Carl T Brighton
University of Pennsylvania · Rehabilitation Medicine
Active 1965–2014
About
Carl T Brighton is a faculty member in the Department of Orthopaedic Surgery at the Perelman School of Medicine at the University of Pennsylvania. His contact information includes an office located at G08A Stemmler Hall, 3550 Market St, Suite 220, Philadelphia, PA 19104, with an office phone number of 215-898-8653 and an email address at ctb@mail.med.upenn.edu. The biography indicates his association with the university's medical school and his role within the orthopaedic surgery department, but does not provide further details about his research focus, background, or key contributions.
Research topics
- Medicine
- Chemistry
- Anatomy
- Surgery
- Cell biology
Selected publications
Journal of Orthopaedic Research® · 2014-03-18 · 59 citations
articleOpen accessSenior authorCorrespondingThe objective of the described experiments was to determine the electrical parameters that lead to optimal expression of a number of bone-related genes in cultured human bone cells exposed to a capacitively coupled electric field. Human calvarial osteoblasts were grown in modified plastic Cooper dishes in which the cells could be exposed to various capacitively coupled electric fields. The optimal duration of stimulation and optimal duration of response to the electrical field, and the optimal amplitude, frequency and duty cycle were all determined for each of the genes analyzed. Results indicated that a capacitively coupled electric field of 60 kHz, 20 mV/cm, 50% duty cycle for 2 h duration per day significantly up-regulated mRNA expression of a number of transforming growth factor (TGF)-β family genes (bone morphogenetic proteins (BMP)-2 and -4, TGF-β1, - β2 and -β3) as well as fibroblast growth factor (FGF)-2, osteocalcin (BGP) and alkaline phosphatase (ALP). Protein levels of BMP-2 and -4, and TGF-β1 and - β2 were also elevated. The clinical relevance of these findings in the context of a noninvasive treatment modality for delayed union and nonunion fracture healing is discussed.
Open Journal of Biophysics · 2013-01-01 · 5 citations
articleOpen access1st authorCorrespondingWe have previously shown that capacitively coupled electrical stimulation of either normal bovine articular chondrocytes or osteoarthritic human articular cartilage explants resulted in up-regulation of cartilage matrix gene expression and down-regulation of metalloproteinase gene expression. In addition, collagen and proteoglycan protein levels were also elevated. To determine visually the effect of specific electric fields on modifying cartilage structure, freshly harvested human full-thickness osteoarthritic cartilage explants were stimulated in the absence or presence of interleukin-1β, an inflammatory cytokine, and were examined photographically and spectrophotometrically. Hexosamine and hydroxyproline contents were also determined. Spectrophotometric analysis was used to quantify any changes in the depth of defects in the cartilage ranging from surface level (red-colored) to the deepest affected layer (blue-colored). Interleukin-1β treatment alone caused significant additional cartilage erosion. Electrical stimulation alone resulted in significant decreases in the cartilage defects. Electrical stimulation in the presence of interleukin-1β resulted in a small, but significant, surface improvement. Meta-analysis also confirmed a significant increase in the hexosamine and hydroxyproline contents (indicating matrix deposition). It was concluded that an appropriate electric field could modify osteoarthritic lesions in full-thickness cartilage plugs by increasing matrix production and/or by decreasing matrix destruction. Furthermore, it appears that spectrophotometric analysis is a relatively easy method for quantifying the “filling in” or healing of articular cartilage defects.
Journal of Bone and Joint Surgery · 2008-04-01 · 100 citations
article1st authorCorrespondingBACKGROUND: The destruction of cartilage in patients with osteoarthritis is a consequence of an imbalance between matrix synthesis and degradation. The purpose of the present study was to determine the effects of electrical stimulation on these processes in full-thickness osteoarthritic adult human articular cartilage explants. METHODS: Full-thickness articular cartilage explants from osteoarthritic adult human knee joints were cultured in the absence or presence of interleukin-1beta (IL-1beta) and in the absence or presence of a specifically defined capacitively coupled electrical signal for seven or fourteen days. Total collagen and proteoglycan production were assessed by means of hydroxyproline and hexosamine analyses, respectively. Quantitative real-time polymerase chain reaction assays were used to measure mRNA expression levels of aggrecan, type-II collagen, collagenase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), aggrecanase-1 (ADAM-TS4), and aggrecanase-2 (ADAM-TS5). RESULTS: Electrical stimulation of cultured explants for seven or fourteen days resulted in significant increases (p < 0.007) in proteoglycan and collagen production and a highly significant upregulation (p <or= 0.005) of aggrecan and type-II collagen mRNA expression. This occurred even in the presence of IL-1beta. In the absence of IL-1beta, the expression of metalloproteinases was at barely detectable levels in these explants. Treatment with IL-1beta led to the significant upregulation of metalloproteinase expression (p < 0.03), but simultaneous administration of the capacitively coupled electrical signal dramatically inhibited this stimulation. CONCLUSIONS: The data show that, even in the presence of IL-1beta, a specific, defined capacitively coupled electrical signal can result in significant upregulation of cartilage matrix protein expression and production while simultaneously significantly attenuating the upregulation of metalloproteinase expression. These results support the contention that delivery of a specific, defined electrical field to articular cartilage could result in matrix preservation.
