Myriad molecular, cellular, and physiological processes underlie the inflammatory and osteolytic processes induced by particles of biomaterials resulting from the wear of implants such as total joint replacement prostheses. The objective this study was to investigate the role that the complement system may be playing in these phenomena. The aim was to evaluate the degree to which particles of selected orthopaedic materials--high density and ultrahigh molecular weight polyethylene, polymethylmethacrylate, and commercially pure titanium--cause the elevation of a key complement molecule, C3a, in an in vitro assay that directly measured the concentration of C3a. The results demonstrated that HDPE particles, at high concentration, are capable of causing the elevation of C3a in the in vitro assay. This finding is discussed in the context of other work and the mechanics of the complement system as it may affect the osteolytic process.

Two rat models were used to characterize tissue-specific reactions to particles of bone-substitute materials: one for osteocompatibility in a healing tibial wound and the other in a heterotopic. subcutaneous Site. Small. unicortical tibial wounds in rats healed spontaneously. beginning with the rapid proliferation of intramedullary woven bone. That temporary bone was resorbed by osteoclasts and finally. the cortical wound was healed with lamellar bone and the medullary space was repopulated with marrow. When various particulate materials were implanted into fresh wounds. three types of reactions were observed. (1) Demineralized bone powder(DBP) and non-resorbable calcium phosphate (nrCP) were incorporated into the reactive medullary and cortical bone. (2) Polymethylmethacrylate (PMMA) particles were surrounded with a fibrous laver, but did not impair bone healing. (3) Polyethylene (PE) shards and resorbable calcium phosphates (rCPs) were inflammatory and inhibited osseous repair.Subcutaneous sites showed osteoinductive, fibrotic. or inflammatory responses to these materials. Only DBP induced endochondral osteogenesis subcutaneously. The nrCP evoked a fibrous reaction. In contrast. rCPs, PMMA. and PE shards generated inflammatory reactions with each particle being surrounded by fibrous tissue and large multinucleated giant cells.In conclusion. only DBP showed osteoinductive as well as osteocompatible properties. The nrCP was osteocompatible. The rCPs Stimulated various degrees of inflammatory responses. PMMA was osteocompatible and did not interfere with the bone healing process. PE was not osteocompatible and generated foreign body reactions in both sites. Use of the two sites distinguishes osteoinductive. osteocompatible. and inflammatory properties of particles of bone-substitute materials. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

The aim of this study was to test the hypothesis that a tight seal between bone and implant will eliminate the avenue of particle migration around stable implants. Three types of implants were used in rabbits (polished press-fit Ti-6Al-4V or plasma-sprayed hydroxyapatite [HA]-coated Ti-6Al-4V) or doughy stage polymethyl methacrylate (PMMA). Implants were placed in the condylar notch. Each animal received an intra-articular injection of high density polyethylene (PE) particles (10(8) in 0.4 mL; mean size 4.7 microns) at 4 and 6 weeks postoperatively. Eight weeks postoperatively, peri-implant tissues were examined for PE particles and osteolysis. In all cases, intracellular PE particles were seen at the bone-implant interface and within marrow. No osteolysis was observed. Bone apposition was determined by computerized image analysis. There was no significant difference in the percentage of bone apposition (+/- SD) among the three groups of implants: Ti-6Al-4V (68% +/- 19%), HA-coated Ti-6Al-4V (70% +/- 10%), and PMMA (59% +/- 12%). These results indicate that a polished Ti-6Al-4V surface is as effective as PMMA or HA coating in limiting migration of PE particles around stable osseointegrated implants in rabbits.

