Patent Application
20200179573
The present invention relates to a biodegradable metal alloy for anchoring detached tissue to hard tissue, a method for making the same and a process for using the same, especially to a biodegradable metal alloy for effectively anchoring detached tissue to hard tissue, a method for making the same and a process for using the same that not only promote bone growth but also avoid metal/alloy artifacts in images.
Suture anchor technique is a way that re-attaches detached tissues to hard tissues by inserting anchors with sutures into bone tissues, and the sutures are passed through the detached tissues to move the detached tissues back to its insertion site, and then secure the detached tissues onto the position. Thus, the contact area between the tissues is increased for promoting tissue regeneration and healing.
The most commonly used materials for suture anchors are titanium alloys at first. Refer to Chinese Pat. App. Pub. No. CN203074848U, an implantable bone anchor is revealed. The bone anchor features on an implantable anchor body provided with a threaded hole on an upper part thereof and spring threads on a lower part thereof. A bone graft hole is arranged at the implantable anchor body. The implantable anchor body is threaded into the bone at the injured area by the spring threads and a cutting edge on the front end of the spring threads for fixing. Then bone fragments are filled into the bone graft hole and inserted by sutures to connect with soft tissues tightly. Thereby soft tissues of joints and bones are reconnected. Although titanium alloys provide good fixation, these non-biodegradable materials will be left in the body permanently once there is no second surgery for implant removal. The anchors may cause some adverse effects such as chronic local inflammatory reactions and the loosening or migration of anchors may cause cartilage damage. Moreover, the assessment of medical images is affected by titanium alloys. For example, the accuracy of magnetic resonance imaging (MRI) would be affected by metals, which is so called metallic artifacts. Thus, titanium alloys have been gradually replaced by polymers since metals interfere with imaging. However, as permanent implants, the mechanical properties of bioinert polymers are not as good as metal/alloy and they may cause consistent foreign body reactions in human bodies. According to many case reports, the use of bioinert polymers tends to cause several complications such as osteolysis, cyst formation, etc. As to degradable polymers, they can be absorbed over time in human bodies, but the degradable polymers have certain shortcomings. The degradable polymers have poor mechanical performance compared with metal/alloy. The degradation products of degradable polymers will ultimately lead to acidic micro-environment, which is harmful to tissue regeneration and tends to induce inflammatory reactions around the implants.
Thus, there is room for improvement and there is a need to provide a novel material for anchors used for securing detached tissue to hard tissue.
Therefore, it is a primary object of the present invention to provide a biodegradable metal alloy for anchoring detached tissue to hard tissue, a method for making the same and a process for using the same. The biodegradable metal alloy can not only secure detached soft tissue such as anterior cruciate ligament to hard tissue effectively and provide sufficient fixation strength but also avoid metal/alloy artifacts in images. The degradation products of the biodegradable metal alloy can further enhance tissue healing.
In order to achieve the above object, a biodegradable metal alloy for anchoring detached tissue to hard tissue according to the present invention includes a magnesium-zinc-zirconium (Mg—Zn—Zr) alloy and a magnesium fluoride (MgF2) coating over the Mg—Zn—Zr alloy. The Mg—Zn—Zr alloy is a magnesium alloy containing 2.5-6.0 wt % (weight percent) zinc (Zn) and 0.42-0.80 wt % zirconium (Zr). The Mg—Zn—Zr alloy is selected from the group consisting of ZK50, ZK30, ZK60, ZK51A-T5, ZK61-T5, ZK61-T6, ZK31-T5, ZK60-T5, ZK61-T5, ZK21A-F, ZK31-T5, ZK40A-T5, ZK60A-T5, ZK61, ZK50, ZK6O-F, ZK60-T4, and ZK60-T6.
In order to achieve the above object, a method for making a biodegradable metal alloy for anchoring detached tissue to hard tissue according to the present invention includes the steps of (a) selecting a magnesium-zinc-zirconium (Mg—Zn—Zr) alloy that is a magnesium alloy containing 2.5-6.0 wt % zinc (Zn) and 0.42-0.80 wt % zirconium (Zr); and (b) immersing the Mg—Zn—Zr alloy in a 42% hydrogen fluoride (HF) solution and shaking the solution with the alloy therein for 24 hours to form a magnesium fluoride (MgF2) coating over the Mg—Zn—Zr alloy.
