University of Pennsylvania

Biolectron, Inc.

Zimmer Gmbh

Bongenix, LLC

Carl T Brighton

Solomon R Pollack

Jonathan Black

Neil J Griffith

Joyce K Eyerly

Michael D Carlozzi

David Pienkowski

William Redka

A bone stimulating method and device for treating injured or diseased bone tissue, includes exposing the injured or diseased bone tissue to a first electric field over a predetermined treatment period, the first electric field ranging from 10 mV/cm to 40 mV/cm and having a first predetermined time period within the predetermined treatment period and exposing the injured or diseased bone tissue to a second electric field over the predetermined treatment period, the second electric field ranging from 10 mV/cm to 60 mV/cm and having a second predetermined time period within the predetermined treatment period that is greater than the first predetermined time period. The first electric field is specific and selective for up-regulating expression of specific bone cell genes in the injured or diseased bone tissue when the injured or diseased bone tissue containing the specific bone cell genes is exposed to the first electric field and the second electric field is specific and selective for up-regulating expression of specific bone stem cell genes in the injured or diseased bone tissue when the injured or diseased bone tissue containing the specific bone stem cell genes is exposed to the second electric field.

Method and device for stimulating bone growth

Methods and devices are described for the regulation of BMP 2 and 4, TGF-beta 1, 2, and 3, FGF-2, osteocalcin, and alkaline phosphatase mRNA in stem cells via capacitive coupling or inductive coupling of specific and selective electric and/or electromagnetic fields to the bone cells or other tissues containing the stem cells, where the specific and selective fields are generated by application of specific and selective signals to field generating devices disposed with respect to the stem cells so as to facilitate the treatment of diseased or injured bone and other tissues. The resulting methods and devices are useful for the targeted treatment of osteoporosis, osteopenia, osteonecrosis, fresh bone fractures, fractures at risk, nonunion, bone defects, spine fusion, and/or other conditions in which BMP 2 and 4, TGF-beta 1, 2, and 3, FGF-2, osteocalcin, and alkaline phosphatase mRNA and/or protein deficiencies in stem cells has been implicated.

Regulation of stem cell gene production with specific and selective electric and electromagnetic fields

Methods and devices for the regulation of gene expression by cells via the application of fields generated by specific and selective electric and electromagnetic signals so as to target diseased or injured tissue for treatment. By gene expression is meant the up regulation or down regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased tissue that include providing specific and selective electric and electromagnetic signals and exposing tissue to the fields generated by the signals so as to regulate gene expression. In particular, methods and devices are provided for the targeted treatment of bone defects, osteoarthritis, osteoporosis, cancer, and other disease states.

Regulation of genes via application of specific and selective electrical and electromagnetic signals

Methods and devices are described for the regulation of bone morphogenetic protein gene expression in bone cells via the application of fields generated by specific and selective electric and electromagnetic signals in the treatment of diseased or injured bone. By gene expression is meant the up-regulation or down-regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased bone tissue that include generating specific and selective electric and electromagnetic signals that generate fields optimized for increase of bone morphogenetic protein gene expression and exposing bone to the fields generated by specific and selective signals so as to regulate bone morphogenetic protein gene expression in such bone tissue. The resulting methods and devices are useful for the targeted treatment of bone fractures, fractures at risk, delayed unions, nonunion of fractures, bone defects, spine fusions, osteonecrosis or avascular necrosis, as an adjunct to other therapies in the treatment of one or all of the above, and in the treatment of osteoporosis.

System and method of up-regulating bone morphogenetic proteins (BMP) gene expression in bone cells via the application of fields generated by specific and selective electric and electromagnetic signals

Methods and devices are described for the regulation of Fibroblastic Growth Factor-2 mRNA and/or FGF-2 protein in bone cells and other tissues via capacitive coupling or inductive coupling of specific and selective electric and/or electromagnetic fields to the bone cells or other tissues, where the specific and selective fields are generated by application of specific and selective signals to electrodes or one or more coils or other field generating device disposed with respect to the bone cells or other tissues so as to facilitate the treatment of diseased or injured bone and other tissues. By gene expression is meant the up-regulation or down-regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased bone and other tissue that include generating specific and selective signals that generate electric and/or electromagnetic fields in the target tissue optimized for increase of FGF-2 protein gene expression and exposing bone and other tissue to the fields generated by specific and selective signals so as to regulate FGF-2 protein gene expression in such tissue. The resulting methods and devices are useful for the targeted treatment of osteoporosis, osteopenia, osteonecrosis, fresh bone fractures, fractures at risk, nonunion, bone defects, spine fusion, and/or other conditions in which FGF-2 protein has been implicated.

