Device for the formation of tissue and cell structures, especially bone regeneration by distraction

The invention relates to a device according to the preamble of Claim 1.

Method for bone regeneration by callus distraction are long been known. So the callus is also to build of the ridge used. Through progressive distraction bone segments bone formation is stimulated. In order to For example, in a ridge a bone stock for receiving an implant body to be created. It it is known that bone formation with a substantially Proliferation of osteoblasts, extracellular collagen and osteoid takes place. As the callus during fracture healing formed temporary tissue called. For the construction of Bone tissue are the osteoblasts responsible that a have diameters of about 20 micrometers. The osteoblasts form an organic matrix of collagen, which then calcified. Also known is the limb lengthening by callus distraction. Here are bone fragments distracted with example 1 millimeter per day. After Distraction there is a consolidation phase in which to the soft during distraction callus hardens.

From WO 01/91 663 of applicant discloses a device for Bone regeneration known by callus distraction, wherein the at regenerating bone created a membrane and which formed callus is subjected to mechanical stress. The device comprises tension means by which an adjustable exerted tension on the membrane and thus a bone regeneration induced by callus distraction. When callus is with this device, a callus between the stretched to regenerating bone and the membrane. The membrane is moved at a certain speed, for example, 1 millimeter per day. The speed is so set so that when a soft callus distraction can form, which then in a qualitatively satisfactory Bone transforms. Is the speed of distraction too fast, thus forming a substandard Callus and accordingly a little more stable bone. If the Distraction too slow, so hardened the callus and the membrane can not be moved, so the distraction not more could be done. The membrane is on one of the roughened bone-facing surface to form a compound to allow to an underlying bone. A bone remote surface is also roughened to peeling the membrane of a connective tissue covering to prevent.

By FR-2,753,366 A a jaw implant has become known, where a resorbable membrane is attached, which has a covering the implant receiving recess of a bone. The membrane is to allow bone regeneration. A callus but does not take place.

EP 0475077 discloses a membrane for bone regeneration, the resorbable or degradable polymeric and / or polymeric ceramic material contains. The membrane serves to form Callus to a bone. A callus is also in this case not take place.

Although the extreme importance of bone regeneration by callus distraction in particular for periodontology since long been known, could this using the callus but not yet prevail in practice.

The invention has for its object to provide an apparatus, a to provide membrane and a process that an even simpler and safer formation of tissue and cell cultures, and in particular allows bone regeneration by distraction. The invention to particular bone regeneration in the field paradontology allow.

The invention, in a generic device according to Claim 1 dissolved. Said means for biological liability osteoblast improve the anchoring of the callus at the Membrane significantly. This increased adhesion and thus anchoring of the callus on the membrane there is a much higher Certainty that the membrane during the distraction not from callus will be demolished. Thereby, it is also possible for the callus with the same forces to stretch as between two Knochenendstücken. The invention is not solely on the formation or regeneration limited by bone tissue, but for any kind of Tissue and cell cultures suitable. Namely, especially where Cell proliferation and differentiation by biomechanical stimulus transmission triggered the cytoskeleton and cell growth and tissue growth can be achieved, such as on a Endothelium.

The Means of biological adhesion of osteoblasts are in accordance a development of the invention anchor proteins on the Membrane attached. Protein molecules and in particular short-chain Protein molecules e ignen particularly suitable for adhesion or

Anchoring of osteoblasts. The liability is based on an adhesion between the protein molecules and the osteoblasts. The protein molecules preferably extend over the entire surface, facing the bone to be regenerated. In principle, also other means, in particular, organic Molecules conceivable which ensure the said liability.

According to a development of the invention it is provided that on of the fabric-facing surface of the membrane osteoblasts are located, the biological to the said means for Liability are anchored. The membrane is in this embodiment Thus already colonized by osteoblasts. Will the applied membrane to a to regenerating bone, so can thereby very quickly build a callus, which at the membrane is anchored by adhesion. Osteoblasts here preferably short-chain protein molecules by adhesion anchored.

The means for moving the membrane and thus the distractors are for a development of the invention mechanical tensile or Pressure medium. exhibit According to a development of the invention, the means for moving the diaphragm comprises at least one magnet, with the membrane a force and in particular a tensile force is applied. The membrane is this ferromagnetic provided material which is attracted by the magnet. Of the Magnet is preferably attached a distance from the membrane, for example to a tooth or to an implant.

