1. Field of Invention
This invention relates to the treatment of injured tissues within human or animal bodies, specifically to the way injured tissues are joined and the way macromolecules are directed to promote healing. The invention can be modified such that a treating material, when affixed to a major surface of the minimally-porous sheet, can be directed preferentially to the site of injury. Although I will frame this invention initially in terms of treatment of traumatic injuries, I will also discuss this invention in the treatment of many other conditions including treatment of metastases, infections, metabolic conditions such as osteoporosis, primary neoplasms, and vascular disease.
2. Description of Prior Art
Traumatic injury remains the single most important contributor to long-term disability among working-aged persons. Because the costs of rehabilitation and the loss of productivity during recovery are great, additional ways to decrease "down time" following injury are continually being sought. Although many tissues are commonly fractured in traumatic injury, e.g., the liver, the kidney, the bowel, the bladder, the spleen and the testicle, perhaps the most often-injured tissues are the bones.
Currently used techniques of bone fracture fixation:
When tissue is injured, a surgeon must first decide whether the patient needs an operation to fix the injury. Closed reduction refers to a non-operative method of fracture fixation whereby a surgeon manipulates the fractured internal structures into anatomic alignment from outside the body. Many simple bone fractures are treated in this way. After closed reduction, the surgeon casts the extremity, and the bone is left to heal. Serious bone fractures cannot be treated by closed reduction. These fractures either involve shattered bone (comminuted fractures), or involve bones critical to support of the axial skeleton such as the spine, pelvis, and/or the femur. These bones usually will not heal unless they are fixed in position in the operating room using the technique of internal fixation. Since this invention deals with a method of internal fixation, I will discuss internal fixation with respect to treating bone fractures in more detail.
Internal fixation of bone fractures, as it is currently practiced, involves exposing the fracture and affixing a rigid stabilization device to the bone. The current state of the art is to approximate the fragments and then bridge the site of injury with a rigid rod or plate such that force is transmitted across the device and not the small fragments. The hope is that new bone will form between the small fragments and ultimately bridge between the small fragments and the major fragments. If the major fragments do not join, it is termed "non union". A good result is when bony bridging occurs rapidly between large and small fracture fragments. Unfortunately good results are relatively rare and, in complicated bone fractures, reoperation and refixation are usually the rule. Fractures that require a second and sometimes third and fourth operation rarely heal well, and the patient is left with permanent deformity. Consequently, it is critically important to get the operation right the first time.
Complex fractures often heal with poor results:
The reasons complex bone fractures do not heal well are unknown; however several studies have shown that a cascade of both molecular and cellular events is initiated once tissue is injured, and that for some reason in severe injuries, this cascade is interrupted.
Following injury, specific proteins are made by injured cells and are secreted into the interfragmentary space. When an adequate concentration of these macromolecules is attained within the interfragmentary space, osteoblasts and fibroblasts are recruited and a "scaffolding" is constructed. If the concentration of these growth-promoting molecules within the interfragmentary space remains high enough, a cellular matrix is laid upon the scaffolding and, if the patient is lucky, the tissue is healed.
When the patient is not as lucky, the small bone fragments resorb, i.e., are biodegraded by host enzymes, leaving a gap between major fragments. Small bone fragments are naturally resorbed unless they are bathed in an adequate concentration of growth-promoting macromolecules. The patient subsequently has a defect between proximal and distal fracture segments. Surgical intervention is subsequently required for bone grafting to maintain limb length. If the limb-lengthening procedure fails, which is often the case, non-union results. Non-unions very rarely heal with an acceptable physiologic result and as a consequence, they are a very common reason for malpractice lawsuits. Not surprisingly, non-union is one of the most feared long-term complications in orthopedic surgery.
Often during bone fracture healing, bone growth factors produced by the injured cells diffuse into surrounding muscles. The efflux of growth-promoting proteins from the fracture site into the soft tissues is harmful for at least two reasons. First, there results a lower concentration of growth factors bathing the fracture fragments. Second, because bone growth factors stimulate bone growth, the diffusion of bone growth factors into surrounding muscles causes bone to be formed within them (heterotopic bone). Because, heterotopic bone can limit range of motion within that muscle for the life of the patient, it too is a major cause for clinical concern.
