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Biomedical subjects

Thomas W Bauer

Publications and source records attributed to Thomas W Bauer.

At least 37 records · Page 2Linked to original sources

The osteocyte.

Osteocytes are the most numerous cells in mature bone and have the potential to live as long as the organism itself. However, study and subsequent understanding of osteocyte biology has been thwarted by the remote location of the cell in the mineralized matrix. This review is intended to synthesize current understanding of osteocyte biology and to suggest future paths that will promote understanding of this obscure cell and translation of knowledge to disease prophylaxis and management.

Animals↗

Lumbar intervertebral body fusion cages: histological evaluation of clinically failed cages retrieved from humans.

BACKGROUND: Although interbody cages are widely used, there is little histological documentation of the tissue within cages in the human spine. The purpose of this study was to describe the contents of retrieved, clinically failed, interbody cages from human patients, with special reference to the influence of graft type on the viability of bone in the cages. METHODS: Seventy-eight cages that had been retrieved from forty-eight patients were analyzed. There were eight carbon-fiber cages and seventy threaded metal cages. Of the sixty-seven cages for which information about grafting was available, fifty-six had been packed with autograft only, six had local autograft mixed with demineralized bone matrix, four had allograft, and one had demineralized bone matrix only. The indications for cage retrieval included a failed fusion, malposition or migration of the cage, trauma (a compression fracture at the fusion site), low-back pain, progressive spondylosis, nerve-root impingement, and/or infection. The cages had been in situ for an average of twenty-two months. Undecalcified sections through the center of each plastic embedded cage were reviewed, and the approximate areas occupied by viable bone, necrotic bone, fibrocartilage, hyaline cartilage, fibrous tissue, and graft substitute were visually estimated. Debris particles were estimated by a semiquantitative scoring system. RESULTS: Seventy-one of the seventy-eight cages showed evidence of vascular ingrowth and areas of histologically viable bone, representing incorporating bone graft. The average area occupied by viable bone was 44% (range, 0% to 80%). In some cages, relatively large fragments of cortical bone graft were associated with only minimal new-bone formation. Fibrocartilage occupied up to 50% of the available area in these failed cages. Some cages also contained small fibrocartilage seams connecting segments of bone in a pattern that suggested motion in vivo. In thirty-one of the seventy-eight cages, > or = 5% of the available area was occupied by hyaline cartilage, probably from vertebral end plates or facet joints. CONCLUSIONS: While this study was not designed to test the efficacy of cages or of bone graft, the prevalence of hyaline and fibrocartilage in these failed cages illustrates the importance of graft and graft-site preparation to maximize bone-graft incorporation. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.

Adult↗

Histologic evaluation of human vertebral bodies after vertebral augmentation with polymethyl methacrylate.

STUDY DESIGN: Histologic documentation of vertebral bodies retrieved from human patients. OBJECTIVES: The purpose of this study is to illustrate the histologic findings of two cases in which vertebroplasty and/or kyphoplasty had been performed. SUMMARY OF BACKGROUND DATA: There are a number of controversies to vertebral augmentation, including the use of inflatable bone tamps, use of nonstandardized polymethylmethacrylate (PMMA) preparations, the extent and significance of thermal necrosis, any foreign body reaction, and cement extravasation. METHODS: Four vertebral bodies from two cases ranging from 1 month to 2 years after surgery were analyzed histologically. Microscope slides of retrieved vertebral bodies were reviewed with special reference for evidence of thermal necrosis, foreign body reaction, migration of cement, cement voids and fractures, and for the influence of the bone tamp on adjacent bone. RESULTS: The cancellous bone around the cement of the kyphoplasty specimen showed good density, suggesting that the tamping had displaced bone, essentially autografting the space around the cement. Bone immediately around the cement did not show extensive necrosis, but there were a few spicules of necrotic bone associated with creeping substitution, suggesting either thermal effect, the original fracture, or displacement of bone by the procedure. Foreign body giant cells and macrophages were identified in the fibrous membrane around the PMMA in all segments. These cells contained material consistent with cement particles and/or barium sulfate. Particles were also present within vascular spaces. CONCLUSIONS: To our knowledge, these cases are among the first published reports of human histology after vertebral cement augmentation and have implications concerning the nature of the surgical procedures as well as the material used for injection.

Adult↗

Comparative evaluation of the osteoinductivity of two formulations of human demineralized bone matrix.