The invention also relates to a membrane for forming tissue and cells in cell cultures and in particular for tissue regeneration and in particular the bone regeneration by callus distraction, wherein said membrane for the exchange of nutrients is translucent and has a surface which to a applying regenerating tissue and to move to the regeneration is. This membrane is thus characterized in that said Surface means for biological adhesion of osteoblasts having.

The membrane according to a development of the invention comparatively rigid so that they substantially without deformation can exert a tensile stress to a tissue.

According to a development of the invention, the membrane has a Carrier which is preferably made of metal, for example titanium is prepared. This carrier is preferably porous or forms a grid or a network that the renewing Callus is permeable to serum particular.

A particularly advantageous construction of the membrane is then obtained, when, according to one development of the invention, the support on a Surface is provided with a film-like layer, which is permeable for the exchange of nutrients. At this layer are in the region of the apertures of the carrier also Means of biological adhesion of osteoblasts arranged. Thus the whole of the bone can be regenerated facing Surface of the membrane with said means for biological Liability are provided. This results in a particularly high adhesion of the callus on the membrane.

The invention also relates to a method for forming tissue and cells in cell cultures and in particular for tissue regeneration and in particular bone regeneration, one of the to be regenerated exchange of nutrients permeable membrane with a Tissues or cells and particularly vital bone is connected and moved to regeneration. The method is inventively characterized in that the fabric or the cells or the bone facing surface of the membrane Means for adhesion of biological cells, and particularly comprising of osteoblasts, and that to the membrane to the forming Site is created, so that cells called the connecting means of the membrane and that subsequently the Cell forming the membrane at a certain speed of said location is moved away.

According to a development of the inventive method is provided that the membrane prior to the application on the cells facing surface with cells, and in particular osteoblast is provided. These cells or osteoblasts accelerate the Applying the membrane, for example, to the tissue or the bone callus formation. In addition, a particularly high adhesion the membrane on callus be achieved. When is distraction the membrane at a rate of 0.5 to 2 mm in day, and preferably at about 1 millimeter per day from the bone moved away. After completion of the distraction osteogenesis takes place a period of consolidation, during which the callus is converts into bone.

For bone regeneration or bone formation according to the invention is a membrane used, regenerating the vital and Bone substantially as a second vital bone appears. Callus formation between the membrane and the to regenerating vital bone is almost comparable a callus between two vital bone.

Embodiments of the invention will be described with reference to the Drawing explained. Show it:<dl tsize="10"><dt>Fig. 1</dt><dd>schematically to be regenerated, a section through a vital bone and an inventive Membrane,</dd><dt>FIG. 2</dt><dd>schematically a section through a vital bone and a membrane according to a variant,</dd><dt>Fig. 3</dt><dd>schematically a section through a vital bone and an inventive on this scale membrane</dd><dt>Fig. 4</dt><dd>is a schematic illustration according to FIG. 3, but later in time after a callus,</dd><dt>Fig. 5</dt><dd>schematically shows a section through an inventive Apparatus for bone regeneration using the example a bone regeneration in a posterior region,</dd><dt>Fig. 6</dt><dd>is a schematic illustration according to FIG. 5, but with a variant of the inventive device,</dd><dt>Fig. 7</dt><dd>a schematic perspective view of an inventive Device and a bone with this Device is regenerated,</dd><dt>Fig. 8</dt><dd>a view according to Figure 7, but after Regeneration,</dd><dt>Fig. 9</dt><dd>schematically shows a perspective view of a further variant, of the inventive apparatus and Bone, which is regenerated with this device,</dd><dt>Fig. 10</dt><dd>a view of Figure 9, but after regeneration, </dd><dt>Fig 11-13.</dt><dd>schematically illustrates the different structures of the membrane and</dd><dt>Fig. 14</dt><dd>diagrammatic, greatly enlarged section through the inventive membrane.</dd></dl>

Fig. 1 shows a vital bone 2, the surface of a is 21 to regenerate by callus distraction. The vital Bone 2 is intended particularly to the surface 21 to the bone formation to be animated. The bone 2 is any vital Bone, which is suitable for a callus, for example, is the vital bone 2 in such a posterior region.