Regulation of fibroblastic growth factor-2 (FGF-2) gene expression in living cells with the application of specific and selective electric and electromagnetic fields

Methods and devices for the regulation of type II collagen gene expression in cartilage cells via the application of specific and selective fields generated by specific and selective electric and electromagnetic signals in the treatment of diseased or injured articular cartilage. By gene expression is meant the up regulation or down regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased cartilage tissue that include generating specific and selective electric and electromagnetic signals that generate specific and selective fields optimized for type II collagen gene expression and exposing cartilage tissue to the specific and selective fields generated by specific and selective signals so as to regulate type II collagen gene expression in such cartilage tissue. The resulting methods and devices are useful for the targeted treatment of osteoarthritis, rheumatoid arthritis, cartilage injury, and cartilage defects.

Regulation of type II collagen gene expression using specific and selective electrical and electromagnetic signals

A method of determining the voltage and current output required for the application of specific and selective electric and electromagnetic signals to diseased articular cartilage in the treatment of osteoarthritis, cartilage defects due to trauma or sports injury, or used as an adjunct with other therapies (cell transplantation, tissue-engineered scaffolds, growth factors, etc.) for treating cartilage defects in the human knee joint and a device for delivering such signals to a patient's knee. An analytical model of the human knee is developed whereby the total tissue volume in the human knee may be determined for comparison to the total tissue volume of the diseased tissue in the animal model using electric field and current density histograms. The voltage and current output used in the animal model is scaled based on the ratio of the total tissue volume of the diseased tissue of the human to the total tissue volume of the diseased tissue in the animal model and the resulting field is applied to the diseased tissue of the human using at least two electrodes applied to the knee or a coil or solenoid placed around the knee. The voltage of the signal applied to the electrodes, coil or solenoid is varied based on the size of the knee joint; larger knee joints require larger voltages to generate the effective electric field.

Method and device for treating osteoarthritis, cartilage disease, defects and injuries in the human knee

Methods and devices are described for the regulation of Transforming Growth actor (TGF)-&#x3b2;1, &#x3b2;2, and/or &#x3b2;3 protein gene expression in bone cells and other tissues via the capacitive coupling or inductive coupling of specific and selective electric fields to the bone cells or other tissues, where the specific and selective electric fields are generated by application of specific and selective electric and electromagnetic signals to electrodes or one or more coils or other field generating device disposed with respect to the bone cells or other tissues so as to facilitate the treatment of diseased or injured bone and other tissues. By gene expression is meant the up-regulation or down-regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased bone and other tissue that include generating specific and selective electric and electromagnetic signals that generate fields in the target tissue optimized for increase of TGF-&#x3b2;1, &#x3b2;2, and/or &#x3b2;3 protein gene expression and exposing bone and other tissue to the fields generated by specific and selective signals so as to regulate TGF-&#x3b2;1, &#x3b2;2, and/or &#x3b2;3 protein gene expression in such tissue. The resulting methods and devices are useful for the targeted treatment of bone fractures, fractures at risk, delayed unions, nonunion of fractures, bone defects, spine fusions, osteonecrosis or avascular necrosis, as an adjunct to other therapies in the treatment of one or all of the above, in the treatment of osteoporosis, and in other conditions in which TGF-&#x3b2;1, &#x3b2;2, and/or &#x3b2;3 protein may be implicated.

Regulation of transforming growth factor-beta (TGF-&#x3b2;) gene expression in living cells via the application of specific and selective electric and electromagnetic fields

Methods and devices for the regulation of matrix metalloproteinase gene expression in cartilage cells via the application of fields generated by specific and selective electric and electromagnetic signals in the treatment of diseased or injured articular cartilage. By gene expression is meant the up-regulation or down-regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased cartilage tissue that include generating specific and selective electric and electromagnetic signals that generate fields optimized for reduction of matrix metalloproteinase gene expression and exposing cartilage tissue to the fields generated by specific and selective signals so as to regulate matrix metalloproteinase gene expression in such cartilage tissue. The resulting methods and devices are useful for the targeted treatment of osteoarthritis, rheumatoid arthritis, cartilage injury, cartilage defects, and tumor metastasis.