In order to achieve the above object, a process for using a biodegradable metal alloy to anchor detached tissue to hard tissue according to the present invention includes inserting a biodegradable metal alloy into hard tissue with the free ends of sutures extending out of the hard tissue, and repairing the detached tissue to hard tissue by using Mason-Allen stitch. The biodegradable metal alloy is used for producing biodegradable anchors that secure detached tissue to hard tissue.
Thereby the biodegradable metal alloy of the present invention not only has high mechanical strength and ability to be absorbed by human bodies but also avoids metallic artifacts on interpretation of medical images (such as MRI) caused by titanium alloy, foreign-body reactions and tissue inflammation. In practice, the biodegradable metal alloy can be applied to arthroscopic surgery for repairing detached tissues such as rotator cuff tear in the shoulder.
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
The structure and the technical means adopted by the present invention to achieve the above and other objects can be best understood by referring to the following detailed description of the preferred embodiments and the accompanying drawings, wherein:
Refer to
Refer to
A method for making a biodegradable metal alloy for anchoring detached tissue to hard tissue according to the present invention includes the steps of (a) selecting a magnesium-zinc-zirconium (Mg—Zn—Zr) alloy. The Mg—Zn—Zr alloy can be a magnesium alloy containing 2.5-6.0 wt % zinc (Zn) and 0.42-0.80 wt % zirconium (Zr); and (b) immersing the Mg—Zn—Zr alloy in a 42% hydrogen fluoride (HF) solution and shaking the solution with the alloy therein for 24 hours to form a magnesium fluoride (MgF2) coating over the Mg—Zn—Zr alloy.
A process for using a biodegradable metal alloy to anchor detached tissue to hard tissue according to the present invention includes inserting a biodegradable metal alloy into hard tissue with the free ends of sutures extending out of the hard tissue, and repairing the detached tissue to hard tissue by using Mason-Allen stitch. The biodegradable metal alloy includes a magnesium-zinc-zirconium (Mg—Zn—Zr) alloy and a magnesium fluoride (MgF2) coating over the Mg—Zn—Zr alloy. Preferably, the Mg—Zn—Zr alloy is a magnesium alloy containing 2.5-6.0 wt % zinc (Zn) and 0.42-0.80 wt % zirconium (Zr). For example, the Mg—Zn—Zr alloy is a ZK50 alloy containing 5.0 wt % zinc and 0.5 wt % zirconium.
It should be noted that all mechanical properties of the alloy are decreased when the amount of zinc contained in the magnesium alloy is over a certain level such as 6.0 wt %. Moreover, microporosity occurs in the alloy and hot cracking tendency increases owing to a high amount of zinc. Once the amount of zinc contained in the magnesium alloy is below a certain level such as 2.5 wt %, the reduced corrosion resistance of the alloy caused by metal impurities such as iron, nickel etc. is unable to be improved. Thus, the amount of the zinc in the magnesium alloy is preferably ranging from 2.5% to 6.0 wt %. Moreover, the magnesium-zinc alloy with a higher zirconium content is difficult to process and cast. For example, the zirconium content is above 0.80 wt %. Yet the amount of zirconium contained in magnesium-zinc alloy is usually higher than 0.42 wt % for grain refining of zirconium. Thus, the amount of zirconium contained in magnesium-zinc alloy is preferably ranging from 0.42% to 0.80 wt %.
In a preferred embodiment, the Mg—Zn—Zr alloy is selected from ZK50, ZK30, ZK60, ZK51A-T5, ZK61-T5, ZK61-T6, ZK31-T5, ZK60-T5, ZK61-T5, ZK21A-F, ZK31-T5, ZK40A-T5, ZK60A-T5, ZK61, ZK50, ZK60-F, ZK60-T4, and ZK60-T6.
Magnesium alloy has good biocompatibility, light weight similar to bone mass and good mechanical properties. Thus, it is used as a new generation of biodegradable medical implants in recent years. According to the previous tests, magnesium alloys containing other metals have different properties such as rigidity, degree of degradation. Thus not all magnesium alloys can be applied to anchors for securing detached tissue to hard tissue. For example, magnesium alloys containing aluminum have shown to cause neurotoxicity after being implanted into human bodies. In order to develop materials suitable for fixing soft tissues and hard tissues, performance tests for these materials were carried out and analyzed.