The membrane 4 has a flat, disc-shaped form which adapted to the surface 21 of the vital bone and in two embedded gums. The membrane 4 can thus, as shown be flat or spatially shaped as example is shown in FIGS. 5 and 6. The membrane 4 is largely dimensionally stable and, for example, by deposits or reinforcing ribs stabilized, so that in this without substantial deformation a force, in particular a tension or pressure can be exerted. It is for this purpose of the WO 01/91 663 A1 Applicant pointed.

The membrane 4 has a flat layer 10 of nutrient liquid and in particular serum is permeable. The Layer 10 is in particular open-pored and has a thickness, which according to the structural requirements of the application directed. This thickness is generally in the range of 0.1 to 2 millimeters. The pores are micropores, not shown here, which are so far that it the passage of nutrients a nutrient solution allow. A substantial proportion of this Pore ​​preferably has a diameter of less than about 500 micrometers.

The layer 10 is surface connected to a carrier 13, the for example a plate or a grid or network of a suitable metal, in particular is titanium. The carrier 13 has a plurality of passages 14, which in a plate-shaped Education perforations. These passages allow 14 the passage of the nutrient liquid, the upper side of a 11 here penetrate the membrane 4 and a surface 15 can pass. The nutrient solution is in particular a serum. The lower limit of the diameter of these passages 14 is located in the The range of 5 microns to 25 microns. The support 13 may also be in the be integrated layer 10. In principle, however, a Embodiment is conceivable in which the carrier 13 is not available and the layer 10 stabilized by other suitable means is. It is conceivable, for example, stabilization by chemical Surface hardening.

The membrane 4 has a the vital bone 2 facing surface 15. On this surface 15 are means 16 for biological Adhesion of osteoblasts 17 applied. This means 16 have, for example, short-chain protein molecules on which to 1 have 30 carbon atoms. The means 16 preferably extend over the entire surface 15 and also into the passages 14. In these passages 14, these means 16 are also attached to the inside of the layer 10th The means 16 thus in the area of ​​the passages 14 also at an inner Surface 12 of the layer 10 is arranged. The means 16 are due the open porosity of the layer 10 and via the passages 14 supplied with nutrients. In one embodiment, in which the carrier 13 is not provided, the means 16 are directly applied to the surface 12th

Fig. 2 shows a membrane 4 ', the aforementioned except those mentioned Features still further comprises osteoblasts 18, which at the said means 16 adhere through adhesion. The osteoblasts 18 liable therefore. For example, on said short-chain protein molecules The osteoblasts can 18 by other suitable Cells replaced or supplemented.

Hereinafter, the use of the membrane 4 or 4 'as well as the Method for callus explained with these membranes.

In order to regenerate the bone 2 and for new bone to stimulate, the membrane 4 or 4 'is shown in FIG. 3 with the Surface 15 is applied to the vital bone. 2 Between the vital bone 2 and the diaphragm 4 thus forms a Layer S consisting of osteoblasts 17 of the vital bone 2 and Means 16 of the diaphragm 4 is formed. This layer is S due to the porosity of the layer 10 and the passages 14 with Nutrients supplied. These nutrients come example from a not shown here tissue over the membrane 4 is arranged. It is now essential that the osteoblasts 17 due to adhesion very quickly with the means 16, for example, connect with short-chain protein molecules. Thereby results very quickly a comparatively high adhesion the membrane 4 on the vital bone 2. In the case of the membrane 4 'contains the layer S also osteoblasts 18 of the membrane 4 '. These Osteoblasts 18 that the vital bone 2 thus across the membrane 4 'supplied, also improve the adhesion and accelerate callus formation. The membrane 4 'has on the surface 15 is substantially the properties of a vital bone. The vital bone 2 can thus the membrane 4 'little or no different from any other vital bone.

The layer S develops through osteoblast proliferation 17 and 18, to a schematically depicted in Fig. 4 Callus K. This callus K continues to be supplied with nutrients. Now is the known callus callus K stretched by the membrane 4 on in the directions of Arrows 20 exerted a force. This strain is on the callus K exerted a biological stimulus, the osteoblasts 17 and 18 and also newly formed osteoblasts 19 activated. The movement of the membrane 4 in relation to the vital bone 2 thus bone formation is induced. The speed, with which the membrane 4 is moved, is preferably steadily and is for example 0.5 to 2 millimeters in day. Due to the aforementioned adhesion of the means 16 on vital is bone in the callus and therefore during movement the diaphragm 4 is a detachment of the membrane 4 largely prevented. The said velocity of the diaphragm 4 is set to that during the callus, the callus K, can develop without hardening. If the speed is too slow, so hardened callus K and the membrane 4 can no longer be moved. the membrane 4 has reached the intended end position, so this is not moved further. In a subsequent Consolidation of the callus K transformed by mineralization into a solid bone around. The development of the Callus K during the callus distraction and during the consolidation phase For example, radiological or ultrasound to be controlled.

