Absorbable polyglycolide devices in trauma and bone surgery

Biomoteriols 18 (1997) 3-9 0 1996 Elsevier Science Limited

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REVIEW Absorbable polyglycolide devices in trauma and bone surgery Nureddin Ashammakhi and Pentti Rokkanen Department of Orthopaedics and Traumatology, Helsinki University Central Hospital, Topeliuksenkatu FIN-00260 Helsinki, Fin/and

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Poly(glycolic acid) or polyglycolide (PGA) is a polymer of glycolic acid. Glycolic acid is produced during normal body metabolism and is known as hydroxyacetic acid. Strong implants can be manufactured from this polymer with a self-reinforcing (SR) technique and used in the treatment of fractures and osteotomies. Since 1984, SR-PGA implants have been used routinely in our hospital for internal fixation of bone fractures. These implants were studied extensively in experimental animals and proved biocompatible. In 1.7% of human cases, sinus formation may develop after the use of these implants, which does not disturb healing. Use of these absorbable implants is justified as it obviates the need for a second operation for implant removal and avoids the risks associated with biostable implants. 0 1996 Elsevier Science Limited Keywords:

Review,

self-reinforced

polyglycolide,

absorbable,

bone, fixation,

biocompatibility

Received 22 February 1996; accepted 12 June 1996

High-molecular-weight PGA is a hard, tough, crystalline polymer melting at about 224-228X with a glass transition temperature (T,) of 36°C. The polymer can be spun to form fibres when its average molecular weight is 20 000 to 145 OOOX7.The strength properties of PGA are increased when spun into the fibre form, because of the preferred higher molecular orientation of the polymerss14. Films and different objects can be made of PGA*2,1s. Glycolide, the cyclic diamer condensation product, is formed by dehydrating hydroxyacetic acid (glycolic acid). PGA or polyglycolide can be synthesized from glycolide under the influence of an inorganic metal salt catalyst at a low concentration by a ring-opening polymerizationl’. The molecular weight of the final polymer is controlled by the temperature, time, concentration of catalyst and concentration of the chain-length det&%nining agent. Once the polymer is of sufficiently high molecular weight, it is extruded into filaments of the desired size, which are then converted into multifilament yarns. The yarns are combined and braided to give the final fibre material.

Glycolic acid is produced during normal body metabolism and is known as hydroxyacetic acid’. The polymer of glycolic acid is known as poly(glycolic acid) or polyglycolide (PGA). PGA is the lowest member of a class of hydroxy fatty acids of which lactic acid is the best known’. PGA of low molecular weight was first synthesized and described about one hundred years ago3. Higher molecular weight PGA was synthesized by a ring-opening polymerization method4 and later PGA with thermoplastic properties was synthesized’. PGA sutures (Dexon”) have been commercially available since 19705. Strong selfreinforced oly 1 colide (SR-PGA) implants were gy h.ave been in clinical use since developed J - and 1984” ‘. In this paper we review the up-to-date information about SR-PGA devices.

POLY(GLYCOLIC

ACID)

Chemistry and synthesis Poly(a-hydroxy acidls constitute a particular class of polymers whose repeating units, -(O-CO-CHR)-,, are derived fkom a-hydroxy acids, HO-CHR-COOH. This class has been under research for the development of osteosynthesis devices since the 1960s”-‘6. Implants made of PGA or poly( lactic acid) (PLA) are the strongest that could be developed from this class’*.

Fabrication The first poly(a-hydroxy acid) that was developed for sutures was made from PGA. It was commercially available in 1970 as Dexon@ sutures5. Macroscopic implants such as rods, plates or screws can be manufactured in different ways such as with

Correspondence to Profi~ssor P. Rokkanen. 3

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compression moulding and injection moulding, and moderately strong implants can be produced14. Ultra-high strength (bending strength up to 405MPa) SR-PGA implants have been developed by sintering mechanical deformation (drawing) and by techniques6.7,8p1g.

Self-reinforcing Self-reinforcing implies the formation of a composite structure made of a certain polymeric material comprised of oriented reinforcing units, like fibrils or fibres, and binding matrix, both having the same chemical structure6. Tormala et ~1.~ first introduced the sintering self-reinforcing technique, by which macroscopic implants can be built up from strong fibrous polymer units by glueing them together. This has improved the strength properties of partially crystalline PGA implants, and strong devices were produced”. The more advanced self-reinforcing technique, partial fibrillation by orientational drawing, has further strengthened the SR implantslg. The oriented fibres strengthen the implants significantly’.

