Milagro Advance (Beta-Tricalcium Phosphate, Polylactide Co-Glycolide Biocomposite) Interference Screw for Anterior Cruciate Ligament Reconstruction

Introduction

Biodegradable interference fixation screws were introduced to the market in the mid-1990s. The appeal of these devices included improved postoperative imaging compared with metallic devices, reduced graft laceration concerns, decreased stress shielding by the gradual transfer of load during the degradation process, less chance of divergence during insertion, and easier revision surgery ( Fig. 72.1 ). These biodegradable materials provide sufficient load-to-failure strength and allow an aggressive rehabilitation program if one is desired. Offsetting these benefits are concerns about screw breakage during insertion, the length of time required for reabsorption, what is left after complete screw reabsorption, and the potential for marked inflammatory reactions leading to lytic changes, intraosseous fluid collection, and cyst formation.

The first biodegradable interference screws were made from poly- L -lactide (PLLA). PLLA screws provided effective graft fixation. The slow degradation of PLLA required many years to achieve complete reabsorption. Consequently few adverse inflammatory reactions were reported. No differences in outcomes have been observed when biodegradable screws are compared with metal screws. Later interference screws made of dextro and levo stereoisomers of lactide and copolymers combining PLLA with other polymers such as polyglycolic acid (PGA) were introduced. As a polymer becomes more amorphous, its speed of degradation increases. The degradation of poly- D , L -lactide (PDLLA) is significantly faster than that seen in pure PLLA. Increasing the percentage of the dextro monomer relative to the levo monomer changes the physical properties and increases the degradation speed.

The most recent advance in biodegradable implants came with the introduction of biocomposites. A biocomposite combines a standard biodegradable polymer (PLLA) with a bioceramic. The most common bioceramic used for orthopaedic applications is beta-tricalcium phosphate (β-TCP). Other bioceramics include hydroxyapatite, calcium sulfate, and calcium carbonate. Combining PLLA with β-TCP creates a structure possessing properties of both materials. The compressive strength and stiffness of β-TCP is very high, and when blended with PLLA imparts these characteristics to the biocomposite. PLLA/β-TCP degrades more rapidly than pure PLLA and has been shown to result in osteoconductive ingrowth of bone into the location of the implant.

The Milagro Advance screw (DePuy Mitek, Raynham, Massachusetts) is the latest version of this biocomposite interference screw and is made of 30% β-TCP bioceramic and 70% PLLA/PGA copolymer. Versions of the interference screw have been in clinical use for several years and demonstrate osteoconductive behavior.

Biomechanical and Biochemical Data

There are five stages of implant degradation: hydration, depolymerization, loss of mass integrity, absorption, and elimination. How rapidly an implant degrades is influenced by the polymer the implant is made of, the degree of crystallization (or the amorphous nature) of that polymer, the initial polymer mass (implant size), surface coverings, whether the polymer is self-reinforced, implant processing (machining or injection molding), the sterilization technique, and the environment in which the implant is stored. In addition, the degradation differs considerably based on the hydrophilic or hydrophobic nature of the different polymers.

Degradation starts at the amorphous phase of the implant and leads to fragmentation of the material to smaller parts, which are then phagocytosed primarily by macrophages and polymorphonuclear leukocytes. The lactic acid component is broken down by hydrolysis. The resultant monomers enter the Krebs cycle and are further dissimilated into carbon dioxide and water. In addition to hydrolytic chain scission, glycolic acid monomers are degraded by the enzymatic activity of esterases and carboxypeptidases.

A biodegradable material does not degrade without inflammation. The longer the degradation, the less visible the inflammatory response will be. Usually there is a mild, nonspecific tissue response with fibroblast activation and the invasion of macrophages, multinucleated foreign-body giant cells, and polymorphonuclear leukocytes during the final stages of degradation. Because PGA has a more rapid degradation, foreign-body reactions of varying degrees of severity have been reported with this polymer. These range from mild osteolytic changes to intense granulomatous inflammatory soft-tissue lesions necessitating surgical intervention.

Biomechanical and Biochemical Data

There are five stages of implant degradation: hydration, depolymerization, loss of mass integrity, absorption, and elimination. How rapidly an implant degrades is influenced by the polymer the implant is made of, the degree of crystallization (or the amorphous nature) of that polymer, the initial polymer mass (implant size), surface coverings, whether the polymer is self-reinforced, implant processing (machining or injection molding), the sterilization technique, and the environment in which the implant is stored. In addition, the degradation differs considerably based on the hydrophilic or hydrophobic nature of the different polymers.

Degradation starts at the amorphous phase of the implant and leads to fragmentation of the material to smaller parts, which are then phagocytosed primarily by macrophages and polymorphonuclear leukocytes. The lactic acid component is broken down by hydrolysis. The resultant monomers enter the Krebs cycle and are further dissimilated into carbon dioxide and water. In addition to hydrolytic chain scission, glycolic acid monomers are degraded by the enzymatic activity of esterases and carboxypeptidases.

A biodegradable material does not degrade without inflammation. The longer the degradation, the less visible the inflammatory response will be. Usually there is a mild, nonspecific tissue response with fibroblast activation and the invasion of macrophages, multinucleated foreign-body giant cells, and polymorphonuclear leukocytes during the final stages of degradation. Because PGA has a more rapid degradation, foreign-body reactions of varying degrees of severity have been reported with this polymer. These range from mild osteolytic changes to intense granulomatous inflammatory soft-tissue lesions necessitating surgical intervention.

