Studies of polyurethane urea bands for ACL reconstruction ELISABETH LILJENSTEN*t, KATRIN GISSELF HANS BERTILSSON, PER FLODIN AUT, BENGT EDBERG.. Research and Development Department, Artimplent {institute of Anatomy and Cel Biology, Géteborg Una, Gomenbura. Sweden E-mail: elisabeth.lijensten@artimplant.se ma tg ANDERS NILSSON Department of Hand Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden ANDERS LINDAHL Institute of Laboratory Medicine, Gothenburg, Sweden LARS PETERSON Gothenburg Medical Center, Gothenburg, Sweden SSeS cpa che The present report describes the mechanical tests, Section for Clinical Chemistry and Transfusion, \liviana Guite poly(urethane urea) (PUR) intended for clinical use reconstruction. In the mechanical tests, mater rabbits and minipigs. The first clear histolo detected after 24 months. In conclusion, the evaluated mechani reconstructions, © 2002 Kluwer Academic Publishers in vitro and in vivo studies of a in anterior cruciate ligament (ACL) ene 8 observed after repeated cyclic loading. Testings for mutagenicity an seve"? fatigue wa: found negative. Three in vivo studies were pertorme rabbits were operated upon in (1) an intraarticular imp the soft tissue response to woven bands and fiber be, study, examining the function of the PUUR ACL ro I. In a third study, PUUR ACL replacement in mien ‘growth of connective tissue in close contact with the is Nd delayed contact hypersensitivity were “I in rabbits and minipigs. Altogether 35, lantation study, performed to evaluate indies of PUUR and (2) a rabbit ACL Placernent and the tissue response to the H 1s was evaluated. Taken together, UR fibers was detected both in sical signs oF degradation of the polymer was | properties IR band correspond to those of the mature, human ACL. Furthermore, both from a fens o er an correspond to tho: view, the PUUR woven band show interesting prop @ histological and functional point of erties for future clinical ACL Sears rear e eve ceeaEoRereeeecreuaacaee ee aia amdaU Sena ainda, CORD SnAaISE SEA Introduction ‘The anterior cruciate ligament (ACL) isthe primary and ‘most important stabilizer of the knee [1]. Rupture ofthe ACL. are the most common serious ligament injuries, and with conservative treatment, the knee joint will progress into osteoarthritis in over 50% of the eases (2-5). After surgical weatment, a numberof patients have unstisfac- tory long-term outcome with pain, loss of motion, Progressive instability, graft failure and development of osteoarthritis (6-10}. Presently, the most used autografts for ACL. recon- structions are the central third of the patella tendon and adjacent bone, multiple loops of the semitendinosus _gacis tendons or the quadriceps tendons (11-13). The ‘decreased stability overtime, the donor-ste morbidity in ‘eppcoximately 5-30% of the patients und reoperation rates of 30% [13-17], have resulted in a search for an “Avtar vom concn se ae ARI AB Hal Bg (857-4590 © 2002 Kluwer Academic Publishers ACL utite duping bot te stctie and uaction ofthe human ACL. "Steric non-degradable ligament bands, of for {zimPle, polyteratuoroethylene, polythylenetereptha- HS(1. 47-21), polypropylene, polyethylene and carbon fives (16,22) ‘were introduced” three decades ago over, they were abandoned after a short period due 1 adequate ‘mechanical properties. "Ong theft synthetic males used for degrad- Ae device. was polydinanone (PDS), used a6 an igmenation to stabilize the autograft. However, the stiffoess. of the PDS led to stress shielding phenomena (23). Currently no salstactory ACL devie re vale fr clinical practice. The need of a degradable ACL subsite, for prosbeue or aigmentition prposes, based on! a biocompatible polymer with degradation “MES exceeding those of PDS to allow ingrowth and ‘$6421 32 Vian Fdlnds, Swen, 351adaptation of the autogenous tissue formed, and with mechanical properties similar tothe human ACL isa high clinical priority. Further, the synthetic ACL device must be able to recapture its original length after loading in a similar manner as the