Literature DB >> 12038634

Induction of a neoarthrosis by precisely controlled motion in an experimental mid-femoral defect.

Dennis M Cullinane1, Amy Fredrick, Solomon R Eisenberg, Donna Pacicca, Michael V Elman, Cassandra Lee, Kristy Salisbury, Louis C Gerstenfeld, Thomas A Einhorn.   

Abstract

Bone regeneration during fracture healing has been demonstrated repeatedly, yet the regeneration of articular cartilage and joints has not yet been achieved. It has been recognized however that the mechanical environment during fracture healing can be correlated to the contributions of either the endochondral or intramembranous processes of bone formation, and to resultant tissue architecture. Using this information, the goal of this study was to test the hypothesis that induced motion can directly regulate osteogenic and chondrogenic tissue formation in a rat mid-femoral bone defect and thereby influence the anatomical result. Sixteen male Sprague Dawley rats (400 +/- 20 g) underwent production of a mid-diaphyseal, non-critical sized 3.0 mm segmental femoral defect with rigid external fixation using a custom designed four pin fixator. One group of eight animals represented the controls and underwent surgery and constant rigid fixation. In the treatment group the custom external fixator was used to introduce daily interfragmentary bending strain in the eight treatment animals (12 degree angular excursion), with a hypothetical symmetrical bending load centered within the gap. The eight animals in the treatment group received motion at 1.0 Hz, for 10 min a day, with a 3 days on, one day off loading protocol for the first two weeks, and 2 days on, one day off for the remaining three weeks. Data collection included histological and immunohistological identification of tissue types, and mean collagen fiber angles and angular conformity between individual fibers in superficial, intermediate, and deep zones within the cartilage. These parameters were compared between the treatment group, rat knee articular cartilage, and the control group as a structural outcome assessment. After 35 days the control animals demonstrated varying degrees of osseous union of the defect with some animals showing partial union. In every individual within the mechanical treatment group the defect completely failed to unite. Bony arcades developed in the experimental group, capping the termini of the bone segments on both sides of the defect in four out of six animals completing the study. These new structures were typically covered with cartilage, as identified by specific histological staining for Type II collagen and proteoglycans. The distribution of collagen within analogous superficial, intermediate, and deep zones of the newly formed cartilage tissue demonstrated preferred fiber angles consistent with those seen in articular cartilage. Although not resulting in complete joint development, these neoarthroses show that the induced motion selectively controlled the formation of cartilage and bone during fracture repair, and that it can be specifically directed. They further demonstrate that the spatial organization of molecular components within the newly formed tissue, at both microanatomical and gross levels, are influenced by their local mechanical environment, confirming previous theoretical models.

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Mesh:

Year:  2002        PMID: 12038634     DOI: 10.1016/S0736-0266(01)00131-0

Source DB:  PubMed          Journal:  J Orthop Res        ISSN: 0736-0266            Impact factor:   3.494


  16 in total

1.  Mechanical microenvironments and protein expression associated with formation of different skeletal tissues during bone healing.

Authors:  Gregory J Miller; Louis C Gerstenfeld; Elise F Morgan
Journal:  Biomech Model Mechanobiol       Date:  2015-03-31

2.  Correlations between local strains and tissue phenotypes in an experimental model of skeletal healing.

Authors:  Elise F Morgan; Kristy T Salisbury Palomares; Ryan E Gleason; Daniel L Bellin; Karen B Chien; Ginu U Unnikrishnan; Pui L Leong
Journal:  J Biomech       Date:  2010-05-23       Impact factor: 2.712

3.  Induction of fully stabilized cortical bone defects to study intramembranous bone regeneration.

Authors:  Meghan E McGee-Lawrence; David F Razidlo
Journal:  Methods Mol Biol       Date:  2015

4.  Mechanically induced structural changes during dynamic compression of engineered cartilaginous constructs can potentially explain increases in bulk mechanical properties.

Authors:  Thomas Nagel; Daniel J Kelly
Journal:  J R Soc Interface       Date:  2011-09-07       Impact factor: 4.118

5.  Adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models.

Authors:  Vaida Glatt; Romano Matthys
Journal:  J Vis Exp       Date:  2014-10-09       Impact factor: 1.355

6.  Stress fracture healing: fatigue loading of the rat ulna induces upregulation in expression of osteogenic and angiogenic genes that mimic the intramembranous portion of fracture repair.

Authors:  Gregory R Wohl; Dwight A Towler; Matthew J Silva
Journal:  Bone       Date:  2008-10-07       Impact factor: 4.398

Review 7.  Mechanotransduction and fracture repair.

Authors:  Elise F Morgan; Ryan E Gleason; Lauren N M Hayward; Pui L Leong; Kristy T Salisbury Palomares
Journal:  J Bone Joint Surg Am       Date:  2008-02       Impact factor: 5.284

8.  [Mechanobiology of fracture healing part 1 : Principles].

Authors:  L Claes
Journal:  Unfallchirurg       Date:  2017-01       Impact factor: 1.000

9.  Assessment of a mechano-regulation theory of skeletal tissue differentiation in an in vivo model of mechanically induced cartilage formation.

Authors:  Lauren Nicole Miller Hayward; Elise F Morgan
Journal:  Biomech Model Mechanobiol       Date:  2009-01-21

10.  Mechanical stimulation alters tissue differentiation and molecular expression during bone healing.

Authors:  Kristy T Salisbury Palomares; Ryan E Gleason; Zachary D Mason; Dennis M Cullinane; Thomas A Einhorn; Louis C Gerstenfeld; Elise F Morgan
Journal:  J Orthop Res       Date:  2009-09       Impact factor: 3.494

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