Regulation of matrix metalloproteinase gene expression using specific and selective electrical and electromagnetic signals

Methods and devices for the regulation of aggrecan gene expression in cartilage cells via the application of fields generated by specific and selective electric and electromagnetic signals in the treatment of diseased or injured articular cartilage. By gene expression is meant the up regulation or down regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased cartilage tissue that include generating specific and selective electric and electromagnetic signals that generate fields optimized for aggrecan gene expression and exposing cartilage tissue to the fields generated by specific and selective signals so as to regulate aggrecan gene expression in such cartilage tissue. The resulting methods and devices are useful for the targeted treatment of osteoarthritis, rheumatoid arthritis, cartilage injury, and cartilage defects.

Regulation of aggrecan gene expression using specific and selective electrical and electromagnetic signals

A method for applying therapeutic electrical signals and/or electromagnetic fields to a patient's knee for the treatment of osteoarthritis and other diseases, defects and injuries. The device that is used is operable in several modes to deliver signals to the patients knee so as to cause an electric and/or electromagnetic field to be generated that selectively up-regulates gene expression of Aggrecan and Type II Collagen while simultaneously selectively down-regulating the gene expression of metalloproteases. The device includes a signal generator that generates compound electric signals including a 60 kHz sine wave having a peak to peak voltage of approximately 4.6 V to 7.6 V and a 100% duty cycle signal that is generated for approximately 30 minutes and a 50% duty cycle signal that is generated for approximately 1 hour after the 100% duty cycle signal. These compound electric signals are communicated to electrodes or coils in the proximity of a patient's knee for the generation of a specific and selective electromagnetic field that treats the diseased tissue.

Method for treating osteoarthritis and other diseases, defects and injuries of the knee joint

A method of determining the voltage and current required for the application of specific and selective electric and electromagnetic signals to diseased articular cartilage in the treatment of osteoarthritis, cartilage defects due to trauma or sports injury, or used as an adjunct with other therapies (cell transplantation, tissue-engineered scaffold, growth factors, etc.) for treating cartilage defects in the human hip joint and a device for delivering such signals to a patient's hip. Anatomic, analytical, and planar circuit models are developed to determining the impedances, conductivities, and current flows in the human hip joint and its surrounding soft tissues and skin that are required to produce a 20 mV/cm electric field in the synovium and articular cartilage of the human hip. The voltage of the signal applied to the surface electrodes or to a coil(s) or solenoid is varied based on the size of the hip joint; larger hip joints require larger voltages to generate the effective electric field.

Method and device for treating osteoarthritis and cartilage disease, defects, and injuries in the human hip

A technique and associated device for stimulating multiple electrodes with multiple electrical signals in multiple regions of the spine without injury to the patient. The electrodes are applied to respective sides of the patient's spine, and a first electrical signal is applied to any electrodes in a treatment area of the lumbar region of the patient's spine, a second electrical signal is applied to any electrodes in a treatment area of the thoracic region of the patient's spine, and a third electrical signal is applied to any electrodes in a treatment area of the cervical region of the patient's spine to induce osteogenesis in at least one of the respective treated area's of the patient's spine. The first, second, and third electrical signals respectively generate different electrode currents in the respective treated areas and are ideally selected to create current densities that are approximately equal in respective treatment areas. The electrodes may include electrode pairs or strip electrodes placed either side of the patient's spine in the respective treatment areas.

Device and method for electrically inducing osteogenesis in the spine

A technique and device for preventing and/or treating osteoporosis, hip and spine fractures, and/or spine fusions by incorporating at least one conductive coil () into a garment () adapted to be worn adjacent to the patient's skin over a treatment area and applying an electrical signal to the coil effective to produce a magnetic flux the penetrates the treatment area so as to produce an electric field in the bones and the treatment area.

Growing community of inventors

Malvern, PA, United States of America

Carl T Brighton