Chemistry: molecular biology and microbiology – Condition responsive control process
Reexamination Certificate
2000-07-06
2001-10-16
Redding, David A. (Department: 1744)
Chemistry: molecular biology and microbiology
Condition responsive control process
C435S173100, C073S781000, C073S788000, C073S805000
Reexamination Certificate
active
06303286
ABSTRACT:
TECHNICAL FIELD
This invention relates to a system and method for providing adaptive control of the stimulation of a muscle tissue specimen in order to emulate its in vivo environment.
BACKGROUND ART
At present, three-dimensional tissues are capable of being produced in vitro using various types of cells. For example, U.S. Pat. No. 5,443,950 issued to Naughton et al. describes three-dimensional cultures for bone marrow, skin, liver, vascular, and pancreatic tissues which are grown within synthetic matrices. In these tissues as well as others, investigators have been successful in proliferating cells and tissues in vitro such that the resulting three-dimensional tissues, termed “organoids” or “constructs”, display many of the characteristics of their in vivo counterparts. These constructs have a variety of foreseeable applications, ranging from transplantation in vivo to functional and pharmacological testing in vitro.
In the case of skeletal muscle constructs grown in vitro, the cells generally remain in a developmentally arrested state. To maximize the usefulness of skeletal muscle constructs for basic research, clinical diagnostic applications, and pharmaceutical screening, it would be desirable to promote and control the development of the constructs, in particular the induction of full differentiation of the muscle fibers, such that the constructs more closely mimic their in vivo counterparts.
To this end, the scientific literature indicates that interventions such as the application of controlled mechanical strain and transverse electrical fields are involved in the promotion of the correct orientation and differentiation of skeletal muscle cells in culture. Applying this knowledge, there are systems that allow the application of different mechanical strain patterns to cells in culture. See, for example, U.S. Pat. Nos. 4,940,853 and 5,153,136 issued to Vandenburgh.
However, these existing cell culture systems have several deficiencies. First, the systems focus on only one type of intervention, namely the application of mechanical strain. Furthermore, the systems are not capable of readily evaluating the contractile function of skeletal muscle constructs in vitro. Without the capability to detect tissue function or properties, present systems are forced to employ preprogrammed, open-loop control of strain parameters, and therefore are not able to knowledgeably adapt the strain parameters to changes in the development of individual tissue samples.
DISCLOSURE OF INVENTION
Therefore, it is an object of the present invention to provide a system and method for adaptively controlling the stimulation of a muscle tissue specimen in order to emulate its in vivo environment.
It is another object of the present invention to provide a system and method capable of integrating and applying multiple types of stimuli to a muscle tissue specimen to emulate its in vivo environment.
It is still another object of the present invention to provide a system and method for continuously monitoring the response of a muscle tissue specimen to stimulation.
Accordingly, a method is provided for emulating an in vivo environment of a muscle tissue specimen. The method includes stimulating the muscle tissue specimen based on an initial control signal. The method further includes generating a response signal based on a response of the muscle tissue specimen to the step of stimulating. In addition, the method includes modifying the initial control signal based on the response signal to obtain a final control signal, wherein the final control signal is used to elicit a desired response from the muscle tissue specimen.
To carry out the method of the present invention, a system is provided for emulating an in vivo environment of a muscle tissue specimen. The system includes at least one stimulator operable to apply stimulation to the muscle tissue specimen based on an initial control signal. The system additionally includes means for generating a response signal based on a response of the muscle tissue specimen to the stimulation. Further, the system includes a controller capable of modifying the initial control signal based on the response signal to obtain a final control signal, wherein the final control signal is used to elicit a desired response from the muscle tissue specimen.
The stimulation preferably includes electrical or mechanical stimulation. Most preferably, these different types of stimulation can be applied simultaneously. In a preferred embodiment, the generating means includes a force transducer, and electrical and mechanical stimulation are provided by an electrical stimulator and a servomotor, respectively. The response signal preferably represents force production of the muscle tissue specimen. Advantageously, the system and method of the present invention can be used to adaptively control the stimulation of a muscle tissue specimen in a tissue culture environment.
The above objects and other objects, features, and advantages of the present invention are more readily understood from a review of the attached drawings and the accompanying specification and claims.
REFERENCES:
patent: 4605623 (1986-08-01), Malette et al.
patent: 4940853 (1990-07-01), Vandenburg et al.
patent: 5153136 (1992-10-01), Vandenburg
patent: 5443950 (1995-08-01), Naughton et al.
patent: 5452236 (1995-09-01), Lintilhac et al.
patent: 5618718 (1997-04-01), Auger et al.
patent: 5700688 (1997-12-01), Lee et al.
patent: 5882929 (1999-03-01), Fofonoff et al.
Herman A. Vandenburg et al., Skeletal Muscle Growth is Stimulated by Intermittent Stretch-Relaxtion In Tissue Culture, The American Physiological Society, 1989, pp. C674-682.*
Herman A. Vandenburg, In Vitro Cellular & Developmental Biology, vol. 24, No. 7, Jul., 1998, pp. 609-619.*
Herman A. Vandenburg et al. In Vitro Cellular & Developmental Biology, vol. 25, No. 7, 1989, pp. 607-616.*
Shansky et al. In Vitro Cellular & Developmental Biology, Oct. 1997. pp. 659-661.*
Herman A. Vandenburg et al., The FASEB Journal, vol. 5, Oct. 1991, pp. 2860-2867.*
Herman A. Vandenburg et al., Human Gene Therapy (Nov. 10, 1996), pp. 2195-2200.
Dennis Robert G.
Kosnik Paul
Brooks & Kushman P.C.
Redding David A.
The Regents of the University of Michigan
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