The objective of our study was to evaluate reparative tissues formed in chondral defects in an adult canine model implanted with cultured autologous articular chondrocytes seeded in type I and LI collagen-GAG matrices. Two defects were produced in the trochlea grooves of the knees of 21 dogs, with cartilage removed down to the tidemark. This study includes the evaluation of 36 defects distributed among five treatment groups: Group A, type II collagen matrix seeded with autologous chondrocytes under a sutured type II collagen flap; Group B, type I collagen matrices seeded with chondrocytes under a sutured fascia flap; Group C, unseeded type I collagen matrix implanted under a sutured fascia flap; Group D, fascia lata flap alone; and Group E, untreated defects. All animals were killed 15 weeks after implantation. Six other defects were created at the time of death and evaluated immediately after production as 'acute defect controls'. In three additional defects, unseeded matrices were sutured to the defect and the knee closed and reopened after 30 min to determine if early displacement of the graft was occurring; these defects served as 'acute implant controls'. The areal percentages of four tissue types in the chondral zone of the original defect were determined histomorphometrically: fibrous tissue (FT); hyaline cartilage (HC); transitional tissue (TT, including fibrocartilage); and articular cartilage (AC). New tissue formed in the remodeling subchondral bone underlying certain defects was also assessed. Bonding of the repair tissue to the subchondral plate and adjacent cartilage, and degradation of the adjacent tissues were evaluated.There were no significant differences in the tissues filling the original defect area of the sites treated with chondrocyte-seeded type I and type II matrices. Most of the tissue in the area of the original defect in all of the groups was FT and TT. The areal percentage of HC plus AC was highest in group E, with little such tissue in the cell-seeded groups, and none in groups C and D. The greatest total amount of reparative tissue, however, was found in the cell-seeded type II matrix group. Moreover, examination of the reparative tissue formed in the subchondral region of defects treated with the chondrocyte-seeded collagen matrices (Groups A and B) demonstrated that the majority of the tissue was positive for type II collagen and stained with safranin O. These results indicate an influence of the exogenous chondrocytes on the process of chondrogenesis in this site. In all groups with implants (A-D), 30-50% of the FT and TT was bonded to the adjacent cartilage. Little of this tissue (6-22%) was attached to the subchondral plate, which was only about 50% intact. Remarkable suture damage was found in sections from each group in which sutures were used. Harvest sites showed no regeneration of normal articular cartilage, 18 weeks after the biopsy procedure.Future studies need to investigate other matrix characteristics, and the effects of cell density and incubation of the seeded sponges prior to implantation on the regenerative response. (C) 1998 Elsevier Science Ltd. All rights reserved.

The orthopedic problem of restoring damaged articular joint surfaces remains unsolved. One technique aimed at cartilage regeneration, which has been introduced clinically, uses autologous chondrocytes grown in culture and periosteum to treat defects made to the depth of the calcified cartilage. In this study we applied a similar treatment to 34 adult dogs and analyzed the course of healing at five time points up to 18 months, Two sets of controls mere included: (1) periosteum without cells and (2) empty defects. Histology showed healing generally to occur in three phases: (1) a proliferative phase (established by 1.5 months) in which reparative tissue was formed, (2) a phase of remodeling (found at 3 and 6 months) in which hyaline and articular cartilage were regenerated, and (3) a phase of degradation (observed predominantly at 12 and 18 months) in which the reparative tissue and surrounding cartilage appeared to become progressively damaged, Treated groups at 3 and 6 months contained more hyaline cartilage than untreated controls, but there was no evidence of a positive effect of periosteum or cultured autologous chondrocytes at 1 year and longer.

