# JOINT CONTRACTURE--BIOMEDICAL/CHEMICAL CORRELATES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1989 · $205,919

## Abstract

We propose the continuation of studies on the stress dependence of
connective tissue.  The cumulative data from our past efforts and
those of others working in this field support the extension of
Wolff's Law to fibrous connective tissue, cartilage and other
support the extension of Wolff's Law to fibrous connective tissue,
cartilage and other specialized connective tissue.  Stress
perturbations are seen to have profound effects on connective
tissue hemostasis and on connective tissue repair.  Current
evidence on connective tissue homestasis and on connective tissue
repair.  Current evidence indicates that stress deprivation
produces profound and rapid deterioration of fibrous connective
tissue mechanical and structural properties due to increased matrix
turnover and haphazard deposition of the newly synthesized fibrils.
The recovery from this process roughly parallels its inception
except at the insertion site.  Insertion site weakness results from
osteoclastic resorption of the ligament attachment fibers along
with resorption of bone which is part of the osseous response to
stress deprivation.  Recovery from insertion site weakness appears
to be a very slow process, requiring more than a year to overcome
the changes induced in 2-3 mos.

We proposed to complete the descriptive phases of this work using
biochemical, histological and biomechanical tools and to develop
a comprehensive theory of stress effects on connective tissue.  It
has become apparent that the fibrous tissues are not uniform in
their anatomical, ultramorphological, biochemical or biomechanical
characteristics.  The ACL, for example, has been shown by our
laboratory to be populated largely by cells with transmission
electron microscopy (TEM) characteristics of fibrocartilaginous
tissue rather than fibroblasts, as previously assumed.  The
implications of this finding are far reaching with respect to
conceptual constructs dealing with repair and function of the
anterior cruciate ligament (ACL).  We have also observed profound
differences in structure and composition of tendons as compared
with ligaments, which lead us to the conclusion that more detailed
analysis of individual structures is required with respect to
stress enhancement or stress deprivation effects.  A comprehensive
theory cannot be developed by generalizing from single structures.
Finally, the utility of a series of hyaluronic acid (HA) products
for their efficacy in minimizing stress deprivation effects on the
joint composite is proposed.  HA has been observed to inhibit the
physical and biochemical changes of contracture formation in a
contracture model.  The availability of a range of HA products
makes the screening for efficacy a necessary and logical outgrowth
of the earlier work.

## Key facts

- **NIH application ID:** 3154827
- **Project number:** 5R01AR014918-18
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** Wayne H. Akeson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $205,919
- **Award type:** 5
- **Project period:** 1979-05-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154827

## Citation

> US National Institutes of Health, RePORTER application 3154827, JOINT CONTRACTURE--BIOMEDICAL/CHEMICAL CORRELATES (5R01AR014918-18). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154827. Licensed CC0.

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