Basic Science of Beta-Tricalcium Phosphate Copolymers

Bone replacement technology has been in development for many years. Calcium phosphate ceramic materials like β-TCP have been studied as potential bone replacement materials for decades. The calcium phosphates are used as bone void fillers, autograft extenders, and coatings for various implants, including joint replacements. They are also used in products where reabsorption of the device and replacement with native bone are desired, including different orthopaedic and maxillofacial applications.

Different biocomposite interference screws have been introduced to the market. They have different speeds of degradation. If the speed is too great, problems can develop. One screw, the Calaxo interference screw (Smith & Nephew Endoscopy, Andover, Massachusetts), was made from an amorphous polymer consisting of 65% poly ( D , L -lactic co-glycolic acid) and 35% calcium carbonate. Within the 65% portion (which is the copolymer of lactide and glycolide), 85% was lactide and 15% glycolide. The percentage of levo and dextro monomers in the PDLA component was 50% D and 50% L . This composition resulted in too-rapid degradation, resulting in clinically significant adverse events including screw swelling and sterile pretibial abscesses. Because of these issues, the Calaxo screw was withdrawn from the marketplace.

There are three terms that are important in understanding the effects of biocomposite materials: osteoconductivity is the ability to serve as an interactive template or scaffold for forming new bone; osteoinductivity is the ability to induce the creation of a new bone; and osteogenesis is the actual production of bone, such as occurs with an iliac crest autograft. Many of the current biocomposite materials have been shown to be osteoconductive, but none are osteoinductive or osteogenic.

As previously mentioned, biocomposites are a blend of biodegradable polymer and bioceramic. How evenly dispersed or homogenous the two composite components are and the size of the bioceramic are other important properties. Biocryl Rapide is the material name for the biocomposite of the Milagro screw. In this material the β-TCP is highly dispersed within the copolymer by a proprietary manufacturing process known as microparticle dispersion. The addition of polyglycolide to polylactide creates a copolymer that biodegrades more rapidly and is completely absorbed in 3 years. This biocomposite consists of 30% osteoconductive β-TCP and 70% polylactide co-glycolide (PLGA).

Osteoconductivity can be quantified using the Barber-Dockery scale. In this classification system, ossification ranges from 1 to 4. Type 1 ossification demonstrates little or no ossification and has a density measured in Hounsfield units consistent with that of soft tissue. A type 2 score is associated with some ossification, which is discontinuous or with a wide lucent rim. Type 3 demonstrates ossification filling most of the screw site with a thin lucent rim. Type 4 has good, complete ossification with a vague tract border (no sclerotic rim), suggesting good incorporation with the adjacent cancellous bone. Types 3 and 4 are deemed to be desirable results.

Using computed tomography (CT) scans, different biocomposite interference screws demonstrate a range of osteoconductive effects. As a baseline, pure PLLA interference screws used for anterior cruciate ligament (ACL) reconstruction were CT scanned 7 years after implantation in a bone–patellar tendon–bone autograft model. Tissue densities measured in Hounsfield units were obtained at various sites, including the tibial screw, tibial bone plug, tibial cancellous bone, femoral screw site, femoral bone plug, femoral cancellous bone, and adjacent muscle. In all cases, complete degradation of the PLLA screw with no residual material left at the site was confirmed. All bone plugs completely healed to the tunnel wall. The PLLA material was not replaced by trabecular or cortical bone. The ossification quality score of these cases was a 1.

A biocomposite biodegradable interference screw composed of 75% PLLA and 25% β-TCP was studied next, also in a series of arthroscopic patellar tendon autograft ACL reconstructions. At an average of 50 months after surgery, CT scans showed the bone plugs healed to the adjacent tunnel wall with no PLLA/β-TCP material remaining. Osteoconductivity was present in 75% of the tunnels and complete in 10%. The ossification quality scores were types 3 and 4 at the tibial and femoral screw sites in 33%.

The Milagro Advance interference screw is made from Biocryl Rapide, which has 30% β-TCP by weight. This is 5% more β-TCP than the other biocomposite screw, and the Milagro Advance PLLA is blended with PGA at a ratio of 1 to 5.66, making it more amorphous with a faster degradation while adding more calcium ions to the structure. CT scans obtained at an average of 38 months after surgery demonstrated that osteoconductivity was present in 81% of the tunnels and complete in 19%. The ossification quality score was type 3 and 4 at the tibial and femoral screw sites in 50% of cases, which contrasts sharply with the 33% present in the 25% β-TCP/75% PLLA screw.

Clinical Information

The Milagro Advance screw can be used for either femoral or tibial fixation for soft tissue for bone–tendon–bone autografts or allografts ( Figs. 72.2 and 72.3 ). It is provided in various diameters from 7 to 12 mm and 23-mm, 30-mm, and 35-mm lengths. As previously mentioned, the screw is composed of a biocomposite material called Biocryl Rapide, which consists of 30% osteoconductive β-TCP and 70% poly- L -lactide co-glycolide. The PLA/PGA copolymer is composed of 15% PGA and 85% PLA. This ratio of PGA to PLA, chosen following animal studies, allows a faster yet controlled absorption. The threads are spaced so that only six revolutions are required to fully insert the screw. This is half as many turns as are required for other interference screws. In addition, the new distal-tip, geometry requires significantly less axial load than other screws to engage the threads.