Osteoarthritis and Cartilage · 2008-11-11 · 123 citations
articleOpen accessSenior authorJournal of Bone and Joint Surgery · 2006-05-01 · 108 citations
articleSenior authorBackground: Capacitively coupled electric stimulation has been successfully used in the treatment of bone nonunions and to effect spinal fusions. However, the pathway of biologic events whereby this is accomplished has not been fully elucidated. To determine whether bone morphogenetic proteins (BMPs) could be involved, the effect of electrical stimulation on BMP gene expression was investigated. Methods: Postconfluent cultures of MC3T3-E1 bone cells were exposed to a series of capacitively coupled signals in which the duration, amplitude, frequency, and duty cycle were sequentially and systematically varied. The cellular response was measured by quantifying the mRNA levels of BMP-2 through BMP-8, as well as the BMP antagonists gremlin and noggin, with use of reverse transcription followed by real-time quantitative polymerase chain reaction. BMP-2 protein was measured by enzyme-linked immunosorbent assay, and alkaline phosphatase activity was measured by a specific colorimetric assay. Results: The results showed that BMP-2 through BMP-8, gremlin, and noggin were all normally expressed by MC3T3-E1 cells, and could be significantly up-regulated by specific and selective capacitively coupled electric fields (p < 0.05). However, mRNA expression for BMP-2, 4, 5, 6, and 7 was consistently up-regulated several times higher than that for BMP-3 and BMP-8, gremlin, and noggin under identical conditions. Concomitantly, BMP-2 protein production and alkaline phosphatase activity were both significantly increased in the same electrically stimulated cultures (p = 0.001 and p < 0.01, respectively). Conclusions: These data clearly show that our optimal capacitively coupled signal (60 kHz, 20 mV/cm at a 50% duty cycle for twenty-four hours) can specifically, selectively, and simultaneously up-regulate the expression of a number of osteoinductive BMPs; other BMPs and antagonists are only moderately affected. Clinical Relevance: Electrical stimulation may be a useful treatment modality for in vivo situations where bone induction is required, since it is noninvasive, safe, effective, can be easily targeted to a variety of anatomic sites, can provide a controlled production of BMPs, and can be used repeatedly. The optimal duration (continuous stimulation at 100% duty cycle) and frequency (60 kHz) determined in this in vitro study are the same—and the amplitude (20 mV/cm) is in the same range (12 mV/cm)—as are used clinically.
The Required Research Rotation in Residency
Clinical Orthopaedics and Related Research · 2006-06-01 · 27 citations
articleSenior authorThe University of Pennsylvania orthopaedic surgery residency program under the direction of Dr. Carl T. Brighton was uniquely structured to require a year of research as part of a 5-year program. This requirement was instituted to foster critical thinking, and not necessarily to produce academic orthopaedic surgeons. Nonetheless, measures of academic productivity of the 127 residents who trained under Dr. Brighton's leadership may be instructive. The purpose of this study was to assess metrics of academic productivity. In addition, the six current and former chairmen of orthopaedic surgery programs who performed research while residents at the University of Pennsylvania were surveyed for their impressions regarding required research rotations. Fifty-nine percent of the University of Pennsylvania residents took faculty positions after training; 75% published a peer-reviewed paper after residency; and 17% are current members of the American Orthopaedic Association. Overall, the chairmen surveyed found great value in their own resident research experience, but none have replicated the Brighton model of residency organization. Only two of the six programs have a research year: at both, this research rotation is in addition to the standard 5 years of clinical education and only at one are all residents required to participate.