FIGS. 5 and 6 show an example of an application of the invention Membrane 4 in the field of periodontology. The Figures show a tooth 1, a vital bone 2, paradontales Fabric 3 and the periodontium 8. The membrane 4 is as above formed explained and also the membrane may be 4 '. It is located below the gum line 7 in the area of ​​vital Bone 2, the regenerated in the area of ​​a lesion 3 should. Said means 16 are provided on the underside of the membrane 4 or 4 'and the vital bone 2 facing. As can be seen, the diaphragm 4 is corresponding to the shape the bone 2 dome shaped. The callus is done Here, as explained above. The membrane 4 is in the Fig. 5 up and thus moved away from the vital bone. 2 To exercise the required force to the diaphragm 4 is on the tooth 1 a magnet 9 attached, which pulls the diaphragm 4 upwards. are thus exerted on the membrane 4, a magnetic force can containing these ferromagnetic materials. The membrane 4 can but also suitably contain parts that the magnet 9 be attracted.

In the embodiment of FIG. 6, the membrane 4 is mechanically with traction means 5 pulled upwards and thus the callus K stretched. The traction means 5 are rotatably mounted on the tooth 1 coil 5, on the wound, a thread 6 or a suitable wire is connected at a lower end of the membrane 4 is. The membrane 4 can be simultaneously with a plurality of such Coils 5 and 6 threads are stretched. In principle, the Membrane 4 but also pushed by suitable means from below will.

Figures 7 and 8 show a further embodiment of the the inventive device, with the bone 22 by means of a Callus is regenerated. The bone 22 has a Recess 23, for example, by removing a diseased bone part or caused by an accident. This recess 23 of the bone 22 is considerably weakened and it is with the inventive device now possible this recess 23 by callus distraction with stable to regenerate bone. For this purpose, a membrane 24 is in the Recess 23 used. The membrane 24 is plate-shaped and cut so that they can be seen in Figure 7, in which Recess 23 fits. The membrane 24 is for example, titanium manufactured and supply to the tissue to be enclosed bone permeable at least for serum, for example, open-pored educated. The membrane 24 is designed such that it is structurally stable. You may be charged in particular train, without being deformed thereby adversely. After all the membrane 24 at the bone-facing side 22 provided with a bioactive layer or surface which a relatively fast and firm anchoring of the bone 22 ensured at the membrane 24th The connection is made between facing the underside of the diaphragm 24 and this Surface 33 of the recess 23. Thus a secure callus and the establishment of stable bone tissue possible , the underside of the membrane 24 is formed as mentioned bioactive. In particular, the base is structured such that to anchor cells and in particular collagen fibers on the membrane can. The underside of the membrane 24 also preferably has Hydroxyl groups and / or amino groups in which the allow chemical compound to protein molecules, which 22 form bridges between the diaphragm 24 and the bone. These Protein molecules form chains having 1 to 30 carbon atoms. The to be connected to the underside of membrane 24 preferably has microstructures, Mesostructures and macro structures. The mesostructures have according to FIG 12 wells 45 of about 5-25 μ, on which dock 44 cells, particularly osteoblasts can. In the macro range are in accordance with Figure 13 wells 46 from about 100 to 1,000 μ, into which in particular Capillaries grow 47 and can anchor themselves therein. in the Microscale are provided according to FIG 11 wells 48, which are typically less than about 5 μ and in the example engage fibrin 49 and Eisweissmoleküle and can covalent chemical compounds OH, OH, OH arise. Said recesses 48 are due to the open pores the membrane 24 to the upper side of the membrane 24 is open and contained therefore serum which diffuse through the membrane 24 through can. As the Figure 11 shows clearly in this area Protuberances 50 present, the perpendicular from the membrane surface protrude and the anchoring in particular fibrin 49 improve. The growing into the recesses Cells and tissues are thus particularly for the tissue structure intensive metabolism always supplied with the necessary materials.

