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Methods for modulating chondrocyte proliferation using pulsing electromagnetic fields

A cartilage and electrode technology, applied in electrotherapy, treatment, etc., can solve the problems of inability to provide signals, high price, large circuit complexity, and input power, and achieve the effect of promoting growth and repair, low cost, and lasting healing

Active Publication Date: 2008-08-06
HEALTHONICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Unfortunately, most electrotherapeutic devices available today rely on direct implantation of electrodes or entire electronics assemblies, or on inductive coupling through the skin using coils that generate time-varying magnetic fields, thereby Induces weak eddy currents, which do not effectively deliver said signal to the tissue, thus requiring a larger signal generator and battery pack in addition to bulky coils
The need for surgical and biocompatible materials on the one hand and excessive circuit complexity and input power on the other hand have made most such devices expensive and also limited their use to highly trained personnel

Method used

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  • Methods for modulating chondrocyte proliferation using pulsing electromagnetic fields
  • Methods for modulating chondrocyte proliferation using pulsing electromagnetic fields
  • Methods for modulating chondrocyte proliferation using pulsing electromagnetic fields

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0141] Effects of PEMF signaling structure on mineralization and morphology in primary osteoblast cultures

[0142] The goal of this study was to compare two PEMF waveform structures delivered by capacitive coupling by evaluating biochemical and morphological changes in primary osteocyte cultures.

[0143] method

[0144] Osteoblast culture: primary human osteoblasts (CAMBREX  , Walkersville, MD) was amplified to 75% confluence (confluence), and seeded directly on the previously described LAB-TEK at a density of 50,000 cells / ml TM (NALGENUNC INTERNATIONAL TM , Rochester, NY) room. Cultures were initially supported on basal osteoblast medium in the absence of differentiation factors. When the cultures reached 70% confluency in house, the medium was supplemented with hydrocortisone-21-hemisuccinate (200 mM final concentration), β-glycerophosphate (10 mM final concentration) and ascorbic acid. At 37°C, 5% CO 2 , Osteoblasts were cultured in humid air under 95% air for 21 d...

Embodiment 2

[0160] Use of niobium "salt" bridges for PEMF stimulation in vitro

[0161] introduction

[0162] Development of passive electrode systems using anodized niobium wires to couple time-varying electrical signals into the culture chamber. The purpose of this design is to replace the traditional electrolyte used to transmit PEMF-like signals (such as those generated capacitively rather than inductively by the EBI repetitive pulse segment bone growth stimulator in in vitro tissue for cell and tissue research). bridge technology to reduce complexity and improve reproducibility. Anodized niobium wire is readily available and requires only simple hand tools to form the electrode bridge. At the available frequencies (typically between 5Hz and 3Hz), the passage of DC current is negligible.

[0163] background

[0164] Capacitively coupled electric fields have generally been introduced into culture media with traditional electrolyte salt bridges, which have limited frequency response...

Embodiment 3

[0174] Stimulation of chondrocytes using capacitively coupled PEMF signals

[0175] introduction

[0176] Clinical applications of PEMF signaling similar to those used for bone repair are currently being tested for their ability to reduce joint pain in arthritic patients. Of interest is whether this pain-reducing signal can also ameliorate the underlying problem of damaged cartilage.

[0177] background

[0178] Compared to drug treatments and biologics, PEMF-based therapeutics offer an easy-to-use non-invasive treatment that contains no foreign agents with potential side effects and has zero washout time. Problems with PEMF therapeutic approaches include: identifying responding cells, elucidating the physical transduction site on the cell, and determining the biological mechanism of the response leading to the cellular response. The purpose of this study was to determine whether the specific PEMF signal currently being tested for pain reduction (MEDRELIEF(R), Healthonics, ...

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Abstract

The present invention provides compositions and methods for modulating the growth, development, and repair of bone, cartilage, or other connective tissue. Also provided are devices and stimulation waveforms to differentially modulate the behavior of osteoblasts, chondrocytes, and other connective tissue cells to promote proliferation, differentiation, matrix formation, or mineralization for in vitro or in vivo applications. Continuous mode and pulsed segment mode of cell stimulation with charge-balanced signals can be used. Bone, cartilage, and other connective tissue growth is stimulated in part by the release of nitric oxide via electrical stimulation, and can be regulated by simultaneous supply of NO donors and NO synthase inhibitors. Bone, cartilage and other connective tissue growth is stimulated in part by the release of BMP-2 and BMP-7 in response to electrical stimulation that promotes cell differentiation. The methods and devices are useful for promoting bone fracture repair, cartilage and connective tissue repair, and for engineering tissue for transplantation.

Description

[0001] Cross application of related applications [0002] This application claims U.S. Provisional Patent Application 60 / 687,430, filed June 3, 2005, U.S. Provisional Patent Application 60 / 693,490, filed June 23, 2005, U.S. Provisional Patent Application 60 / 782,462, filed March 15, 2006 and priority of US Provisional Patent Application 60 / 790,128, filed April 7, 2006. Background technique [0003] Diseases and injuries associated with bone and cartilage have a large impact on the human population. Approximately 5 million fractures occur each year in the United States alone. About 10% of these have delayed union, and of these, 150,000 to 200,000 nonunion fractures occur with loss of productivity and independence. In the case of cartilage, severe chronic forms of knee cartilage damage can lead to greater deterioration of the articular cartilage and may eventually lead to replacement of the entire knee joint. Each year, approximately 200,000 total knee replacement surgeries ar...

Claims

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Application Information

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IPC IPC(8): A61N1/00
Inventor J・W・科隆博格T・甘尼S・L・戈尔顿
Owner HEALTHONICS INC
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