Journal of Bone and Joint Surgery · 2006-05-01 · 18 citations
articleSenior authorBackground: Capacitively coupled electric stimulation has been successfully used in the treatment of bone nonunions and to effect spinal fusions. However, the pathway of biologic events whereby this is accomplished has not been fully elucidated. To determine whether bone morphogenetic proteins (BMPs) could be involved, the effect of electrical stimulation on BMP gene expression was investigated. Methods: Postconfluent cultures of MC3T3-E1 bone cells were exposed to a series of capacitively coupled signals in which the duration, amplitude, frequency, and duty cycle were sequentially and systematically varied. The cellular response was measured by quantifying the mRNA levels of BMP-2 through BMP-8, as well as the BMP antagonists gremlin and noggin, with use of reverse transcription followed by real-time quantitative polymerase chain reaction. BMP-2 protein was measured by enzyme-linked immunosorbent assay, and alkaline phosphatase activity was measured by a specific colorimetric assay. Results: The results showed that BMP-2 through BMP-8, gremlin, and noggin were all normally expressed by MC3T3-E1 cells, and could be significantly up-regulated by specific and selective capacitively coupled electric fields (p < 0.05). However, mRNA expression for BMP-2, 4, 5, 6, and 7 was consistently up-regulated several times higher than that for BMP-3 and BMP-8, gremlin, and noggin under identical conditions. Concomitantly, BMP-2 protein production and alkaline phosphatase activity were both significantly increased in the same electrically stimulated cultures (p = 0.001 and p < 0.01, respectively). Conclusions: These data clearly show that our optimal capacitively coupled signal (60 kHz, 20 mV/cm at a 50% duty cycle for twenty-four hours) can specifically, selectively, and simultaneously up-regulate the expression of a number of osteoinductive BMPs; other BMPs and antagonists are only moderately affected. Clinical Relevance: Electrical stimulation may be a useful treatment modality for in vivo situations where bone induction is required, since it is noninvasive, safe, effective, can be easily targeted to a variety of anatomic sites, can provide a controlled production of BMPs, and can be used repeatedly. The optimal duration (continuous stimulation at 100% duty cycle) and frequency (60 kHz) determined in this in vitro study are the same—and the amplitude (20 mV/cm) is in the same range (12 mV/cm)—as are used clinically.
Up-regulation of matrix in bovine articular cartilage explants by electric fields
Biochemical and Biophysical Research Communications · 2006-02-10 · 52 citations
article1st authorCorrespondingMeasurement of power delivery system impedance, current and switching activity on functioning die
2005-08-30 · 3 citations
articlePower delivery system (PDS) noise, current and impedance are major indicators of chip performance. The paper considers an approach in which on-chip impedance measurement is conducted for controlled periodic step-wise computer process. The main difficulty of the approach is current reconstruction. Current can be obtained from measured equivalent conductance of the chip, which can serve as a quantification of chip activity.
Up-regulation of Chondrocyte Matrix Genes and Products by Electric Fields
Clinical Orthopaedics and Related Research · 2004-10-01 · 76 citations
articleSenior authorCorrespondingThis study tested the hypothesis that selective and specific capacitively coupled electrical signals could stimulate gene expression and matrix production in bovine articular chondrocytes. Starting with a capacitively coupled electric signal that previously was shown to be effective in stimulating proliferation in bovine articular cartilage chondrocytes, dose responses were done sequentially for duration, response time, amplitude, duty cycle, and frequency. Results showed that a 0.5-hour, 20 mV/cm, signal at 60 kHz up-regulated aggrecan gene expression approximately eightfold (p < 0.0003) using a 50% duty cycle, whereas Type II collagen gene expression was up-regulated approximately fivefold (p < 0.02) using an 8.3% duty cycle. Using a compound signal (a 0.5-hour continuous period plus multiple 1-hour periods of 50% duty cycle for 7 days) both proteoglycan and collagen accumulation in vitro were increased approximately fivefold (p < 0.0003) and twofold (p < 0.0008), respectively. Also, the most effective capacitively coupled electric signal was different for each of the two molecules studied (aggrecan, 50% duty cycle and 4-hour response time; Type II collagen, 8.3% duty cycle and 6-hour response time). We conclude that selective up-regulation of gene expression and matrix accumulation of cartilage structural macromolecules (such as aggrecan and Type II collagen) with specific capacitively coupled fields occurs in vitro. This may be useful in vivo as a noninvasive modality to promote cartilage healing or ameliorate the effects of osteoarthritis, or both.
Recent grants
NIH · $146k · 1988
NIH · $187k · 1987
NIH · $1.5M · 1994
NIH · $2.2M · 1997
NIH · $197k · 1987
Frequent coauthors
- 30 shared
Solomon R. Pollack
University of Pennsylvania
- 26 shared
Frederick S. Kaplan
University of Pennsylvania
- 21 shared
Joseph M. Lane
- 21 shared
Zachary B. Friedenberg
NewYork–Presbyterian Hospital
- 20 shared
R. Bruce Heppenstall
- 20 shared
John L. Esterhai
- 16 shared
Jonathan Black
- 15 shared
Robert M. Hunt
Federal Reserve Bank of Philadelphia
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