In the United States, demineralized bone matrix (DBM) is considered a transplantable tissue and therefore is regulated primarily by the American Association of Tissue Banks. Even though DBM is not subjected to the same regulations relative to performance claims as medical devices are, one would expect different processing methods might yield DBM preparations of different osteoinductive potential. The purpose of this study was to use an established athymic rat model to compare the osteoinductive properties of two commercially available human DBMs prepared using different methods but having essentially identical product claims. Sixteen female athymic rats were used to test equivalent volumes of two lots each of Grafton Putty (Osteotech, Inc., Eatontown, NJ), Osteofil (Regeneration Technologies, Inc., Alachua, FL), and rat DBM. At 28 days after implantation, qualitative and semiquantitative microscopy showed no significant differences in bone formation between the two lots from each source, but rat DBM produced significantly more bone than Grafton, which produced significantly more bone than Osteofil. Our results suggest that methods of graft processing may represent a greater source of variability than do differences among individual donors. Whether these differences relate to methods of demineralization, carrier, dose of DBM per volume, or to some other factor remains to be determined.

Animals↗

Histology of tissues within retrieved human titanium mesh cages.

STUDY DESIGN: Histologic documentation of contents within retrieved, failed human titanium mesh cages. OBJECTIVES: The purpose of this study is to describe the contents of a series of retrieved, clinically failed titanium mesh cages from human patients. SUMMARY OF BACKGROUND DATA: The use of interbody fusion cages is gaining rapid acceptance, but there is little histologic documentation of tissue within retrieved cages. METHODS: Eleven Titanium Surgical Mesh Cages (Harms; DePuy AcroMed, Raynham, MA) retrieved from 10 patients were histologically analyzed. Indications for cage retrieval included failed fusion or failed fusion with instrumentation failure. The cages had been in situ from 2 to 47 months. Histologic sections were reviewed qualitatively, and the approximate percent of area in the cage occupied by viable bone, necrotic bone, fibrocartilage, hyaline cartilage, fibrous tissue, and bone graft substitute was visually estimated. Particles of metal debris were estimated by a semiquantitative scoring system. RESULTS: All cages except one showed evidence of vascular ingrowth and areas of histologically viable bone, representing incorporating bone graft. At least a few particles of debris were present in 9 of 11 cages. Fibrocartilage of probable intervertebral disc origin ranged from 0% to 70% of the available area. Several cages contained small seams of fibrocartilage connecting segments of bone in a pattern that suggested a response to motion. CONCLUSIONS: Mean viable bone area within 11 retrieved, human titanium mesh cages was approximately 31%. Seams of fibrocartilage within the cages may represent tissue differentiation in response to bending or compressive load.

Adult↗

"Backside" polyethylene deformation in total knee arthroplasty.

The clinical importance of polyethylene deformation between the tibial insert and base plate ("backside") is unclear. We used a semiquantitative scoring system to compare clinical and radiographic factors with articular and backside deformation of 106 retrieved polyethylene tibial inserts. Backside deformation was associated with polyethylene thickness and type of locking mechanism. Deformation of the articular surface correlated with femoral osteolysis (P=.05). The mean backside deformation score was 33% greater for implants from patients with osteolysis than for implants from patients without osteolysis (P=.07). Our study may be biased based on the types of implants available for study, but for this group of implants, we cannot conclude with 95% certainty that backside polyethylene deformation was clinically important as a cause of periprosthetic osteolysis or implant loosening.

Adult↗

The effect of particle wear debris on NFkappaB activation and pro-inflammatory cytokine release in differentiated THP-1 cells.

Orthopedic wear debris has been thought to be an important factor associated with osteolysis and loosening of total joint arthroplasties. Previous in vitro studies have reported that particles of wear debris induce the release of pro-inflammatory cytokines and other inflammatory mediators from macrophages and other cells. Several recent investigations, however, have suggested that the wear particles themselves may not be primarily responsible for the inflammatory cellular responses, but that the observed cytokine release in vitro may be caused by endotoxin adsorbed to commercially available particle preparations. The intracellular pathways involved in macrophage signal transduction also are poorly understood. The purposes of this study are to use isolated orthopedic wear debris particles to evaluate pro-inflammatory cytokine release and nuclear factor kappa B (NFkappaB) activation from macrophages. Cells from human monocyte/macrophage cell line (THP-1) were differentiated and incubated with particles of debris that had been isolated from a failed human total hip arthroplasty. The titanium-alloy particles did not evoke release of TNF-alpha or IL-1beta whereas lipopolysaccharide (LPS) or LPS-treated debris particles induced both TNF-alpha and IL-1beta. LPS-treated particles, but not particles alone, stimulated NFkappaB activation. Our results suggest that at the concentrations tested in this study, endotoxin-free wear debris particles may not themselves initiate inflammatory cellular responses in differentiated THP-1 cells. It is unclear whether adsorbed endotoxin is clinically associated with osteolysis and/or loosening in total joint arthroplasties, but several factors, including adsorbed endotoxin, need to be investigated to explore the cellular responses responsible for osteolysis and/or loosening.