The problems of non-union and heterotopic bone formation have been recognized for well over a hundred years, and are now thought to be a result of two major factors. First, there becomes a paucity of growth-promoting molecules in the interfragmentary space during a critical stage of healing. Even well-aligned and well-approximated fragments resorb when there are insufficient growth-promoting macromolecules within the interfragmentary space. Second, the movement of small fragments out of the plane of the fracture increases the distance that must be bridged by new bone. Heterotopic bone is formed when these bone growth macromolecules diffuse into neighboring soft tissues. Orthopedic surgeons have tried to prevent non-union and heterotopic bone formation in a number of ways, and the most significant and relevant of these will be discussed below.
Compression plate fixation:
The simplest internal fixation device currently in use is the compression plate. Compression plate fixation involves bridging the fracture with a rigid bar of metal that has been fixed to the major fragments. Although adequate for simple transverse fractures, a plate is unable to secure shattered bone because fragments are often small size and "free-floating" within the fracture cavity. Furthermore, compression plates are unable to contain the macromolecules produced by the fracture fragments. Rigid plates, since they are not flexible in three dimensions, cannot cover a fracture in a continuous fashion even if they are laid close together. Consequently, growth-promoting macromolecules and small fragments can diffuse around them and into the surrounding soft tissues.
Moreover, compression plates remove virtually all stress at the sites they are affixed such that the hardest bone, i.e., the cortex, becomes "spongified" increasing the risk of refracture. This effect is most pronounced the longer the plate is in place. One of the reasons that spongification is thought to occur is that the compression plate is unable to restrain a high enough concentration of bone growth factors at the plate-bone interface.
Intramedullary rod fixation:
Another common method used to fix complex long bone fractures is using an intramedullary (IM) rod. IM rod fixation involves pounding a rigid bar down the medullary cavity such that it bridges the fracture. Although IM rod fixation has the benefit of not having to expose the fracture site itself, the process of IM rod insertion is very traumatic to the bone. IM rods displace small fragments and disrupt the medullary blood supply; and because there is no mechanism to restrain either small fragments or macromolecules produced by the fracture, small fragments are free to resorb. If the small fragments surrounding the rod resorb (which is common after IM rod fixation of comminuted fractures), the patient has a defect between proximal and distal fracture segments resulting in non union. Moreover, bony bridging sometimes occurs between healing bone and the IM rod itself, making rod removal difficult after healing has taken place. Occasionally the difficulty in removing the rod results in further damage to the healing bone or damage to adjacent soft tissues.
Recent developments in the art:
Several additions to the fracture treatment armamentarium have been introduced over the past few years which have attempted to address these problems. Unfortunately, each type also suffers from particular disadvantages when used in clinical practice.
1. Porous Substrates:
Recently, several authors have described using a porous substrate to provide a scaffold for bone ingrowth, e.g., Tormala et al., U.S. Pat. No. 5,084,051. These authors teach that porous, rigid ceramics can be used to serve as an anchor for growing cells. Although potentially useful to aid in cellular bridging across a fracture, their porosity precludes macromolecular restrainment. The critical feature of these devices is that they contain pores large enough to permit cells to grow into them. Since macromolecules are orders of magnitude smaller than cells, they are not restrained within the interfragmentary space by these devices. Consequently a major determinant of whether or not a fragment is resorbed, i.e., the interfragmentary concentration of growth factors and the like, is not addressed. Therefore, when devices such as those described by Tormala et al, are used, macromolecules produced by the fracture are free to exit the interfragmentary space and pass unhindered into the surrounding tissues.
Because they are designed to allow cellular ingrowth, these devices form an irreversible bond with the host tissue. Small fracture fragments are then free to resorb, causing native tissue to be replaced with prosthetic. Native tissue is always preferable to prosthetic, unless it is cancerous or is severely arthritic. Foreign material, no matter of what it is composed, dramatically increases the risk of infection by blood-borne bacteria. Orthopedic surgeons almost universally agree that the sooner all prostheses are removed, the better. Implantable prosthetics, however, remain in the body for life.
2. Bone chips or other forms of exogenous bone matrix:
Another recent development in the treatment of non-union fractures is the administration of bone chips or other forms of exogenous bone matrix. The idea is to provide a substrate for growing cells and incorporate the polymer when it becomes surrounded by growing bone. These devices, such as the implantable fixed prosthetic device (see U.S. Pat. No. 5,002,583 to Pitaru-Sandu, 1991), are composed of a rigid core surrounded by collagen that, once in the body also forms a biological bond with and integrates into host tissues. Although potentially suitable for affixing a prosthetic device to native bone, these devices are poorly suited for treatment of fractures for at least three reasons First, they are unable to restrain macromolecules produced by the fracture within the interfragmentary space. Second, the devices are rigid, making it impossible to modify them in the operating room to suit a specific need. Surgeons rarely know exactly the extent and dimensions of tissue injury until a fracture is exposed. Third, since these devices also form an irreversible bond with the host tissue, small fracture fragments resorb, causing native tissue to be replaced with prosthetic.
