are attributed to the nascent collagen fibers generated by the infiltration of the fibroblast cells, indicating that the infiltration of fibroblasts into the injected filler particles begins at the circumference of the filler particles.
• the fillers having the size according to the present invention have the advantage over conventional powdered fillers of retarding the infiltration of fibroblast cells.
• the fillers of the present invention allow the replacement of collagen fibers to be conducted slowly because their surface area is smaller than that of conventional powdered fillers.
• the collagen fibers generatd by fibroblast cells cause rigid skin texture, like scar tissue, rather than normal skin resilience because they are small and dense compared to normal skin.
• the infiltration of fibroblast cells proceeds slowly, with the concomitant retardation of the replacement with the nascent collagen fibers, resulting in the maintenance of a natural sense of skin touch for a prolonged time period.
• FIGS. 11 and 12 are TEM photographs showing the fillers of the present invention, stained with hematoxylin-eosin 13 weeks after injection into a murine sub-dermal layer of a mouse.
• FIG. 11 shows fillers injected into the sub-muscular portion of a mouse along with the epidermis and the muscle while FIG. 12 is a magnification of FIG. 11.
• FIGS. 11 and 12 show the outer circumferential boundaries, dyed redder than other portions, are attributable to the nascent collagen fibers generated by the infiltration of the fibroblast cells, as in FIGS. 9 and 10.
• FIG. 13 is a TEM photograph showing the fillers of the present invention, stained with hematoxylin-eosin 32 weeks after injection into a murine sub-dermal layer, together with adjacent epidermis and muscle portions. The portions dyed redder than other portions are attributable to the nascent collagen fibers generated by the fibroblast as in FIGS. 9 and 10.
• the fillers having the shape and size according to the present invention show far greater persistency of soft tissue augmentation than do the conventional powdered fillers. This is, as described in FIGS. 9 and 10, attributable to the fact that because the infiltration of fibroblast cells into the injected fillers starts at the boundaries of the filler particles, phagocytosis of the injected filler particles and replacement with nascent collagen fibers proceed at far lower speeds on the fillers having the shape and size according to the present invention than on powdered fillers having larger surface areas.
• FIG. 14 is a TEM photograph showing the fibroblast cells generated between the filler particles of the present invention
• FIG. 15 is a TEM photograph of the collagen fibers of the injected filler particles and the nascent collagen fibers generated by fibloblast cells, showing the progress of the infiltration of fibroblast cells into the injected filler particles and the replacement with the nascent collagen fibers over time.
• FIG. 14 From FIG. 14, it is apparent that fibroblast cells are generated among the injected filler particles and collagen fibers start to infiltrate at the circumference of the injected filler particles.
• ⁇ 96> As seen in FIG.
• the collagen fibers of the injected filler particles are maintained at somewhat regular intervals in relatively sparse amounts while the nascent collagen fibers generated by the fibroblast cells have small and dense textures.
• the collagen fibers newly generated by the fibroblast cells have a rigid texture like that of scarred skin, a natural skin texture cannot be maintained for a long period of time if the replacement with the nascent collagen fibers rapidly proceeds.
• the fillers having the shape and size according to the present invention allow only slow replacement with new collagen fibers and therefore can maintain a natural sense of skin touch for a longer period of time than can the conventional powered fillers.
• the injectable acellular filler of the present invention may be used in general facial plastic surgery for facial contour corrections, for example, in the ears, a site below the ears, the cheekbones, the temples, a site below the nose, the lips, the jaws and the brow.
• the fillers can be injected into various layers including subcutaneous layers, hypodermic layers, muscular layers and periostea, according to the degree of adaptation, so that proper control of the volume augmentation can be achieved, effectively correcting facial contours.
• the present filler may vary in the injection site and the injection amount according to the areas to be corrected in the facial skin, but the present technical idea, that is, the morphology and size of the particles of the filler, remain the same. ⁇ o ⁇ > Although a preferred embodiment of the present invention has been described for illustrative purposes, those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

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• 2005
  • 2005-06-03 KR KR1020050047741A patent/KR100680134B1/ko not_active IP Right Cessation
  • 2005-06-10 WO PCT/KR2005/001745 patent/WO2005120597A1/en active Application Filing

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