Degradation Cutright et ~1.” studied the degradation rates of PGA cylindrical pellets implanted in 225 rats’ femora. Implants were replaced by fibrous, osseous and marrow tissue. Although Miller et ~1.~~ found no difference in the rate of degradation in the soft tissues or bone of rats, Vasenius et ~1.‘~ found that degradation was slightly faster in the medullary cavity than in the subcutaneous tissue of rabbits. The degradation of PGA cylinders in sheep femora occurred in 4-5 months, with replacement by bonez4. Vert et ~1.‘~ found that PGA cylinders implanted in tibia1 cortices of rats were not degraded within 9 months. Vainionpla” found that PGA implants degrade to a great extent in cancellous bone and partly in cortical bone of rabbits within 12 weeks, with degradation that starts from the periphery inwards, the implants subsequently being replaced by bone. The degradation begins with random hydrolysis in an aqueous environment. In viva, however, enzymes are thought to enhance the initial degradation’“. The hydrolytic degradation in viva may take place via nonspecific esterases and carboxyl peptidases that produce glycolic acid monomers which are converted enzymatically into glycine, which can be used in protein synthesis, or into pyruvate that enters the tricarboxylic acid (TCA) cycle2792a yielding energy, CO2 and water. Glycolic acid is partially excreted in urine 17,27,28 . Hence, material eventually the disappears*. Hydrolysis is affected by the initial molecular weight, surface area/weight ratio, porosity and monomer concentrationzg, geometric isomerism and conformation and crystallinity’4. Increased pH accelerates PGA degradation3’. Macrophages were demonstrated around SR-PGA screws in cancellous bone of rabbits and were thought to be responsible for ultimate digestion and clearing of the decomposing polymeric materia13*. SR-PGA screws have vanished in cancellous bone of rabbits at 250 d3’ to 48 weeks3’. Biomaterials

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Biocompatibility At 7 d a layer of fibroblasts was noticed around SR-PGA screws implanted in the cancellous bone of rabbits3’. In this study the tissue-implant interface between SRPGA screws and cancellous bone was investigated and no contraindication against clinical application of PGA implants was found. No allergic reactions were recorded after the use of SR-PGA pins for the fixation of extra-articular fractures in the hand during the follow-up period of 6 months33. Vainionpaa” found that PGA rods were biocompatible with bone tissue of rabbits and did not cause any sign of inflammation or foreign-body reaction. Miller et a1.22 have studied 14C-labelled polymers in rats and found that PGA was metabolized entirely without any vital organ accumulation. SR-PGA screws studied in cancellous femoral bone of rabbits showed a regular front of phagocytes around the implants34, being highest at 12 weeks, with giant cells adhering to the implant surface at an earlier stage31 and defined by Bostman et c11.~’ in another study to be at 80 d. In the later study PGA screws were also used to fix cancellous femoral bone osteotomies in rabbits. Antikainen et ~1.~~ have used interpositioning SRPGA membranes for the treatment of craniosynostosis. The membrane fragmented into pieces and became surrounded by giant foreign-body cells. A thin layer of new bone and suture-like structure subsequently formed. The membrane was considered biocompatible. SR-PGA rods implanted subperichondrially to replace resected costal cartilage of rabbits have enhanced surrounding cartilage and bone formation36-38. Foreign-body reaction was also recorded and has not disturbed the chondrogenic potential of the perichondrium. New cartilage formation was also seen with SR-PGA flates implanted subperichondrially in rabbits’ ears3 . Chondrocytes were grown successfully, both in vitro and in viva, on SR-PGA scaffolds and the possibility of application in reconstructive surgery was raised4’. Ashammakhi and co-workers41-43 have implanted SR-PGA membranes around femoral bone of rats and rabbits and found that these membranes are biocompatible with osseous tissue and applicable in the treatment of bone defects and osteotomy augmentation. B6stman44 postulated that tibiofibular diastasis after fixation of fractures of the lateral malleolus and bimalleolar fractures (in 3.8%) was due to the osteogenic potential of the PGA rod polymeric material. B&man et ~1.~~ also noticed new bone formation around SR-PGA screws used for fixation of femoral cancellous bone osteotomies in rabbits. In an in vitro study, osteoblast-like cell proliferation, adhesion and attachment were tested on biodegradable polymers and found to be highest on PGAIPLA compared with other copolymers4 . SR-PGA implants used for internal fixation were associated with local minimal foreign-body tissue inflammatory reaction31. Sterile fluid accumulation and sinus formation usually occurred after 6-12 weeks47 or 1248 to 16 weeks postoperatively4’ in 8% of patient?‘. Sterile sinus discharge was recorded in 4% of cases of corrective Austin-type bunionectomies (osteotomies) fixed with SR-PGA pins51. Incidence was higher with the first-generation SR-PGA screws with