human ACL does (24). The polyurethane class of synthetic polymers has proven to be well tolerated by the human body when used as for ‘example, catheters (25}, lead insulation for pacemakers [26), vascular prostheses [27], artificial hearts (28,29) and may constitute a suitable material for ACL prosthesis. ‘The aim of the present study was to evaluate new degradable polyurethane ures (PUUR) bers [30] intended for ACL reconstruction. Initial in vitro in vivo and mechanical data are presented. Materials and methods Chemical composition and fiber spinning “The poly(urethane urea) was synthesized by a two step method deseribed earlier (31,32). In the first step polyeaprotactone diol, (PCL) (M, = 330g/mol) (Aldrich, Germany) was end-capped with 4,4-diphenyl- ‘methane diisocyanate (MDD) (Bayer AB, Sweden) (NCO: OH =2: 1). In the second step the prepolymer was dissolved in N.N-dimethylformamide (DMF) (Fluka, Switzerland) to a concentration of 15-20% by weight followed by chain extension with |.3-diamino- propane (Merck AG, Germany). PUR fibers (Fig. (a), () were prepared by wet spinning (32). The PUUR solution vas extruded through a spinneret (60 holes 80m in diameter into a precipitation bath of water. Ina second bath the fibers were drawn 400-600% before they were collected on final take up unit Band manufacturing ‘The wet spun multifilament fiber was converted by doubling and slight twisting to a coarse yarn, which was used as warp threads. The bands were woven with low eft tension in plain weave to utilize the yarn strength as much as possible combined with good stability. The PUUR bands were sterilized using ethylene oxide. The 352 PUUR bunds used in the rabbit ACL study had a thickness of 20mm and a width of 40mm. The corresponding dimensions of the PUUR bands used in the minipig ACL study was 4.0mm and 6.0mm. Tensile testing ‘Three woven bands (rabbit ACL band) were tested in a wet state after equilibration with water at 20°C in a tensile tester (Alwetion tensile tester, Stockholm, Sweden), ‘The constant rate of extension was 900mm min’. The ultimate load (N) and the ultimate clongation (mm) were determined. Cyclic tests In order to study the elastic behavior during repeated clongation, 50 elongation cycles between the limits 10 30mm elongation were performed at | Hizon the 100 mm long bands, i’ a wet sate after saturation in water at 20°C, using a tensile tester (UT 350, SDL International, England). In vitro experiments Extract preparation Extracts for the mutagenicity and the hyperseasibiliza: tion tests were prepared by cutting the bands in small pieces and subsequently putting them in sterile glass containers with the appropriate volume of extract, ‘medium under aseptic conditions. The extract mixture ‘was incubated ut approximately 80°C for 14 days. Once ily, the extraction battles were shaken carefully a few Mutagenicity ‘Testing for mutagenicity of a 0.9% NaCl extract of the PUUR material was carried out according to Ames in ‘Salmonelta typhimurium strains (33), and as a mamma Jian cell ene mutation test using mouse lymphoma cells [34] by an accredited laboratory.TABLE 1 Summary of experimental etlggs: bit inraaricalar implication, abit ACL ty 0d miipg ACL stay oy Mena Ana tr ‘oouaionse CRAB Omens Timm Wi In vivo animal experiments Hypersensibilization tests Hypersensibilization tests were performed in guinea pigs bby an accredited laboratory [35,36]. The 0.9% NaCl extract ofthe PUUR material was sed to test the dermal ‘sensitisation potential Animal implantation ‘A total of 35 adult New Zealand White rabbits were used. In the intraarticular implantation study, nine rabbits, age {6-9 months (4.5-S.5 kg) of both sexes were used. The remaining 26 animals were included in the rabbit ACL study (castrated males and females ofthe same age and weight). After being kept in single cages two weeks postoperatively, the rabbits were housed together and allowed free movement in a separate room for the remaining observation period. The rabbits were fed a standard dit with free access to food