3. Implantable gels and injectable cements:
In the case of implantable gels or injectable cements, e.g., U.S. Pat. No. 4,642120 to Nevo-Svi, 1987, a gel is provided as an amorphous jelly containing biologically active molecules and/or living cells, or is supplied as a "quick drying bone cement". These devices are also not ideal for the treatment of comminuted fractures for several reasons, of which four deserve mention as they limit the use of these agents in clinical practice. First, because they are not supplied or applied as a sheet, the injected cement/gel/cells are free to float around the site of injury. Consequently, not only are the macromolecules critical to the healing process displaced by the gel and forced into the surrounding muscles, but over time, the injected material is also free to egress from the fracture site because there is no significant means to contain it at the site it was originally injected. Second, even if supplied as a paste, gels are unable to tightly bind small fragments together. Fragments are free to "float" around the cavity and out of the plane formed by the major fracture fragments. The failure to prevent small fragment resorption results in deformity and limb shortening if and when the fracture heals. Third, if the gel does harden within the interfragmentary space, native fracture fragments will be hindered in their ability to bridge among themselves by the intervening prosthetic. Thus, native fragments will be replaced by prosthetic as in the rigid prosthetic described above. Finally, cells and/or medications are free to diffuse from the gel in all directions, which can result in heterotopic bone formation. If a gel fragment lodges between muscle strands and forms bone around it, this could limit the use of that muscle forever.
4. Potential use of the flexible polymer coated sheet of Scharnberg et al. (U.S. Pat. No. 4,693,720)
Scharnberg et al. (U.S. Pat. No. 4,693,720) have disclosed a flexible polymer coated sheet, that is taught to be used to patch defects in the anterior abdominal wall following hernia surgery. Although this device could potentially be used to treat fractures, as claimed it does not have macromolecular restrainment means such that it can substantially restrain macromolecules produced by injured tissue within a particular space, e.g., "the interfragmentary space". Although these authors do teach of a flexible device, these authors fail to include the critical aspect of minimal-porosity. Consequently, the failure of their device to have "macromolecular restrainment means", would permit their device to allow growth factors and the like to diffuse out of the interfragmentary space and into the surrounding tissues.
5. Potential use of a non-porous graft such as that described by Kowligi et al (U.S. Pat. No. 5,152,782)
Since a major problem with healing comminuted fractures is that interfragmentary macromolecules leave the interfragmentary space, one might think that a non-porous graft could be used to restrain them and subsequently speed healing. Although this true to some extent, I have found unexpectedly that if small molecules such as water, urea, bicarbonate, and hydrogen ions are permitted to pass through the device, healing occurs much more quickly. For example, if hydrogen ions are not free to cross the device, the pH will fall within the interfragmentary space. If the pH falls, enzymes will be less active, and healing will be slower. Furthermore, if small metabolites are contained within the interfragmentary space, negative feedback loops will be activated thereby decreasing the rate of healing. Finally, the use of a non-porous graft will hinder the passage of desirable small molecules such as glucose and water into the interfragmentary space. Clearly, what is needed is a device that can restrain macromolecules but allow free passage of small molecules.
6. The Malleable Fracture Stabilization Device with Micropores for Directed Drug Delivery
The applicant of the present invention, in U.S. patent application Ser. No. 08/114,745, filed Aug. 30, 1993 and entitled "Malleable Fracture Stabilization Device with Micropores for Directed Drug Delivery" has disclosed a two layered device that contains a first layer of minimally porous material affixed to a second layer of medication-containing material. This two-layered device is capable of performing several functions simultaneously.
The Malleable Fracture Stabilization Device with Micropores for Directed Drug Delivery is a malleable fixation device that, when wrapped around or affixed to fractured tissues, holds the fragments in tight register while delivering any of a number of medications directly and specifically to the interfragmentary space. It is designed to be used with existing orthopedic devices that provide rigid fixation of major fracture fragments. With the Malleable Fracture Stabilization Device with Micropores, heterotopic bone formation is minimized, since both the exogenous (supplied by the invention) and endogenous (supplied by the native healing tissue) growth factors are directed preferentially into the fracture site. The Malleable Fracture Stabilization Device with Micropores is provided as a flexible two layered sheet that the surgeon in the operating room can staple, suture or otherwise affix to the injured site as each particular case demands.
