Patent Application
20070276506
The present teachings will become more fully understood from the detailed description and the accompanying drawings, wherein:
The following description of the various embodiments is merely exemplary in nature and is in no way intended to limit the present teachings, their application, or uses. It is understood that the present teachings can be used in any cartilage containing area of the body.
Referring to
The layer of cartilage 12 is generally a full-thickness layer of cartilage and includes the deep, intermediate, and superficial zones of the cartilage. The underlying bone 14 can comprise the subchondral bone and cancellous bone. The cartilage 12 and the underlying bone 14 are attached via a calcified cartilage layer.
The osteochondral plugs 10 can have a variety of shapes including any regular shape, such as the square plug of
The osteochondral plug 10 is freeze-dried and can have a water content of less than about 6% by weight. As used herein, the term “freeze-dried” or “lyophilization” and variants thereof, refers to the process of isolating the solid component of the osteochondral plug 10 from the water component by freezing the osteochondral plug 10 and evaporating the ice under a vacuum. The freeze-dried osteochondral plug 10 can have a final moisture level of less than about 6% by weight as recommended by the American Association of Tissue Banks.
The osteochondral plug can be demineralized to have a calcium content of less than about 8% by weight. As used herein, the term “demineralized” and variants thereof, means a loss or decrease of the mineral constituents or mineral salts of the individual tissues or bone relative to their natural state. In various embodiments, the demineralized osteochondral plug has a calcium ion concentration of less than about 1% by weight.
The osteochondral plug 10 can also include a tissue-health promoting agent. Tissue-health promoting agents are useful to expedite the integration of the osteochondral plug 10 into the surrounding tissues. Exemplary tissue-health promoting agents include nutrients, growth factors, bone marrow, undifferentiated cells, chondrogenic factors, osteogenic factors, and the like. In various embodiments, the tissue-health promoting agents can be selectively placed on the osteochondral plug 10. For example, it can be desirable to seed the underlying bone 14 with bone morphogenic proteins. In other embodiments, it can be desirable to seed the underlying bone with undifferentiated cells.
Referring to
A generic cutting instrument 22 depicted in
The donor tissue 20 is then demineralized to reduce the mineral content of the donor tissue. In various embodiments, demineralization can include reducing the calcium concentration in the donor tissue 20 to less than about 8% by weight. The demineralization can be achieved using a demineralizing agent. The demineralizing agent can be selected from acidification, for example, with acid-baths, chelating processes, for example, with chelator-baths, and combinations thereof.
Suitable acids include, but are not limited to, inorganic acids such as hydrochloric acid or organic acids such as peracetic acid. Chelating agents include, but are not limited to, disodium ethylenediaminetetraacetic acid (Na2EDTA). Exemplary calcium chelator agents can include any compound having chelating groups to which to adhere the calcium ions, such as 2,2′-Bipyridyl, Dimercaptopropanol, Ethylenediaminotetraacetic acid (EDTA), Ethylenedioxy-diethylene-dinitrilo-tetraacetic acid, Ethylene glycol-bis-(2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), Nitrilotriacetic acid (NTA), Salicylic acid, or Triethanolamine (TEA). In various embodiments EDTA and EGTA can be used to remove the mineral content from the donor tissue.
The time required to demineralize the donor tissue 20 can vary depending on the concentration of acid or chelating agent used, the displacement or flow of the solution and the desired final concentration of calcium in the donor tissue 20. For example, in an embodiment using hydrochloric acid, at an acid concentration of 0.1 to 2.0 N, the donor tissue 20 can be soaked in the acid bath for up to 10 days. The calcium or mineral concentration in the donor tissue 20 can be monitored by measuring the pH of the acid solution using a calcium specific electrode or a standard pH meter. In a preferred embodiment, the acid wash or soak ceases when the calcium concentration of the donor tissue 24 is less than about 8% or less than about 1%.
After demineralization, the pH of the donor tissue 20 is adjusted by removing the acid with a deionized/distilled water wash until the pH of the donor tissue 20 approximates that of the water. It is not outside of the scope of these teachings to expedite the neutralization of the donor tissue 20 using an ionic strength adjuster such as a biocompatible buffer solution. In embodiments having perforations or channels 16, the channels 16 can expedite the neutralization of the donor tissue by facilitating uptake of the wash water or buffer solution.
The demineralized donor tissue 20 can then be lyophilized to a moisture level of less than 6% by weight using standard drying techniques including, but not limited to, freeze drying, vacuum drying, air drying, organic solvent use, evaporation, and combinations thereof. The lyophilization preserves the donor tissue 20 and thereby creates the shelf-stable osteochondral plug 10 that is able to withstand degradation or compromises to the structural integrity of the final osteochondral plug 10. The variety of shapes provided can be preserved and used in case the anticipated needed size of the osteochondral plug 10 varies significantly from what a visual inspection of the defect site mandates.