and water In the minipig ACL study, two female Gottingen ‘minipigs Elleguard Laboratory Pigs, Denmark), age two ‘years, weighing approximately 35 kg at time of surgery Were used. The pigs were kept in separate cages two weeks after surgery, and subsequently released together in a 100m. The food intake was controlled but the pigs had free access to water. The animal implantation ‘experiments ate summarized in Table L. AA animal experiments were approved by the Local Ethies Committe, Géteborg University Surgery Rabbit intraarticuler implantation Nine rabbits were operated on i two series (ria 1, and til Tl, n=3). Surgery was performed under general anesthesia using im.” injections of diazepam, 2Smgkg! bovt. (Stesolid®; §mgml~', Damex AS, CCopentagea, Denmark) and a combination of phentanyl and fluanizone, Imghg~! b.wt. (Hypnoem eth, Janssen Farmaceutika, Denmark). Both ind legs were Shaved and washed with 4% chloshexidine digluconate iibitane®, ICL, England) and 70% ethanol. Bilateral, the Knee joints were opened by a 3-4cm long medial paroputellar incision and the. patella was dislocated Jateraly. In trial I, a Tmm long piece of woven PUR band was implanted in each knee-joint, and sutured tothe synovial membrane in the medial par of the joint cavity, with size 4-0 Dexon (Davis and Geek, Hampshire, UK) sutures In ial I, «S-mm long PUUR band was tured. to the synovial membrane as described in trial 1, while the right kaee received a bundle of unwoven polymer fibers ofa similar weight, sutued tothe medial part of the synovial membrane with size 7-0 silk sutures (Davis and Geek, Hampshire, UK). After implantation, the knees were closed in separate layers and the synovial tissue and fibrous capsule sutured with size 6-O polyester sutures (Ti-Crone®, Davis and Geck, Hampshire, UK). Finally, the skin was closed with size 3-0 monofilament polyester sutures (Noval, Davis and Geek, Hampshire, UK). Postoperatively, antibioties (mike? bast, Inencillin, LEO®, Pharmacia, Sweden) and analgesics (0.0Smgkg~' bowt “Temgesic™ Rechkit andl Coleman, USA) were adminis- tered as single im. injections daly for three days, Rabbit ACL study ‘The anaesthesia and surgical preparation ofthe 26 abbits were performed us described above for the rabbit intearticulae implantation study. The PUUR bands were pre-souked in sterile saline for 30min before surgery. The knee-joints were opened by a medial ‘parapatellar incision and the patella was dislocated laterally. The ACL was identified and surgically removed. A tunnel, diameter 2.7mm, was made by a ‘pneumatic drill (miniriver, 3M Health Care, MN, USA) from the medial proximal part of the tibia through the tibial plateau, A second tunnel was made from the natual Jnteacondyla Femoral insertion of the ACL ending atthe lateral part ofthe femur. The bands were pulled through the tunnels in the tibia und femur and were fixed with a notin the tibial end, and a firm tension was applied before two staples fixated the band outside the femoral tunnel. Finally, the patella was relocated, the wound closed in separate layers and postoperative medication administered as described above forthe rabbit intraarti- cular implantation study. All hard tissue preparation was performed under generous irrigation with sterile saline (NaCI 9 mg/ml; ACO, Sweden) Minipig ACL study The animals were anesthetized with an injection of Ketamine hydrochloride im. (Ketalar® 30mg! 1m), diazzpam @Smgkg-! bow. Steslid™®, Smgml”', Dumex A/S Copenhagen, Dena) and a combination of phentany! and fuanizone iv. Img kg! bovt Hiypnorm Vet) along with endotracheal vet tion (N;0, 5 and 0,21). The ight ee was shaved and washed with 48 chlonhexidine dighiconate (Hibitane®, ICL, England) and 70% ethanol. The bands were pre= soaked in sterile saline 30min before suger. The sight 353Ince was opened by a medial parapAtellir incision and the patella was dislocated laterally. The ACL was Identified and surgically removed. Using a trephine rill, diameter 7.0mm, a tunnel was made from the medial proximal part of the tibia through