In this embodiment, the biodegradable metal alloy used is Mg—Zn—Zr alloy, ZK50 (Zn 5.0 wt %, Zr 0.5 wt %) and the sample has a diameter of 1.2 cm and a thickness of 0.4 cm. The ZK50 alloy was immersed in a 42% hydrogen fluoride (HF) solution and the solution with the alloy sample therein was shaken for 24 hours to form a magnesium fluoride (MgF2) coating for increasing the corrosion resistance. Refer to
Electrochemical tests were performed for corrosion resistance analysis. The corrosion current density was determined by the potentiodynamic polarization curve. More specifically, potentiodynamic polarization tests were conducted at the scan rate of 0.001 V/s and the scan range of −2 V to −1 V. The test temperature was controlled at room temperature (about 25° C.) and the solution used was revised simulated body fluid (r-SBF). The electrochemical tests were performed on the surface of the samples to estimate the corrosion property of them. After scanning, the data obtained was plotted to form
Hydrogen gas is released during corrosion of magnesium alloy. Thus the larger volume the hydrogen gas released represents the lower corrosion resistance of the alloy. The test results are shown in
Testing for cytotoxicity is an important step toward ensuring the material's biocompatibility. ZK50 alloy and MgF2—ZK50 alloy were immersed into cell culture medium respectively and placed in an incubator (5% CO2 & 37° C.) for 24 hours. Then extraction was carried out to get extracted medium of ZK50 alloy and extracted medium of MgF2—ZK50 alloy. Human osteoblast-like MG63 cells were cultured in the extracted medium of ZK50 alloy, the extracted medium of MgF2—ZK50 alloy, and culture medium only (as the control group), respectively. The cell viability in all groups from day 1 to day 7 was tested and the results are shown in
In order to learn adhesion of the osteoblasts on surface of various materials or implants, the cell adhesion morphology was analyzed through observation of scanning electron microscope (SEM). Human osteoblast-like MG63 cells derived from an osteosarcoma were seeded on both the ZK50 surface and the MgF2—ZK50 surface for 4 hours and 24 hours, respectively and then fixed and dehydrated in turn. The test results are shown in
Refer to
In this embodiment, the biodegradable metal alloy used is Mg—Zn—Zr alloy, ZK50 alloy (Zn 5.0 wt %, Zr 0.5 wt %). The metal alloy was processed by the computer numerical control (CNC) machine to get magnesium alloy anchors with proper size for being applied to New Zealand White rabbits' shoulders. Then the ZK50 anchors were immersed in a 42% hydrogen fluoride (HF) solution and the solution with the alloy anchors therein was shaken for 24 hours to form a magnesium fluoride (MgF2) coating on the anchor for increasing the corrosion resistance. The anchor produced is shown in
In animal tests, magnesium alloy anchors made of biodegradable metal alloy MgF2—ZK50 and titanium anchors (Ti6Al4V) with sutures were implanted into animals first and then harvested with the hard tissue surrounding the anchor as a whole to perform pullout tests.
Pullout tests were conducted on euthanized rabbits' shoulders (n=5) to learn initial fixation of torn tendon provided by different anchors. Two anchors including Ti6Al4V anchor and MgF2-coated ZK50 (MgF2—ZK50) anchor were implanted into the left limb and the right limb, respectively of the rabbit and each anchor was provided with sutures (FiberWires). After the anchor being implanted into the humeral head of rabbit's shoulder, only the humerus with the suture anchor was harvested from the rabbit to perform pullout test for reducing the influence of the tendons with different properties. As shown in
Refer to
Refer to
During animal testing, the recovery of rotator cuff repair in two groups implanted with magnesium anchor (MgF2—ZK50) made of biodegradable metal alloy and titanium anchor (Ti6Al4V) made of conventional titanium alloy, respectively after surgery was compared.
The tendon and bone tissues containing the anchor are harvested 1 month after surgery and 3 months after surgery, respectively, and the recovery of the tissues was observed. Refer to
Refer to
As shown in
Compared with techniques available now, the present invention has the following advantages:
Additional advantages and modifications will readily occur to those skilled in the art. Therefore, the invention in its broader aspects is not limited to the specific details, and representative devices shown and described herein. Accordingly, various modifications may be made without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalent.
