2015 ISAKOS Biennial Congress ePoster #418

Long-Term In-Vivo Evaluation in Sheep of a Resorbable Scaffold for Regeneration of the Anterior Cruciate Ligament

Robert A. Stanton, MD, Fairfield, CT UNITED STATES
Nicky Bertollo, PhD, Randwick, NSW AUSTRALIA
Robert A. Arciero, MD, Farmington, CT UNITED STATES
Robert A. Poggie, PhD, Notre Dame De L'ile Perrot, Quebec CANADA
William R. Walsh, PhD, Randwick, NSW AUSTRALIA
Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Randwick, New South Wales, AUSTRALIA

The FDA has not cleared the following pharmaceuticals and/or medical device for the use described in this presentation. The following pharmaceuticals and/or medical device are being discussed for an off-label use: Soft Tissue Regeneration Inc, L-C Ligament

Summary: This paper describes the long term in-vivo performance and biomechanical properties of a Poly-L-Lactic Acid (PLLA) scaffold for regeneration of the ACL.

Abstract:

Background

ACL reconstruction is currently performed with auto- and allo- graft tissues and non-resorbable implants. Limitations including pain and morbidity of harvesting autograft, potential for disease transmission and variable properties of allograft, and poor performance of prosthetics continues to challenge this field. The hypothesis was that the PLLA device would provide similar results to autograft controls using measures of clinical function, histology, pathology, micro-CT, x-ray, and biomechanical strength. The PLLA device was made of 3-D braided PLLA fibers, with loose braid intra-articularly and tight braid for the bone tunnels.

Methods

An intra-articular ACL model in adult sheep was used. Autograft was doubled-over extensor tendon. Grafts were fixed with 7mm by 25mm titanium interference screws. ACL reconstructions were evaluated at 3, 6, 12, 18, 24, and 48 months with PLLA devices in 48 adult sheep, and (control) 4-stranded extensor tendons in 28 sheep. Measures of efficacy included clinical function, synovitis, serology, gross reaction, scoring of cartilage and menisci, bony fixation, ligamentization, radiography, micro-CT, MRI, pathology of major organs, and strength.

Results

Sheep with the PLLA devices were fully functional immediately following surgery while autograft sheep exhibited early morbidity. No adverse reactions were noted in the bone tunnels based on micro-CT, radiographs, MRI, and histology. Bone integration and biological fixation in the bone tunnels was noted at 3 months and improved with time establishing a new enthesis at the interface. Histology of the intra-articular portion of PLLA devices and autografts showed ligamentization at 3 months, increased collagen deposition with time, and a reconstituted ACL at 1 year. Intra-articularly, PLLA devices were intact at 3 and 6 months, and nearly resorbed at 1 year; remnant PLLA particles were observed at 12, 18, and 24 months. There was no evidence of synovitis; serology and gross findings were normal. Pathology of lymph nodes and organs indicated occasional PLLA particulate of approximately 10 to 25 microns in size; no local or systemic adverse effects were noted for the organs, and occasional inflammatory cells were observed in the lymph nodes. The strength of the BLB complex at 12 months was 601 N for PLLA and 422 N for autograft. There were no adverse findings.

Discussion

Histology of sheep with PLLA scaffolds at 12, 24, and 48 months showed a regenerated ACL that resembled auto graft reconstructions. Histology of PLLA grafts resembled autograft in terms of early load bearing, gradual resorption and load transfer to new tissue (no stress shielding), and maturation of tissue after 6 months. The lack of adverse reaction to PLLA is ascribed to the biocompatibility and high ratio of surface area to volume of the PLLA fibers. The difference in resorption of PLLA in bone versus intra-articularly is ascribed to the more biologically dynamic environment of the ACL. Immediate load bearing, and through 1-year indicated the PLLA device to possess the strength necessary for ACL reconstruction.

Conclusion

This study conclusively showed this PLLA device to regenerate a functional ACL and to provide similar results to autograft in an ovine model of ACL reconstruction.