The Malleable Fracture Stabilization Device with Micropores can deliver medicines, including growth factors, chemotheraputic agents and antibiotics, directly into the site of injury. It can also permit the free passage of small molecules such as water, small ions, glucose and urea through the device. The Malleable Fracture Stabilization Device with Micropores can approximate and stabilize tissue fragments and can be molded by the surgeon in the operating room to fit the site of injury. The flexible and semi-soft nature of this device also provides means to administer additional medicine to the site of injury at a later time. In addition, the "Malleable Fracture Stabilization Device with Micropores for Directed Drug Delivery" can be used to: 1) Deliver local chemotherapy into curettage sites or to soft tissue metastases. 2) Deliver local antibiotics to sites of infection. 3) Increase the speed of bridging between prosthetic or allograft and native tissue.
Improvements to the Malleable Fracture Stabilization Device with Micropores for Directed Drug Delivery
Although the "Malleable Fracture Stabilization Device with Micropores for Directed Drug Delivery", solves many problems not addressed by the prior art, several improvements in design can be made to make it even more desirable as a healing agent. Specifically, it would be desirable to make the device a single layer so that less foreign material be implanted into the patient. It would also be desirable to have the treating material released in a more controlled manner than mechanical efflux from pores. It would be also be advantageous to make the device as thin as possible such that it can be more easily delivered percutaneously through an endoscope, a hollow needle or a catheter. Finally, it would be desirable to be able to apply the device as a spray such that contact between the device and the tissue is maximized.
The present invention is provided as a single-layered, malleable fixation device that, when wrapped around or affixed to fractured tissues, holds the fragments in tight register while containing macromolecules produced by the injured tissue at the site of injury where they are needed most. This device, like the Malleable Fracture Stabilization Device with Micropores for Directed Drug Delivery, permits the free passage of small metabolites and water through pores in the device. When a treating material is affixed to the provided device, the device can deliver it directly and specifically to the fracture site. Medicines, when they are diffusable macromolecules, can be held to the single layer using chemical bonds such that medicines are released according to a rate constant rather than random diffusion through a matrix of pores. The device is soft enough that a needle can pierce it to administer additional medicine or to sample the fluid in the interfragmentary space without the need for reoperation.
This invention is designed to be used with existing orthopedic devices when rigid fixation of major fracture fragments is required. With this invention heterotopic bone formation is minimized, since both the endogenous and exogenous growth factors continue to be directed preferentially into the interfragmentary space. This invention is to be provided as a flexible sheet, spray or tube that the surgeon in the operating room can staple, suture or otherwise affix to the injured site as each particular case demands.
The reader will further appreciate several additional uses of the invention that can be performed with only slight modification of the basic structure of the present device. These uses include, but are not limited to the treatment of metastases, infections, metabolic disorders of bone such as osteoporosis, primary neoplasms and vascular disease. This invention can be used in conjunction with other fixation devices and implantables to augment their function and improve their healing efficacy. It is these improvements that I wish to discuss in the present application.
Objectives of the present invention:
It is a principal object of the present invention to provide a unique method of tissue stabilization and containment of interfragmentary macromolecules using a single, flexible minimally porous sheet.
It is a further object of the present invention to provide a unique method and apparatus that can perform the essential healing features of the Malleable Fracture Stabilization Device with Micropores for Directed Drug Delivery using only a single layer of minimally-porous layer to which has been affixed a treating material directly on its surface.
It is a further object of the present invention to provide a unique method and apparatus for internal treatment of fractured tissues that can be delivered via a percutaneous delivery system.
It is a further object of the present invention to provide a unique method and apparatus for internal treatment of fractured tissues that can be applied as a spray film.
It is a further object of the present invention to provide a unique method and apparatus that can be affixed to an intramedullary rod such that a treating material can be delivered from within the medullary cavity and bony bridging between the fracture and the prosthetic can be minimized allowing for easier removal of a rod, plate or screw.
It is a further object of the present invention to provide a unique method and apparatus that can be deployed via endoscope, catheter, or open surgical procedure that can serve both to preferentially direct endogenous macromolecules and release treating materials while also providing structural support to hollow viscera, solid organs, or blood vessels.
Other objects and advantages of the invention will be apparent from the following summary and detailed description of the fracture stabilization device and of the methodology applicable to its use taken together with the accompanying drawing Figures.