In-vitro mechanical loading of musculoskeletal tissues

Abstract

Musculoskeletal tissues produced in vitro are optimized in response to an externally applied mechanical load. The load applied may vary from tissue to tissue, depending upon the response desired, and may include intermittent axial, torsional, and bending loads to produce cortical structures. Compression alone is preferably applied to produce cancellous bone. A method according to the invention for culturing bone in vitro comprises: providing a culture vessel providing a scaffold material, supporting the scaffold material within the tissue culture vessel so as to be exposed to a tissue culture medium, and exerting a force on the scaffold material during growth of a bone construct (a cultured bone growth) around the scaffold material. Applicable apparatus preferably includes a culture vessel, holders for holding a scaffold within the tissue culture vessel, means for introducing a tissue culture medium to the tissue culture vessel, and an actuator adapted to apply a force to developing bone during the in vitro culture of the tissue, whether bone, cartilage, ligament, or composites thereof.

1 . A method of synthesizing musculoskeletal tissue, the method comprising the steps of:
 providing a cell culture vessel containing a cell culture medium;   introducing at least one musculoskeletal precursor to the medium;   applying a force to the musculoskeletal precursor in vitro through an actuator that mimics forces experienced by a bone in a body,   whereby the precursor develops into a musculoskeletal tissue matrix having desired properties through the application of the force.   
   
   
       2 . The method of  claim 1 , wherein the culture medium includes osteoblasts. 
   
   
       3 . The method of  claim 1 , wherein the culture medium includes chondroblasts. 
   
   
       4 . The method of  claim 1 , wherein the culture medium includes fibroblasts. 
   
   
       5 . The method of  claim 1 , wherein the culture medium includes stem cells. 
   
   
       6 . The method of  claim 1 , wherein the matrix develops into bone tissue. 
   
   
       7 . The method of  claim 1 , wherein the matrix develops into cartilage. 
   
   
       8 . The method of  claim 1 , wherein the matrix develops into ligament. 
   
   
       9 . The method of  claim 1 , wherein the matrix develops into tendon. 
   
   
       10 . The method of  claim 1 , wherein the matrix develops into a bone-tendon-bone composite. 
   
   
       11 . The method of  claim 1 , wherein the matrix develops into a cartilage-bone composite. 
   
   
       12 . The method of  claim 1 , wherein the tissue matrix includes stem cells. 
   
   
       13 . The method of  claim 1 , wherein the actuator that mimics forces produced in a natural bone joint. 
   
   
       14 . The method of  claim 1 , wherein the actuator that mimics forces produced in a knee joint. 
   
   
       15 . The method of  claim 1 , wherein the actuator that mimics forces produced in a hip joint. 
   
   
       16 . The method of  claim 1 , wherein the actuator that mimics forces produced in a shoulder joint. 
   
   
       17 . The method of  claim 1 , wherein the actuator that mimics forces produced in an elbow joint. 
   
   
       18 . The method of  claim 1 , wherein the actuator that mimics forces produced in a spine. 
   
   
       19 . The method of  claim 1 , wherein the actuator applies a compressive force. 
   
   
       20 . The method of  claim 1 , wherein the actuator applies tension. 
   
   
       21 . The method of  claim 1 , wherein the actuator applies an oscillating force. 
   
   
       22 . The method of  claim 1 , wherein the actuator applies a torsional or twisting force. 
   
   
       23 . The method of  claim 1 , wherein intermittent axial, torsional and bending loads are applied to produce a tubular bone. 
   
   
       24 . The method of  claim 1 , wherein compression alone is applied to produce cancellous bone. 
   
   
       25 . The method of  claim 1 , further including the steps of:
 supporting a scaffold material with the culture vessel; and   applying the force to the scaffold material through the culture medium so as to synthesize the tissue on the scaffold material.   
   
   
       26 . The method of  claim 1 , further including the step of measuring a physical property of the tissue during the synthesis thereof. 
   
   
       27 . The method of  claim 26 , wherein the magnitude of the force is correlated with the measured property. 
   
   
       28 . The method of  claim 26 , wherein the physical property is an elastic modulus or a Young's modulus.