the tibial plateau. A second tunnel was made from the natural intrachondylar femur insertion of the ACL ending atthe lateral part of the femur. A PUR ACL band was inserted and fixed with a stainless steel staple at both ends. The patella was relocated and the wound was closed in ‘separate layers. The synovial membrane and the fibrous ‘capsule were sutured with 3-0 T-Crone (Davis and Geck, Hampshire, UK) and the skin was closed with 3-0 Noval (Davis and Geck, Hampshire, UK). The left knee was left without surgery to function as a contol Preparation of specimens Rabbit intraarticular implantation Tn tral I, one rabbit hud to be killed after two months due to a pulmonary infection and was withdrawn from the study. The remaining eight animals were killed (two at ‘each observation time) after 3, 9, 13, and 18 months, respeatively, with an overdose of barbiturte (Mebomal®, ACO Likemedel AB, Solna, Sweden). ‘The implants with surrounding tissue were removed en bloc, and imamersed in buffered formalin (4%) for 24 In {vo animals (one snimal at rine months and one at 18 ‘months), the implant bunds were found. detached from the synovial membrane and only the tissue was ‘embedded and sectioned. Additionally, tissue from the lungs, Kidneys, and liver was obtained from six rabbits after 3,9, and 18 months, All specimens were embedded in paraffin and sections of ~ 5pm thickness were prepared and stained with hematoxylin and cosin for light microscopic evaluation Rabbit ACL study ‘One animal died postoperatively owing to the unesthesia. After one month, one animal was killed due to luxation ‘of the patella, and another one due to pneumonia. The remaining animals were killed after 6 months (wn = 2), 12 months (n= 3), 18 months (n= 6) and 24 months (= 12). The implants with surrounding tissue were removed en bloc and immersed in buffered formalin (4%) for 24h. The specimens were decalcified in EDTA, dehydrated in ethanol and subsequently embedded in paraffin. Sections of ~ 5m thickness were prepared ‘and stained with hematoxylin and eosin for light ‘microscopic evaluation Minipig ACL study Afier 24 months, the animals were Killed by a lethal injection of Ketslar® 30mgmi~' end potassium chloride. The knee joins were removed and immedistely ‘immersed in buffered formaline (4%) for two days. In ‘oder to obtain thin sections, an initial attempt 1 emincralize the tissve blocks with EDTA was under- taken, However, the process was abandoned due to an ‘unacceptable Tong time to complete the demineralization Process. Instead, the specimens were dehydrated in 354 ethanol, embedded in plastic resin (LR White, The London Resin Co, Hampshire, UK), and divided long- itudinally by sawing (Exakt® cuting and grinding equipment, Exakt Apparatebau, Norderstedt, Germany), Four ground sections (one from each joint) of ~ 15 ‘20pm thickness were prepared and stained with 1% toluidine blue (37) Results Tensile testing ‘The results of the tensile tests are presented in (Fig. 2) ‘Three bands were tested. The mean elongation at rupture ‘was 89% at a mean bretking load of 207 N. Cyclic loading The elastic properties of one woven band of three tested sare demonstrated in (Fig. 3). The elongation vs. cycle curves didnot show any tendency to excessive relaxation during the 50 repeated cycles tested, In vitro experiments Mutagenicity ‘The PUUR extract was found to be non-mutagenic in the ‘Ames test and the éa vitro mammalian cell gene mutation test Bat Ban Bandi 20 40 a 8010020 Extension (mm) Figure 2 Stes boavior of tee PUUR ACI. bn Extension (om) Figwe 3 Stein conrled cyl est behavior of « PUUR ACL Band.In vivo animal experiments, Hypersensibilization tests NNo evidence of delayed contact hypersensitivity was observed in the guinea pig experiment after treatment with the PUUR extract. Rabbit intraarticular implantation General clinical evaluation. ‘The eight animals wece in ‘good health with unaffected knees during the observation period. Macroscopical evaluation. The cartilage ofall facets of Doth the femur and the tibia was