In various embodiments, the demineralized osteochondral plug 10 can be placed inside of a sterilized dual chamber package. Packaging is preferably durable, flexible, has barrier resistance to moisture, chemicals, grease and bacteria, maintains its integrity upon exposure to low temperatures and is easy to handle in a medical or clinical setting. Suitable packaging materials can include materials selected from the group consisting of thermoplastic films, polyester films, para-aramid fibers, polyethylene fibers, and combinations thereof. In a preferred embodiment, the inner packaging includes a polyester film, such as Mylar® and a polyethylene fiber, such as Tyvek® (both DuPont, Wilmington, Deleware, USA) and the outer compartment is a moisture resistant foil bag made of aluminum and transparent plastic with a Tyvek® Header pouch. Moisture can be drawn from the filled Tyvek Mylar® aluminum/plastic chamber by lyophilizing, vacuum drying, air drying, temperature flux drying, molecular sieve drying and other suitable drying techniques. Preferably, moisture is removed by lyophilizing until the moisture content decreases to about 6% by weight. In various embodiments, the moisture level is less than about 6% by weight. The osteochondral plug 10 is “shelf-stable” in that it will not decompose over an extended period of time, such as 10 days, several months, or up to a year. At the time of surgery, the osteochondral plug 10 can be easily removed from the packaging and is ready for implantation in the defect site. It is understood that multiple osteochondral plugs can be processed simultaneously or the packaging of the plug can vary so long as the conditions in which the osteochondral plug 10 resides limit decomposition of the osteochondral plug 10 and bacterial colonization on the osteochondral plug 10.
A method of repairing a cartilage defect site 26 (or implant site) is provided. Exemplary articular cartilage defects include those caused by trauma, excessive use (such as sports injuries, for example) or diseases, including, but not limited to, osteoarthritis and osteochondrosis dissecans.
The defect site is prepared to receive the osteochondral plug 10. Preparing the defect site 26 can include providing an opening 36 in bone to receive the osteochondral plug 10. The defect site 26 can be shaped by the surgeon to provide the appropriate fit for the osteochondral plug 10. The defect site 26 can be prepared by removing the damaged cartilage with a burr, a curette, or a similar instrument. Once the damaged cartilage is removed down to the calcified cartilage, the size of the defect to prepare as subchondral bone is determined. It may be desirable to contour the subchondral bone region of the defect site to the same or larger dimensions than the cartilage defect region of the defect site. The edges of host cartilage should accommodate a secure press-fit or interference fit of the osteochondral plug 10 in the defect site 26. Bone is removed with a drill or cutting instrument that creates an opening having the same shape, size, and depth as the osteochondral plug 10 or an opening that is slightly smaller than the osteochondral plug 10. The defect site 26 can also be cleaned to provide a healthy tissue base upon which to place the osteochondral plug 10.
The osteochondral plug 10 is shaped. Shaping the osteochondral plug 10 can be achieved by shaving or otherwise trimming the osteochondral plug with a scalpel, surgical drill, or other cutting or resecting devices. In various embodiments, the defect site 26 is prepared such that the opening will provide an interference fit with the osteochondral plug 10.
The osteochondral plug 10 is applied to the implant site or defect site 26 using a press-fit or an interference fit. The osteochondral plug 10 is inserted into the opening 28 through the surrounding cartilage and bone such that the cartilage region 12 of the osteochondral plug 10 is arranged generally flush with the cartilage of the surrounding tissue. A flush osteochondral plug 10 facilitates appropriate articulation in the region. It is understood that the osteochondral plug 10 can be taller, wider, or deeper than the defect site 26 and can protrude above the plane of the surrounding tissue. A slight protrusion (less than about 10%) can allow settling of the osteochondral plug in the defect site 26.
Prior to implantation or after the osteochondral plug 10 is inserted into the opening 28, the demineralized osteochondral plug 10 can be hydrated with a hydrating fluid. The hydrating fluid can be an aqueous solution including, but not limited to, saline, water or a balanced salt solution (e.g., 140 ml NaCl, 5.4 ml KCl, pH 7.6). The aqueous fluids can include blood, blood products, platelet concentrate, solution(s) of growth factor(s), and combinations thereof. The fluids can be ambient fluids from the defect site or extra corpus fluids.
The osteochondral plug 10 can be hydrated by immersing the plug in the hydrating fluid. The hydrating fluid migrates into the pores of the osteochondral plug 10 and the system achieves near complete hydration in minutes, depending on the size of the osteochondral plug 10 and the relative viscosity of the hydration fluid. The hydrated osteochondral plug 10 can be placed directly into the defect site at the surgery or can be placed into a holding dish prior to use in a defect site.
As stated above herein, the osteochondral plug 10 can also include a tissue-health promoting agent. The tissue-health promoting agents can be sprayed or otherwise spread on the osteochondral plug 10 or the osteochondral plug 10 can be soaked in a solution containing the tissue-health promoting agent.
In various embodiments, it can be desirable to incorporate the tissue-health promoting agent into the hydration media. In still other embodiments, the health promoting agent can be incorporated into the osteochondral plug 10 prior to implantation, for example, a nutrient can be placed on the donor tissue 20 such that it is contained in the osteochondral plug 10 prior to arrival in the operating room.
The description of the present teachings is merely exemplary in nature and, thus, variations that do not depart from the gist of the present teachings are intended to be within the scope of the present teachings. Such variations are not to be regarded as a departure from the spirit and scope of the present teachings.