The membrane 24 is in the initial position shown in Figure 7 left until the membrane 24 is connected with the bone 22nd Then, on the diaphragm 24 in Figure 7 upwards and thus the Bone 22 away. For this purpose, a traction device 25 is provided, which has a bearing plate 26, the rod-shaped with two Proppants 27 is attached to the bone 22nd On the bearing plate 26 are two nuts 29 mounted in the respective Threaded rod 28 is screwed. These threaded rods 28 are pivotally connected at its lower end 28a with the membrane 24th If the two nuts 29 is rotated in the direction of arrows 30, so is applied to the membrane 24, a tensile force in the direction of arrow 34 exercised. Thus, the membrane 24 is moved upward. is new bone tissue between the membrane 24 and the bone 22 constructed, which is connected to the diaphragm 24th The speed, with which the diaphragm 24 is moved, is typically about 1 mm per day.

the membrane 24 has reached the position shown in Figure 8, so 23 is filled with newly formed bone tissue 32 the recess. This newly formed bone tissue 32 is still gelatinous soft, so that the membrane 24 be easily removed can. Bone tissue 32 now converts during a subsequent Consolidation time in a stable bone tissue around, so that the regenerated bone 22 'the desired strength receives.

Figures 9 and 10 show a further variant of an inventive Device for a callus. This device has two membranes 35, the same principle may be formed as the above-described membranes 4 and 24. The two membranes 35 are in a clearance 37 inserted between two bone parts 38 and 39 and at a Traction device 36 mounted so that it in the directions of arrows 40 can be moved toward each other. The membranes 35 in an initial position shown in Figure 9 as to bone surfaces 42 created that this explained above each connect with one of the membranes 35th Are the membranes 35 connected to the corresponding bone part 38 or 39, they are as mentioned by utilizing a train with appropriate Speed ​​moving toward each other. This bone tissue 43 constructed as indicated in FIG 10th If the two Membranes 35 are abutted, so that it does not move further may be, they will be removed. The bone tissue formed 43 is still soft and can be in the consolidation phase stabilize and grow together, so that finally a whole and resilient bone is present.

The figures 11 to 14 schematically show the surface structure the membrane 35 in increasing magnification. 11 shows the protuberances 50, in which the fibrin strands 49 can anchor the tissue to be regenerated. Figures 12 and 13 again show the anchorage of the cells 44 and fibrin 49 on the bioactive surface 15 of the membrane and the 14, the interconnecting pores 43, the passage to allow serum to the tissue and the vital tissue or Bone facing bioactive surface 15. The protuberances 50, the depressions 45, 46, 48, the above-mentioned at the surface 15 settled osteoblasts 18 and to the Surface 15 arranged and also the aforementioned protein molecules, are preferred agents for biological anchorage of the tissue or bone.

The membrane 35 is designed so that it adherent to the Cells forms only a few anchor points, the fluid exchange around these cells anchored but as little as possible Disabled. This allows to adverse concentration Nutrients and metabolisms be avoided. particularly suitable Process for the preparation of surfaces, in particular on a titanium membrane which satisfy the above conditions, are the plasma process and the silanization.

With the plasma process, the surface of the membrane can be removed and be modified or it can be on the surface thin coats. In the case of a membrane made of titanium can enhance the natural oxide layer, for example, or it can be applied chemical groups, for example, the binding of peptides are required. In the Plasma treatment, the surface is specifically with ions and radicals bombed, carrying enough energy in the surfaces to break bonds and make new ones. For patterning the surface may for example those with a tissue be covered. Before the plasma treatment the surface is cleaned with a suitable solvent and / or ultrasound. Treatment is beispielsweisein in a DIN A3 reactor. In acrylic acid hydrogen plasma we here for 30 Min. Coated to hydrophilicize the surface. The performance in the treatment amounted to 80 W at a process pressure totaling 0.1 mbar. On the treated surface is Carboxylabscheidung a layer having a thickness of, for example, 20 nm is formed to 280 nm. If in the plasma treatment used a woven fabric, then the layer thickness in the covered Range low. Investigations have shown that the pores the membrane is not substantially constricted by the applied layer will.

