Knee meniscal transplantation.
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Biomedical subjects
Publications and source records attributed to G E Friedlaender.
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This study examined the effects on the biomechanical parameters of fracture healing of a single dose of 900 rad (the approximate single-dose equivalent of 2,500 rad in 10 divided doses), given 1 day prior to closed fracture of the femur. The femurs were recovered at 2, 3, 4, 8, and 16 weeks after fracture and were mounted and tested to failure in torsion; the results were compared with those in nonirradiated controls from a previously published study. Prefracture irradiation delayed the progressive increase in biomechanical parameters of fracture healing. The delay was statistically significant up to 8 weeks after fracture. At 4 weeks, the normalized torque was 44% that of intact bone in the treated group compared with 75% for the control group. Sixteen weeks after fracture, the biomechanical and histological parameters of fracture healing of the irradiated femurs were no different from those of the nonirradiated controls. Within the treated group, the irradiated fractures remained significantly weaker than their contralateral intact bone at all time intervals, with a torque of only 79% that of intact bone at 16 weeks. Thus, femoral fractures in rats healed (or regained substantial strength) following palliative doses of radiation delivered 1 day prior to injury, but the repair process was delayed compared with that of nonirradiated controls.
The success of total hip arthroplasty has been well documented. Aseptic loosening remains the major long-term problem that can lead to significant bone loss and structural deficits. Bone graft has been used with increasing frequency to reconstruct these difficult cases. In this review, the authors detail the biology, biomechanics, and banking of bone grafts. A summary of currently available data on the clinical result of autograft and allograft in reconstructive hip surgery is presented.
Osteochondral allografts evoke immune responses. The nature of these immune responses and their biologic significance are still only partially understood. It is clear, however, that cell surface antigens of the major histocompatibility complex represented on the cellular elements of bone grafts cause T-cell activation, specifically those of the suppressor/cytotoxic phenotype. In numerous animal models, the most immunogenic bone allografts (mismatched, fresh) have demonstrated the poorest clinical and biologic outcomes, while more closely matched and/or grafts treated to reduce immunogenicity (frozen, freeze-dried) have more successfully incorporated. These observations support the hypothesis that immune responses against bone-graft related antigens have biologic significance and that reducing these responses may improve clinical results.
Ibuprofen is a widely used cyclo-oxygenase inhibitor in clinical practice. It has been demonstrated by others to have an inhibitory effect on fracture repair in animals. In the present study, we were unable to demonstrate any significant alterations in fracture biomechanics as measured by torsion testing and fracture stage in mature Sprague-Dawley rats treated with 30 mg/kg/day oral dose of ibuprofen, starting 3 days following fracture, over a 12-week time interval. Fracture histology and serum osteocalcin levels were no different in treated animals than control animals. Furthermore, histomorphometric parameters of bone remodeling, including bone volume and bone formation rate in the intact tail vertebrae of these animals with unilateral femur fractures, were no different between treated and control animals.
The effects of single-dose local irradiation on the biomechanical properties of closed femoral fractures were studied in 75 mature Sprague-Dawley rats. Ten days after fracture, the rats were irradiated with 900 rads at 250 kV to the entire fractured femur. At 2, 3, 4, 8, and 16 weeks after fracture, both fractured and contralateral intact femurs were recovered and evaluated biomechanically by testing to failure in torsion. Results were compared with those from a similar study involving fractures irradiated 3 days after fracture as well as nonirradiated control fractures. Fracture healing progressed faster when irradiation was delayed 10 days than when delayed 3 days, and control fractures healed more rapidly than after either delay. In the 10-day delay group, fractures showed greater strength than did those in the 3-day delay group at 8 weeks, but the strength of irradiated fractures in both groups was similarly depressed at 16 weeks, with a maximum torque well below that of control fractures. These results suggest that delaying radiation exposure of a fracture may mitigate short-term deleterious effects on fracture repair, but that long-term results may be similar to those associated with expeditious irradiation.
The capacity of fresh murine allogeneic bone to induce a specific immune response in vitro was studied. T-cells stimulated by allogeneic bone in vitro were collected and were characterized for state of activation, cell-surface phenotype, and antigen specificity. The stimulating antigens were determined by genetic mapping with use of recombinant inbred strains of mice and by blocking of mixed lymphocyte cultures with use of neutralizing antibodies. Purified T-cells were cultured alone or with allogeneic or syngeneic bone. In some experiments, the bone marrow was removed before in vitro culture. Responding cells were recovered after a secondary exposure to the stimulating bone. Primed cells were used immediately or cell-lines were developed. The data demonstrated that (1) allogeneic bone activated T-cells and induced their proliferation; (2) bone-induced proliferation of T-cells was specific for antigens that map to the major histocompatibility complex of the bone donor; (3) within the major histocompatibility complex, the antigens responsible for proliferation of T-cells were apparently class-I and class-II determinants; (4) removal of bone-marrow cells had no effect on the ability of that bone to stimulate alloreactivity; and (5) all of the alloreactive T-cells had the cell-surface phenotype Thy-+ CD8+ CD4-.