intact. No synovial reaction was noticed in the knees. Light microscopic morphology Lung, kidney, and liver. ‘The sections of the vita organs showed normal histology, without any indication of inflammatory reaction, Knee joints. At all observation times, the interface between the PUR fibers and the tissue was charaeter- ized by a mild foreign body reaction and a mild inflammatory response (Fig. 4(@)-{c)). In some of the seetions containing fiber bundles (Fig. S(a), lymphocyte collections were seen in a perivascular and implant- adjacent position. Even after 18 months, ao clear signs of degradation ofthe polymer was evident. Fibrous tissue ingrowth, mainly a non-vascularized collagenous tissue was detected after three months close to the surface of the implants. After 13- months, ‘vascularized, fibrous tissue ingrowth was seen at several locations even in the core ofthe implant (Fig. 4(6). ‘The tissue response to the fibers was characterized by fan encapsulation of the implant by a relatively thin fibrous tissue. After 18 months, a more well defined fibrous capsule sas surrounding the material than at ceutlier time periods (Fig. 4(a)). In general, the fibrous ccupsule was separated from the PUUR band by ‘macrophages and foreign body multinuclear giant cells (FBMGCs), Overall, there are only few, scattered inflammatory cells in the stromal tissue (Fig. 5(b)), ‘mainly macrophages and plasma cells. The synovial ‘membrane had « normal appearance but did sometimes present an attenuation or slight thickening (Fig. 5(€). Rabbit ACL General clinical evaluation, Apart from the three animals withdrawn from the study, the animals were all in good health with no signs of discomfor or instability ofthe knees during the observation period. Macroscopical evaluation. ‘The animal killed after one ‘month with patella dislocation showed synovial reactions ‘andexudation, while the animal with pulmonary infection hhad normal joints without signs of pathology. In the remaining animals, the cartilage ofall facets of both the femur and the tibia was intact with no signs of osteo- arthritis. No synovial reaction was noticed inthe Kaces. ‘At6, 12, 18, nd 24 months all rabbits had intact knees Figure 4 Mow of light micrographs fom the abit intmariur implantation sty a) 18 mont, Thin synovial membrane Cock stows) and an suey Inflammation fee Geni nroundng the ‘hod. Ingo tate son a ees ofthe und (gry are ith few gat ole che the implant surface. Bar= 100m (9) iteen ‘mort lngrovih floes connective awe win te cet paon GF the PUR and Small blood vee! densted by roms Bar= 100, (6) 18 months. Thin and ration free” synovial serra coset the Rr. Some fowign Soy malice giant (lls evo lve othe implant Bar= 70 jn tnd no signs of joint damage. At six months the overall appearance revealed an integrated, intact PUUR band in both the tibia and the femur without any adverse macroscopic reactions in nether the bone aor the joits Fig. 6). Light microscopic morphology. LM morphology at all stages revealed an integrated PUUR band in both the bone and in the soft tissue (Fig. 7(a), (b)). At 6 and 12 months, bone formation was observed in close contact with the PUR fibers at the outer surface of the bands Within the cortical passage, without signs of interfering 355Fpwe § Moun of compensate policed ig micrographs oH and Sued praises fhe rab nual impataton ‘uy. (0) vee ment, Survey of PCL Rie bane sree by Bar= 100 ( ane moths: Some FENGCs let the plant Bur=100pm (e) Survey micah 5 ment PUUR Band with some macophager and FEMGCr lee to the suze Alnoe soft tissue (Fig. 7(4)). Moreover, connective tissue ingrowth was frequently observed between PUR fibers along the course of the band with ingrowth of blood vessels at several locations (Fig. 8). At the earlier Times, no sigas of material degradation was detected. Afier'24 months, the fcst signs of degradation of the polymer was evident, when the continuity of the fibers were ocessionally broken (Fig. 9). 