When silanization the membrane with functional silanes is, treated particularly Aminoalkyalkoxysilanen. The concentration the functional groups may in this case on the reaction parameters to be controlled. The functionalized surfaces be further modified. For example, on Thus, the hydrophilicity can be adjusted by positive or negatively charged interfaces are generated. For the silanization in particular membrane of titanium useful because to those in the presence of oxygen, a thin adherent Layer of titanium dioxide forms the stable covalent bonds results.

is as another method of treating the membrane surface the per se known layer-by-layer suitable. This method based on the fact that solids on its surface on contact with solvents such as water usually charges carry. Provides one such surfaces oppositely charged Polyion on, these ions are electrostatic Interactions and entropic effects bound. The resulting resulting surface can now gradually with further each oppositely charged polyion be modified. For the coating are a number of commercially available Polymers available. It can also be used Polylisin, the already known in monolayer as adhesion promoter is. By this method are particularly stable and homogeneous reaches layers.

The invention is also suitable for the distraction of cell cultures in biological laboratory. The appropriate here Distraktionsfrequenzen are here in general, however, substantially smaller than in the Callus. This can, for example, several micrometers per day, For example, 1 micron per day, respectively. The Distraktionszeit is usually correspondingly longer and can even several days or be months.

It can be distracted cells in vitro and in vivo. You can choose between two membranes and thus in two directions be distracted. Cells that are distracted, are in the Usually highly stressed. Such cells can be due to the high Stress die. In order to avoid this, is a conditioning practical with suitable nutrient medium.

LIST OF REFERENCE NUMBERS

<dl tsize="3" compact="compact"><dt>1.</dt><dd>tooth</dd><dt>. 2</dt><dd>bone</dd><dt>. 3</dt><dd>tissue</dd><dt>. 4</dt><dd>membrane</dd><dt>. 5</dt><dd>traction means<dl tsize="2" compact="compact"><dt>5 '</dt><dd>Do the washing up</dd></dl></dd><dt>. 6</dt><dd>thread</dd><dt>. 7</dt><dd>gums</dd><dt>8th.</dt><dd>periodontium</dd><dt>. 9</dt><dd>magnet</dd><dt>10th</dt><dd>layer</dd><dt>11th</dt><dd>fibrin</dd><dt>12th</dt><dd>surface</dd><dt>. 13</dt><dd>carrier</dd><dt>14th</dt><dd>crossings</dd><dt>15th</dt><dd>surface</dd><dt>16th</dt><dd>medium</dd><dt>17th</dt><dd>osteoblasts</dd><dt>18th</dt><dd>osteoblasts</dd><dt>19th</dt><dd>osteoblasts</dd><dt>20th</dt><dd>osteoblasts</dd><dt>21st</dt><dd>surface</dd><dt>22nd</dt><dd>bone</dd><dt>23rd</dt><dd>recess</dd><dt>24th</dt><dd>membrane</dd><dt>25th</dt><dd>traction means</dd><dt>26th</dt><dd>bearing plate</dd><dt>27th</dt><dd>proppant</dd><dt>28th</dt><dd>threaded rods<dl tsize="4" compact="compact"><dt>28.a</dt><dd>lower end</dd></dl></dd><dt>29th</dt><dd>mother</dd><dt>30th</dt><dd>arrow</dd><dt>31st</dt><dd>arrow</dd><dt>32nd</dt><dd>bone tissue</dd><dt>33rd</dt><dd>surface</dd><dt>34th</dt><dd>arrow</dd><dt>35th</dt><dd>membrane</dd><dt>36th</dt><dd>traction means</dd><dt>37th</dt><dd>clearance</dd><dt>38th</dt><dd>bone part</dd><dt>. 39</dt><dd>bone part</dd><dt>40th</dt><dd>arrows</dd><dt>41st</dt><dd>bone tissue</dd><dt>42nd</dt><dd>capillaries</dd><dt>43rd</dt><dd>interconnecting pores</dd><dt>44th</dt><dd>cell</dd><dt>45th</dt><dd>wells</dd><dt>46th</dt><dd>wells</dd><dt>47th</dt><dd>capillaries</dd><dt>48th</dt><dd>wells</dd><dt>49th</dt><dd>fibrin</dd><dt>50th</dt><dd>protuberances</dd><dt>51st</dt><dd>medium</dd></dl><dl tsize="1" compact="compact"><dt>S</dt><dd>layer</dd><dt>K</dt><dd>callus</dd></dl>