Synthetic and natural absorbable polymers have been used as vehicles for implantation of cells into cartilage defects to promote regeneration of the articular joint surface. Implants should provide a pore structure that allows cell adhesion and growth, and not provoke inflammation or toxicity when implanted in vivo. The scaffold should be absorbable and the degradation should match the rate of tissue regeneration. To facilitate cartilage repair the chemical structure and pore architecture of the matrix should allow the seeded cells to maintain the chondrocytic phenotype, characterized by synthesis of cartilage-specific proteins. We investigated the behavior of canine chondrocytes in two spongelike matrices in vitro: a collagen-glycosaminoglycan (GAG) copolymer produced from bovine hide consisting of type I collagen and a porous scaffold made of type II collagen by extraction of porcine cartilage. Canine chondrocytes were seeded on both types of matrices and cultured for 3 h, 7 days, and 14 days. The histology of chondrocyte-seeded implants showed a significantly higher percentage of cells with spherical morphology, consistent with chondrocytic morphology, in the type II sponge at each time point. Pericellular matrix stained for proteoglycans and for type II collagen after 14 days. Biochemical analysis of the cell seeded sponges for GAG and DNA content showed increases with time. At day 14 there was a significantly higher amount of DNA and GAG in the type II matrix. This is the first study that directly compares the behavior of chondrocytes in type I and type II collagen matrices. The type II matrix may be of value as a vehicle for chondrocyte implantation on the basis of the higher percentage of chondrocytes retaining spherical morphology and greater biosynthetic activity that was reflected in the greater increase of GAG content.

We retrospectively reviewed the clinical and radiographic results of total hip arthroplasty with cement in patients with juvenile rheumatoid arthritis who were less than thirty years old at the time of the index procedure. Thirty-nine patients (sixty-six hips) were managed with this procedure at our institution between 1971 and 1983. Six patients (eleven hips) died before a minimum of ten years of follow-up; the remaining thirty-three patients (fifty-five hips) were followed for at least eleven years. Twenty-eight patients (forty-six hips) had at least one original component in situ after an average duration of clinical follow-up of 15.1 years, and twenty-three of these patients (thirty-eight hips) were followed radiographically for an average of 14.7 years. At the time of the latest follow-up examination, all twenty-eight patients were able to walk outside the home; twenty of these patients (thirty-five hips; 76 per cent) had no pain with activity, and eight patients (eleven hips; 24 per cent) had mild-to-moderate pain with activity.Over-all, twelve (18 per cent) of the sixty-six femoral components and twenty-three (35 per cent) of the sixty-six acetabular components were revised after an average of 12.8 and 11.8 years, respectively. The fifteen-year survival rate for the femoral components was 85 per cent with revision or radiographic loosening as the end point. The fifteen-year survival rate for the acetabular components was 70 per cent with revision as the end point and 61 per cent with revision or radiographic loosening as the end point.The benefits of total hip arthroplasty were maintained over the long term in most of our patients who had juvenile rheumatoid arthritis. However, the durability of the components in these young patients remains a concern.

This study directly compared the behaviour of chondrocytes in porous matrices comprising different collagen types and different pore diameters. There was a dramatic difference in the morphology of the cells in the type I and type II collagen matrices. The cells in the type II collagen matrix retained their chondrocytic morphology and synthesized glycosaminoglycans, while in the type I matrix the chondrocytes displayed a fibroblastic morphology with less biosynthetic activity than those in the type II. Small pore diameter affected morphology initially in the type I matrices and showed a higher increase of DNA content, but with time the cells lost the chondrocytic morphology. Our results demonstrate the marked influence of collagen type and pore characteristics on the phenotypic expression of seeded chondrocytes.

BENZ, ERIC B. B.A.†; SHERBURNE, BRADFORD M.D.‡; HAYEK, JIHAD E. M.D.‡; FALCHUK, KENNETH H. M.D.§; SLEDGE, CLEMENT B. M.D.§; SPECTOR, MYRON PH.D.§, BOSTON, MASSACHUSETTS Author Information

In this study a canine model was developed to investigate the nature of early healing responses to both chondral and osteochondral defects and to evaluate the tissue regenerative capacity of cultured autologous chondrocytes in chondral defects. The healing response to surgically created chondral defects was minor, with little cellular infiltration. In contrast, osteochondral defects exhibited a rapid cellular response, resulting ultimately in the formation of fibrous tissue. The lack of significant cellular activity in chondral defects suggests that an evaluation of the capacity of cultured autologous chondrocytes to regenerate articular cartilage is best studied in chondral defects using the canine model. When dedifferentiated cultured articular chondrocytes were implanted into chondral defects, islands of type II collagen staining were demonstrated in the regenerative tissue within 6 weeks. The relatively early expression of cartilage specific markers by the implanted chondrocytes, coupled with the inability of untreated chondral defects to repair or regenerate, demonstrates the utility of the canine model in evaluating novel materials for cartilage repair and regeneration.