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an aromatic quinone dye48. Immunological studies revealed non-specific activation lymphocytic secondary to inflammatory mononuclear cell migration and adhesion5’. In 336 patients, operated on in 1992 using SR-PGA fixation devices, fluid accumulation occurred in only 0.6% and sinus formation in 1.7%~‘. Moderate transient foreign-body reaction to SR-PGA screws in rabbits’ ca.ncellous bone was seen histologically3’. Moderate transient foreign-body reaction to SR-PGA membranes implanted in the back muscles of rabbits was also nNoted53. The reaction to SR-PGA screws used for fixation of malleolar fractures in humans was found to be non-specific48. Although it is generally accepted that this reaction does not interfere with fracture healing, in two cases it was reported that the reaction to SR-PGA pins has interfered with the healing of intra-articular radial fractures54. When K-wires were compared to PGA rods in the treatment of distal radial fractures (Frykman types I, II, V and VI) in 15 hum,an cases, PGA was associated with more foreign-body reactions at 3-6 months55, where the technique could be a causative factor. Union of displaced malleolar fractures treated with SR-PGA screws48 or with SR-PGA rodss6 was not affected by the reactions which arose. Microscopic examination of the fluid accumulations that occurred in 18 of 286 patients revealed a nonspecific foreign-body reaction, composed mainly of neutrophilic leucocytes and polymorphonulear foreign-body giant cells phagocytosing the polymer debri?“. Only six of these patients with malleolar fractures fixed with PGA rods had intense reaction that needed repeated surgical treatment and admission to hospita15”. In studies on rabbits, SR-PGA screws were used to fix cancellous femoral bone osteotomies; osteolytic of the implant cavity45 and proximal expansion transient osteolysis5” were seen. In X-rays of human malleolar fractures that were fixed with SR-PGA rods, an increase in the diameter of the implant channel in the bone56 and in the line of fracture57, dispersion of PGA particles and migration of implant particles from the implant cavity to cancellous marrow spaces, 2.8mm away, were also recorded34. Osmotic pressure that developed within the implant cavity during the depolymerization process was thought to be the cause56. in a case of intra-articular Synovial reaction osteochondral fixation with SR-PGA rods was reported to be probably related to the dose of implant, delay of operation or sensitization to PGA used previously5’ or possibly due to the operative technique. Hirvensalo et d.5g reported sterile synovitis in one out of eight cases following transarticular fixation of humeral capitellum fractures (type I) with SR-PGA pins. The effusion was drained and subsided within 3 weeks without further intervention. No failure of fixation occurred.

DEVICES AND APPLICATIONS PGA implants such atspins, plates and intramedullary rods for internal fixation were described by Schmitt and Polistina”. Christel et ~1.‘~ concluded that PGA cylinders degrade rapidly and are inadequate for osteosynthesis. Small plates of PLA/PGA reinforced