356 Fiore Macroscopic appesrince of PUUR band in abi ine i. sit month afer operon, Note eile game peters with teal eclarerage ia jos Minipig ACL study General clinical evaluation. During the two year ‘observation perio, the knees were stable and no clinical signs of discomfor. was reported. Macroscopical evaluation. ‘The cartilage of all facets of both the femur and the tibia was intact. No synovial reaction was noticed Light microscopic morphology. The PUR bands were well incorporated in the osseous host tissue. At the ends of the band (in the cortical passage), the band had a liscontinuous appearance, with bone present at the peviphery ofthe band (Fig. 10()) In several parts of the sections, a close contact between the PUUR fibers and the newly formed bone was observed. Inthe core of the band, the majority of the PUUR fibers seen in the ground sections were intact, and ‘brows connective tissue was diseemible between the PUUR fiers (Fig. 10(0)). The connective tissue had a dense, oriented, ligament-tike structure, with only few cells between the parallel oriented collagenous bers ig. 106). Tn both ACL and contol sections, the articular catilage showed a normal morphology without signs of. pathology. Discussion In the present study, we demonstrate the mechanical properties and the first in vilro and in vivo results of & ‘degradable PUR fiber with the intended use in ACL reconstruction. The combination of the chemical ‘composition, fiber spinning and textile manufacturing generates the final properties of the band (38]- Earlier augmentation devices, degradable or non-degradabl, have a rigid texture and thus not the mechanical properties of a normal ACL or a tendon graft (24). The rigidity directs most of the loading to the augmentation device, with failure due to stress-shielding or fatigue of the device asa consequence (23). The novel PUUR band has a similar elasto-mechanical loading profile as 2 hhuman ACL tested post mortem (24), and after cyclic Joling in 50 repetitive eycles, no relaxation or fatigue ‘vas observed, To our knowledge, the newly developedFigure 7 1M Micrograph of Wslogial won of bit ke with POUR band 6 nots otervatio ine) pln pt) Han Giseon sing. Bar=A0D jm, (0) Enlarge are fn i 70). ising ste ingrowth ttween PUUR fer B= 1009 2) Enlarge wes frm Fg) demortting ingrowth Fe eee her: Ba 100, PUUR band is the fist synthetic ligament device with suoh a loading profile (39, 40}, ‘Among the most commonly used autografts in ACL reconstruction are free pater tendon grafts. A. criical Period of time occurs 3 to 6 months after grafting, during ‘evascularization and reorganization ofthe fee patellar tendon graft. At this time, the graft displays reduced ‘mechanical strength with a rtk for residual elongation, and consequently instability of the knee (41), Accordingly, a degradable augmentation device could be used in conjunction with the tendon graft to provide igre 8 LM Mr, Rabbit ee jot with PUUR ban afer 2 ‘tween raining PUUR Rho, Bur= 503m sere 9 Mirra Secon sowing bit hee with PLUK device ter 18 conte, Conctive ti between PUUR Shere. Note the Shepton fhe bers compare ih hee mats main ie (Fe 1). Bar 1004 resistance to the mechanical oad’ during the time for revascularization and reorganization ofthe tissue Wis imperative that w new degradable material is well tolerated and incorporated in the host tissue, As the synovial membrane is a richly vascularized tissue, it reacts promptly with an inflammatory reaction to any ‘mechanical or chemical stimulus. To test for this, piece ofthe band or bundle of fibers was sutred tthe synovial membrane of the knee in order to detect any adverse reactions. Despite the close contact between the band and the membrane, no joint reaction or macroscopic inflammation was demonstrated. However, microscopic ‘examination ofthe sections showed that in the area close to an implant, macrophages and FBMGCs were preset The mechanism for the focal accumblation of Iympho- cytes, occasionally seen at 13 and 18 months, is not Known, nor their role atthe site. One possibility may be frition between the band and the synovial membrane as the PUUR material