AUTOGRAFT FIBROBLASTS AND NEOLIGAMENT FORMATION

Project Details

Description

Anterior cruciate ligament (ACL) injuries lead to progressive degeneration
of the knee joint and development of osteoarthritis in one-third of
untreated patients. In the U.S., over 42,000 patients per year require
surgical reconstruction of the ACL. Patellar tendon autografts are most
frequently used, but acute graft necrosis delays neoligament formation. In
theory, maintenance of graft viability should improve neoligament
formation. New approaches are needed to test this theory. Acellular collagen scaffold implants can induce tissue ingrowth and
perform mechanically similar to autografts after ACL reconstruction. The
proposed research involves development of 'autograft analogues'
(fibroblast-seeded collagen scaffolds) to test these hypotheses:
Neoligament formation can be improved by implanting viable autogenous
fibroblasts that proliferate and synthesize new matrix without undergoing
acute necrosis. Fibroblast-seeded autograft analogues can remodel to
approximate the structure and function of the ACL. The project has three
specific aims: 1. Measure and optimize fibroblast attachment, proliferation, and matrix
synthesis on fibroblast-seeded collagen scaffolds in vitro. Determine
fibroblast viability and collagen scaffold strength as a function of time
in vitro. 2. Evaluate neoligament formation, and neoligament remodeling, in ACLs
surgically reconstructed using: a) patellar tendon autografts; b) unseeded
collagen scaffolds; c) scaffolds seeded with intra-articular (ACL or
synovial) fibroblasts; and d) scaffolds seeded with extraarticular
(patellar tendon or skin) fibroblasts. 3. Evaluate the effects of mechanical loading on neoligament remodeling by
using the same groups of implants as unloaded grafts in the contralateral
knee. Neoligament tissue will be evaluated by biomechanical testing, histology,
and analyses of the collagen network, for acute and chronic ACL
reconstructions in rabbits. The ratio of viable seeded fibroblasts to
newly-ingrown fibroblasts in the neoligament will be determined using
fluorescent labelling and flow cytometry. Bone tunnel insertion sites
will be examined using tetracycline labelling. These studies will elucidate the role of autogenous fibroblasts and
mechanical loads in neoligament formation/remodeling. Autograft analogues
are potentially useful for clinical ACL reconstruction: fibroblasts could
be obtained from biopsy, cultured, seeded onto a collagen scaffold, and
implanted as an ACL substitute into the same patient.
StatusFinished
Effective start/end date5/1/944/30/05

Funding

  • National Institutes of Health: $286,264.00
  • National Institutes of Health
  • National Institutes of Health: $278,334.00
  • National Institutes of Health: $277,902.00
  • National Institutes of Health
  • National Institutes of Health: $270,635.00
  • National Institutes of Health
  • National Institutes of Health: $21,045.00
  • National Institutes of Health: $48,107.00
  • National Institutes of Health: $294,435.00
  • National Institutes of Health: $19,638.00
  • National Institutes of Health: $104,614.00
  • National Institutes of Health
  • National Institutes of Health: $20,328.00
  • National Institutes of Health: $46,706.00

ASJC

  • Medicine(all)

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