Beta-particle dosimetry of various radionuclides used in the treatment of rheumatoid arthritis was estimated using Monte Carlo radiation transport simulation coupled with experiments using reactor-produced radionuclides and radiachromic film dosimeters inserted into joint phantoms and the knees of cadavers. Results are presented as absorbed dose factors (cGy-cm2/MBq-s) versus depth in a mathematical model of the rheumatoid joint which includes regions of bone, articular cartilage, joint capsule, and tissue (synovium) found in all synovial joints. The factors can be used to estimate absorbed dose and dose rate distributions in treated joints. In particular, guidance is provided for those interested in (a) a given radionuclide's therapeutic range, (b) the amount of radioactivity to administer on a case-by-case basis, (c) the expected therapeutic dose to synovium, and (d) the radiation dose imparted to other, nontarget components in the joint, including bone and articular cartilage.

Intra-articular radiation treatment using dysprosium-165 ferric hydroxide macroaggregate has been performed on eight patients with refractory synovitis of the ankle. Seventy-five percent (six patients) responded well to the treatment, and there were no complications from the injection. Although ankle synovectomy is not often indicated, those patients with rheumatoid synovitis without significant joint destruction respond favorably to radiation treatment.

The long-term complications related to the patella were retrospectively evaluated for 891 knees (684 patients) that had had a total arthroplasty, with or without resurfacing of the patella, with use of an unconstrained, condylar, posterior-cruciate-preserving prosthesis. The study population comprised two groups of patients who were similar in size, age, sex distribution, and diagnosis. One group (396 knees [303 patients]) had had a total knee arthroplasty with patellar resurfacing and the other group (495 knees [381 patients]) had had the same procedure without resurfacing. The average duration of follow-up was six and one-half years (range, two to fifteen years). The decision to resurface the patella was based on subjective inspection of the articular surface and on assessment of patellar tracking at the time of the operation. Resurfacing was performed if there was loss of cartilage, exposed bone, gross surface irregularities, or tracking abnormalities. Complications occurred an average of three years (range, immediately postoperatively to nine years) after the operation in the group that had had resurfacing and an average of four years (range, immediately post-operatively to ten years) postoperatively in the group that had not had resurfacing. In the group that had had resurfacing, there was loosening of the patellar component in five knees, patellar subluxation in four knees, fracture of the patella in three knees, rupture of the patellar tendon in three knees, and chronic peripatellar pain in one knee. In the group that had not had resurfacing, the complications included patellar subluxation in five knees, rupture of the patellar tendon in two knees, and chronic peripatellar pain in fifty-one knees.(ABSTRACT TRUNCATED AT 250 WORDS)

This study reports findings on joint fluid enhancement after intravenous administration of gadopentetate dimeglumine. Ten subjects were studied: two asymptomatic volunteers and eight patients with suspected meniscal tears. The subjects underwent imaging at 1.5 T before, immediately after, and 42-60 minutes after intravenous administration of gadopentetate dimeglumine. The rate of fluid enhancement was assessed in three subjects, and the effects of exercise were studied. All subjects exhibited enhancement of joint fluid. Mean fluid enhancement for patients was 137% on initial and 262% on delayed images obtained after exercise. Exercise increased the rate and degree of fluid enhancement and distributed contrast material uniformly throughout the joint. The arthrographic effect of the fluid enhancement increased the number of perceived cartilage defects. This study documents enhancement of joint fluid in healthy subjects and in those with effusions. The arthrographic effect may provide a more convenient alternative to intraarticular injection of gadopentetate dimeglumine for MR arthrography.