only was sutured with two sutures, possibly allowing movement and friction. The presence of FBMGCS in association withthe PUUR sutface is not surprising, since itis likely that the slowly degrading PUUR present a large, unphagocytosable object. In addition, a rough surface topography may favor FBMGC formation and attachment to the surface, and itis likely 357Figure 10 Ligh mirorap from road section (mii ACL sy 21 mont) Bone fom rte of eens iseron remount Roe of Be PUUR band. Bar=300ym. (@) Connective Uns (rt) Setvees he es fe PUUR ta located th cena ats of te ‘ie Intact prt of te PUUR bod noted rs) Bat = 10 i that the fiber sueface topography will change during the process of degradation, Inthe rabbit studies, where the PUR bands were used. as a full ACL prosthesis, the knee joint function sas intact even after24 months. The absence of osteoarthritis indicates koee joint stability, as instability of the joints is. known to result in degenerative changes in the cartilage [42,43], At 24 months, some decay of the fibers was observe, indicating possible degradation ofthe PUR ‘material, and the theoretical degradation time of the band. {in vitro implies that the remsining mechanical strength is negligible [38]. Atthis observation perio, newly formed connective tissue was demonstrated at several locations bridging the extension of the natural ACL. This observation suggests that cells have migrated into the implanted PUR band and formed new tstue atthe time of degradation and, albeit speculatively, possibly carry pants ofthe biomechanical load Formation of new vessels between the fibers in the band was detected at several locations, without the preseace of inflammatory cells, both a the periphery and in the center of the PUR band. This implies tht the Fibers are tolerated by the host, and further, that angiogenesis is concomitant with somal cell migration, issue formation and differentiation. AS in the rabbit, the 358 ingeronopiealy ntact knee joint ofthe minipigs time Of guthanasia, indicated Mable knee joint fonction {2°a5) In opit of the species differences, the miniig displayed sar histological pctre, with ove fomation in the efile tonne and surounding the PUUR band. In the central pars ofthe PUR band, ligamentike connective tise ingrowth was observed between the fers o ‘Ate 24 month, signs of ber degraton wa een in the mbit ACL study. However, in the minipig ACL tod no clea signs of degridation ofthe fibers was Sppaent afer 24 month. Ths inconsistency may be felted to species differences in regard ofthe frequency Gf Knee join motion. Given tat the loos of molecular srvght occurs ahead of man loan und ola degra tion 4], longer observation time is necessary 10 demonstrate mass. degradation histologically ‘Accelerate hydrolysis experiment, to be presented in 4 forthcoming publication [38], have demonstted dscreate in molecular weight and sltentons of te rmechanieal properties ofthe PUUR material, which is Consistent with the significant degradation of the material ster 24 months in viv. In conclision, «degradable PUUR band. has been developed to serve in ACL recontution. In ths dy we have demonstrated mechanical stiffness and elastic finctin siler to nonmal bnman ACL, in wre biocompatibility and tasue ingrowth, and # preserved join function over 24 months in abit and pgs. Human Clinica als with ACL reconstuction using the PUUR bund ac in peor. Acknowledgment We are grateful to Professor Peter Thomsen, Insitute fof Anatomy & Cell Biology, Goteborg University, for his scientific expertise and advice related to biocompatibility References 1 J.A, FEAOINO. ja "The Crs Ligaments eed by JA Fagin Je (Choc Livingstone lc. New York 1985 2, PARAMUS a. IARVENEN Clin Rhea 2(1989)251— 260 172 1985) 158-163 4. C.FNK €. MOSER and K.P, SENEDETTO, UnfleAre. 7 (iss) 357-36 ousavi China (990) 92-58 © amines tasi to. somiasdat Spel 18 (tren es {oe nwa 9 OB) eFa57. foo. somes i 19 (991) 586-60, © Mak tuewmen. tna times vo Thonn armen ar siete 11 EN cones AAraan nena 12 ee rOLKERSON an KANORLAND,Arthropy (1998)