Arthroplasty, Replacement↗

Histologic and quantitative wear particle analyses of tissue around cementless ceramic total knee prostheses.

We histologically analyzed tissue biopsy specimens obtained from 4 cases of revised cementless ceramic knee prostheses. Particles were isolated from the specimens, and their size and composition were determined. Implants were removed for aseptic loosening at an average of 64 months. Histologically, polyethylene particles were seen in all cases. The concentration of the particles showed wide variation among cases. The concentration of the particles also showed a wide variation among different biopsy locations, suggesting that the particles were not distributed uniformly around the knee prostheses. Although we analyzed only 4 cases, our results show good correlation between radiographic evidence of geographic osteolysis and the concentration of wear particles. Multiple biopsy specimens may be necessary to characterize adequately particle migration around knee prostheses.

Aged↗

Bioactive materials in orthopaedic surgery: overview and regulatory considerations.

Although bone graft continues to be the standard against which other skeletal substitutes are measured, orthopaedic surgeons soon will have various new tools available for skeletal reconstruction. With these tools, the distinctions between inert materials, resorbables, bioactive materials, transplantable tissues, engineered tissues, drugs, and composites become indistinct. Although almost any implanted material evokes some type of host reaction, in the context of reconstructive orthopaedic surgery, bioactive materials can be considered osteogenic, osteoconductive, osteoinductive, or a combination thereof. In the United States, the regulatory control of a new skeletal substitute material is complex, and is based in part on whether the material is considered primarily a biologic, a drug, or a medical device. Different agencies within the Food and Drug Administration have responsibility for regulatory control of different types of products. Although some new materials can be approved by a Premarket Notification (510(K)), others require a Premarket Approval Application. Regulations are being developed that affect the extent of regulatory influence over minimally manipulated tissues for transplantation.

Bone Morphogenetic Proteins↗

Use of injectable calcium phosphate cement for fracture fixation: a review.

Injectable osteoconductive calcium phosphate cements have been introduced as an adjunct to internal fixation for treating selected fractures. These cements harden without producing much heat, develop compressive strength, and are remodeled slowly in vivo. The main purpose of the cement is to fill voids in metaphyseal bone, thereby reducing the need for bone graft, but cements also may improve the holding strength around metal devices in osteoporotic bone. Several bioactive cements are being developed. One of these cements, Skeletal Repair System, is available in Europe and has been approved by the United States Food and Drug Administration for use in selected distal radius fractures. Cadaveric studies have shown that using Skeletal Repair System cement with conventional metal fixation in certain fractures of the distal radius, tibial plateau, proximal femur, and calcaneus can produce better stability, stiffness, and strength than metal fixation alone. Early clinical results have shown reduced time to full weightbearing when cement has been used for augmentation of tibial plateau and calcaneal fractures, more rapid gain of strength and range of motion when used in distal radius fractures, and improved stability in certain hip fractures. Bioactive cements in general also may prove useful in vertebroplasty.

Animals↗

Demineralized bone matrix and native bone morphogenetic protein in orthopaedic surgery.

The recognition that demineralized bone matrix could induce bone formation when placed in mammalian skeletal muscle led to preclinical studies of crude native insoluble bone morphogenetic protein and noncollagenous protein, followed by the clinical application of demineralized bone matrix, chemosterilized autolyzed antigen-extracted allogenic bone, and autolyzed antigen-extracted allogenic bone matrix gelatin. Cultural norms and regulatory agencies influence the availability of different demineralized bone matrix preparations in different parts of the world, but there is continued interest in the biologic structure of native insoluble bone morphogenetic protein and noncollagenous protein aggregates and the applied science of osteoinduction and osteoconduction in reconstructive orthopaedic surgery. Demineralized bone matrix is not widely available in Asia, but tissue processing facilities in the United States distribute demineralized bone matrix materials with different carriers, handling properties, and possibly osteoinductive potential. The purpose of the current study was to review the development and use of various preparations of demineralized bone matrix materials.