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The effects of a single dose of irradiation on the biomechanical parameters of the fracture healing process were studied in a rat model. Intramedullary pinning was performed before production of a closed femoral midshaft fracture. The experimental group was exposed to 900 rad 3 days after fracture and was compared with a control group with a similar fracture that received no irradiation. Animals were killed at intervals ranging from 2-16 weeks after surgery and the bones were tested until failure in torsion. In the irradiated groups, a delay of 4 weeks was noted in the biomechanical parameters associated with fracture healing (torque to failure, torsional stiffness, angle to failure, and biomechanical stage). Despite this delay in the normal temporal progression, the staging and stiffness approached normal controls within an 8-week period. However, the torque to failure remained below normal levels at the conclusion of this study. These results differ from a previous study using an open fracture model.
Allogeneic bone from Sprague-Dawley rat femurs was subjected to levels of freezing and/or irradiation that are known to have produced changes in the associated immune responses to these grafts. This bone was transplanted into an experimentally created gap in the femur of Lewis rats. The subsequent healing of the transplants in the Lewis rats was studied at 2, 4, 8, and 16 weeks after transplantation using torsion testing to failure. There was no clear advantageous biologic response in the union of the grafted material accompanying the alterations in immunologic response as measured by biomechanical testing of the proximal osteosynthesis site in torsion. The torsional strength of all of these groups remained lower than that of intact bone. Furthermore, none of the frozen and/or irradiated allografts exceeded the strength of the fresh allograft at a statistically significant level.
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The production of tumors through solid-state mechanisms has been demonstrated in experimental animals, but foreign body tumorigenesis has not been proven definitively in man. The authors report three patients with angiosarcoma that occurred in intimate association with foreign material retained for prolonged periods. Although several etiologic factors have been defined in angiosarcoma, foreign bodies generally are not appreciated to have this potential. Review of the literature disclosed six cases of angiosarcoma and 40 cases of sarcomas of other histologic types associated with foreign material, with latency periods of from 4 months to 63 years. Implanted foreign material thus should be considered capable of inducing virtually any form of sarcoma in humans.
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This article presents the hypothesis that bone, like other soft tissue, is rejected in an immunologic fashion. However, because bone is mineralized, it presents unique aspects that are also dealt with by the immune system. The article goes on to review the immunologic considerations of bone allograft reactivity.
Bone banks are now available at local and regional levels that can supply tissues acquired from cadaveric and live donor sources. With appropriate donor selection criteria and banking techniques, these tissues are both safe and efficacious. Understanding the nature of the banking process, particularly the influence of various preservation techniques on biology and biomechanics, as well as knowledge of the incorporation process should lead to selection and an appropriate application of these tissues in reconstructive surgery about the hip. The availability of these allografts has extended our ability to devise salvage procedures and increasingly innovative approaches to numerous reconstructive challenges.
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Autogenous cancellous bone graft alone or in combination with electrical stimulation is commonly employed yet there exists no conclusive data that the strength of the healing defect is actually modified. The authors examined three groups of paired canine femurs that were torsion tested to failure. Group I (in vitro): an intact femur was compared to a standard defect; Group II (in vivo): a defect alone was compared to a defect plus graft killed at eight weeks; Group III (in vivo): a defect plus graft was compared to a defect graft plus Osteostim (BGS Medical Corp., Milwaukee, Wisconsin) implantable stimulator killed at eight weeks. In Group I the defect decreased the average strength 45% (p = 0.005); in Group II the grafted defect decreased the strength 20% (p = 0.121); in Group III the defect graft plus electrical stimulation increased strength 4% (p = 0.669). At eight weeks, bone grafting, alone or with electrical stimulation did not statistically increase the torsional strength of the healing bony defect.
Storage of bone for use as allograft has become an important endeavor because banked bone is becoming increasingly useful and popular as a substitute for, or as a supplement to, autograft bone. Methods have been developed for safe and reliable bone banking, including standard criteria for acceptable donors, proven techniques of retrieval of tissue, and appropriate storage facilities and conditions. In contrast, cartilage banking is still an investigative procedure, but current research may provide more effective approaches to maintaining viable cells during freezer storage of osteochondral allografts.