with PGA fibres were used in mandibular and calvarial bone repairz5. PGA rods were used, along with PGA threads, in the fixation of distal femoral osteotomies in rabbit$‘*“‘. From 1984, these rods have been used in the fixative of Weber A and B malleolar fractures4g*50362.63, However, these implants were difficult to form into screws. Tormall et a1.“4 and Vainionpaa et a1.65 developed stronger, self-reinforced PGA composites, manufactured into rods, which were applied for internal fixation of fractures and osteotomies. SR-PGA rods have been used for the fixation of osteochondritis dissecans or osteochondral fragments in joints with good clinical results”“. The developed SR-PGA rods had a high initial strength of 250 MPa65. Solid union of femoral shaft osteotomies in five dogs occurred with the use of intramedullary SR-PGA rods (4.7 mm)67. SR-PGA pins of diameter lmm have been used successfully in the fixation of distal femoral epiphyseal fractures in growing rabbits (5 weeks old) with no growth disturbance68. In the treatment of distal humeral physeal fractures in 19 children, MZkela et al.6g used 1.5mm SR-PGA pins successfully. Svensson et al.54 used 1.5-2.0mm pins in the fixation of 50 cases of transphyseal and osteochondral fractures that were followed up for at least 1 year and showed healing in all but two cases with non-union. Hope et aL7’ reported better results with the use of SR-PGA pins than Kirschner wires in the fixation of elbow fractures in children. A case was reported where an intra-articular fracture of the talus was fixed with a 2.0 mm SR-PGA pin applied arthroscopically71. Normal healing occurred without complications and the procedure was advocated for further use. Nowadays, 1.5-2.0 mm diameter pins are in clinical use in paediatric orthopaedics with satisfactory results48. SR-PGA pins were used successfully to fix radial head fractures55372 and chevron osteotomy73-75. Gerbert5* and Kumta et a1.33 used PGA pins (1.5mm) successfully in the fixation of car al and phalangeal 7r fractures in 15 patients. Yen et al. used SR-PGA pins (2mm) successfully in the fixation of osteotomies for the correction of hallux valgus in 10 patients. In only one case did subluxation occur. SR-PGA pins have also been used for the transarticular fixation of humeral capitellum fractures with good function regained77. SR-PGA screws were also developed and studied for fixation of femoral osteotomies in rabbits31s32*78 and in humans since 198777Z79-82. They were used mainly for severe malleolar fractures and also for patellar, tibia1 condylar, humeral neck, olecranon and femoral head fractures81’82, acromio-calvicular luxation and radial fractures82. Solid fusion was achieved in 617 of arthrodeses (talocrural) of the ankle fixed with SR-PGA screwsa3. Ylinen et a1.84 used PGA splint (mesh) as a container of hydroxyapatite (HA) particles in the mandible of 20 sheep and found that the splint effectively confines the HA particles on the alveolar ridge. SR-PGA Antikainen et a1.35 used interpositioning membranes for the treatment of craniosynostosis to prevent early postoperative reunion in 14 newborn rabbits. The membrane seemed to prevent the development of skull deformity during growth when compared to early suturectomy alone. Biomaterials

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SR-PGA membranes (0.15 mm thick) were used in 20 patients for reconstruction of the orbital floor, and also for maxillofacial repairs5 and in another 12 patients in another centres6. The membranes were described as excellent materials for tissue support and guidance, valuable in covering small bone defects as in the orbital floor, frontal sinus walls and alveolar walls. We have studied SR-PGA membranes placed over bone defects in rabbits’ femoral metaphyses and observed good effect on healing compared with noncovered defectsa7. When we have used these membranes on metaphyseal osteotomies in rabbits, they had no adverse effects on osteotomy healing, suggesting their possible use to augment bone hagments in the case of comminuted fracturess8.

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Advantages For bone repair and regeneration, different kinds of biomaterials can be used, including the non-absorbable ones. However, the use of an absorbable implant obviates the need for a second operation for implant removal. Most reoperations are technically difficult and are complicated with more tissue damage. Such operations can consume more time and facilities*’ and add to expenses. Use of absorbable implants eliminates the risks associated with the presence of a foreign material permanently in the body, such as tumorogenic potentialgo. Stress concentration at rigid implants was associated with either implant or bone fractures” as a result of bone resorption leading to weakening of the bonegl,“. Effects of infection may be magnified in the presence of such implantsg3. Products from corrosion of metals can accumulate within the fibrous tissue capsule or at the capsule-implant interfacegl. It is recommended by the AO/ASIF school that metallic fracture fixation implants should be removedg43g5. Absorbable implants can be also utilized as drugreleasing systemsg6-gg. One can use them to release growth factors, for example, to stimulate fibroblast After proliferation1oo or other tissue regeneration. successful guided tissue regeneration using absorbable materials, there is, ideally, no difference between the new tissue and the original host tissue. This method comes closest to autografting8g’*01.

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CONCLUSIONS PGA is gaining wider use in the management and include especially fixation of bone. Indications cancellous bone fractures and osteotomies. PGA is biocompatible with osseous tissue and is eliminated through natural metabolic pathways. It may give rise to fluid accumulation and sinus formation in a few cases. The benefits gained by the patient and the hospital make the use of these implants justified.

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