Animals↗

Histologic evaluation of posterior cruciate ligaments from osteoarthritic knees.

It is controversial whether posterior cruciate ligament-retaining or posterior cruciate ligament-sacrificing (-substituting) implants should be used in total knee arthroplasty. The use of posterior cruciate ligament-retaining implants implies that the residual ligament is functional, and presumably normal, but few studies have been conducted to elucidate the histologic appearance of the posterior cruciate ligament taken from osteoarthritic knees. The purposes of the current study were (1) to evaluate the histologic appearance of posterior cruciate ligaments excised from osteoarthritic knees during primary total knee arthroplasty and to compare their appearance with posterior cruciate ligaments from knees of cadavers that were not operated on; and (2) to determine whether a correlation exists between the histologic appearance of the posterior cruciate ligament and the clinical status of the patients studied. Twenty-six posterior cruciate ligament specimens from patients with osteoarthritis and four specimens from cadavers were evaluated with the use of light and electron microscopy. Posterior cruciate ligaments from osteoarthritic knees showed greater degeneration than those from cadavers by light microscopy. Age greater than 60 years was associated with decreased collagen diameter in posterior cruciate ligaments from osteoarthritic knees as determined by electron microscopy. With the number of specimens available, the authors could not find a significant correlation between tibiofemoral alignment and mean collagen diameter or percentage of collagen occupancy. The extent of tissue degeneration of the posterior cruciate ligament could not be predicted by clinical findings. Additional studies identifying the mechanical competency of the posterior cruciate ligament in osteoarthritis would be valuable.

Adult↗

A multicenter retrieval study of the taper interfaces of modular hip prostheses.

A multicenter retrieval analysis of 231 modular hip implants was done to investigate the effects of material combination, metallurgic condition, flexural rigidity, head and neck moment arm, neck length, and implantation time on corrosion and fretting of modular taper surfaces. Scores for corrosion and fretting were assigned to medial, lateral, anterior, and posterior quadrants of the necks, and proximal and distal regions of the heads. Neck and head corrosion and fretting scores were found to be significantly higher for mixed alloy versus similar alloy couples. Moderate to severe corrosion was observed in 28% of the heads of similar alloy couples and 42% of the heads of mixed alloy couples. Differences in corrosion scores were observed between components made from the same base alloy, but of different metallurgic conditions. Corrosion and fretting scores tended to be higher for heads than necks. Implantation time and flexural rigidity of the neck were predictors of head and neck corrosion and head fretting. The results of this study suggest that in vivo corrosion of modular hip taper interfaces is attributable to a mechanically-assisted crevice corrosion process. Larger diameter necks will increase neck stiffness and may reduce fretting and subsequent corrosion of the taper interface regardless of the alloy used. Increasing neck diameter must be balanced, however, with the resulting loss of range of motion and joint stability.

Adult↗

Particles and periimplant bone resorption.

There is compelling evidence that the most important factor in late periprosthetic bone resorption is an inflammatory reaction to debris. Based on results from several laboratories, it seems likely that opsonized particles activate the macrophage nuclear factor-kappa B signal transduction system via membrane receptors, leading to release of tumor necrosis factor-alpha and other cytokines and growth factors. Tumor necrosis factor stimulates osteoblasts to release cytokines that recruit inflammatory cells and osteoclast precursors to the site and promote the differentiation of early osteoclasts. Tumor necrosis factor influences fibroblasts to release tissue metalloproteinases, and induces c-src in osteoclast precursors, the expression of which is necessary for additional bone resorption. Phagocytosis of debris by osteoblasts may reduce collagen synthesis, whereas phagocytosis by fibroblasts may induce chemokines that amplify inflammation. Bone has been partially protected from particle-induced resorption in animals with defective or inhibited tumor necrosis factor or nuclear factor-kappa B signaling. Many aspects of this inflammatory reaction require clarification, including identifying the factors that influence variability among patients, and testing the importance of costimulatory molecules such as bacterial endotoxin, but the fundamental importance of particles in most cases of aseptic loosening seems certain.

Animals↗