In situ IGF-1 gene delivery to cells emerging from the injured anterior cruciate ligament

Andre F. Steinert, Meike Weber, Manuela Kunz, Glyn D. Palmer, Ulrich Nöth, Christopher H Evans, Martha M. Murray

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Ruptures of the anterior cruciate ligament (ACL) are common knee injuries that do not heal, even with surgical repair. Our research is directed towards developing novel, biological approaches that enable suture repair of this ligament. One promising strategy involves the insertion of a collagen hydrogel between the severed ends of the ACL. Cells migrate from the damaged ligament into the hydrogel and produce repair tissue. Here we have investigated the potential for augmenting this process by the transfer of insulin like growth factor (IGF) 1 cDNA to the repair cells using an adenovirus vector. The goal is to achieve direct, in situ gene delivery by loading the hydrogel with vector prior to its insertion into the defect. In a step-wise approach towards evaluating this process, we confirmed that monolayers of ACL fibroblasts were efficiently transduced by adenovirus vectors and continued to express transgenes when subsequently incorporated into the hydrogel; indeed, transgene expression persisted longer within collagen gels than in monolayer culture. Transfer of IGF-1 cDNA increased the cellularity of the gels and led to the synthesis and deposition of increased amounts of types I and III collagen, elastin, tenascin, and vimentin. The cells remained viable, even when subjected to high viral loads. Similar results were obtained when collagen hydrogels were preloaded with adenovirus prior to insertion into an experimental ACL lesion in vitro. These data confirm the promise of using vector-laden hydrogels for the in situ delivery of genes to cells within damaged ligaments and suggest novel possibilities for the biological repair of the ACL.

Original languageEnglish (US)
Pages (from-to)904-916
Number of pages13
JournalBiomaterials
Volume29
Issue number7
DOIs
StatePublished - Mar 2008
Externally publishedYes

Fingerprint

Anterior Cruciate Ligament
Insulin
Ligaments
Somatomedins
Hydrogel
Genes
Hydrogels
Adenoviridae
Repair
Collagen
Transgenes
Complementary DNA
Gels
Tenascin
Knee Injuries
Collagen Type III
Elastin
Vimentin
Monolayers
Collagen Type I

Keywords

  • Adenovirus
  • Anterior cruciate ligament
  • Collagen hydrogel
  • Gene transfer
  • IGF-1

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

In situ IGF-1 gene delivery to cells emerging from the injured anterior cruciate ligament. / Steinert, Andre F.; Weber, Meike; Kunz, Manuela; Palmer, Glyn D.; Nöth, Ulrich; Evans, Christopher H; Murray, Martha M.

In: Biomaterials, Vol. 29, No. 7, 03.2008, p. 904-916.

Research output: Contribution to journalArticle

Steinert, AF, Weber, M, Kunz, M, Palmer, GD, Nöth, U, Evans, CH & Murray, MM 2008, 'In situ IGF-1 gene delivery to cells emerging from the injured anterior cruciate ligament', Biomaterials, vol. 29, no. 7, pp. 904-916. https://doi.org/10.1016/j.biomaterials.2007.10.054
Steinert, Andre F. ; Weber, Meike ; Kunz, Manuela ; Palmer, Glyn D. ; Nöth, Ulrich ; Evans, Christopher H ; Murray, Martha M. / In situ IGF-1 gene delivery to cells emerging from the injured anterior cruciate ligament. In: Biomaterials. 2008 ; Vol. 29, No. 7. pp. 904-916.
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