2015 ISAKOS Biennial Congress ePoster #408

A New Cell-Free Biodegradable Synthetic Artificial Ligament in the Rat Anterior Cruciate Ligament (ACL) Reconstruction

Yohei Kawakami, MD, PhD, Pittsburgh, PA UNITED STATES
Koji Takayama, MD, PhD, Kobe, Hyogo JAPAN
Yutaka Mifune, MD, PhD, Kobe JAPAN
Tomoyuki Matsumoto, MD, PhD, Kobe, Hyogo JAPAN
Ryosuke Kuroda, MD, PhD, Kobe, Hyogo JAPAN
Masahiro Kurosaka, MD, Kobe, Hyogo JAPAN
Freddie H. Fu, MD, Pittsburgh, PA UNITED STATES
Johnny Huard, PhD, Houston, TX UNITED STATES

Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA

FDA Status Cleared

Summary: Our wet electrospinning technique with artificial ligament could readily be exploited for ACL reconstruction without using allograft or autograft, leading to cellular infiltration and enhanced biomechanical strength.

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Abstract:

INTRODUCTION:Traditional ACL reconstruction is usually performed using an allograft or autograft, which has numerous limitations including donor site morbidity, decreased range of motion, and potential infection, which often leads to an extended period of rehabilitation. Although artificial grafts have become an attractive alternative to biological grafts over the last two decades; the use of non-degradable artificial ligaments have not been popular because they have many limitations including the development of synovitis and chronic inflammatory reactions that ultimately lead to poor ligamentization and a high failure rate. Therefore, the development of a new biodegradable synthetic graft could represent an important alternative for ACL reconstruction.
METHODS:We have recently engineered a biodegradable scaffold for ACL reconstruction using a wet electrospinning technique in which fibers of a biodegradable elastomer, poly (ester urethane) urea (PEUU), were concurrently deposited with electrosprayed serum-based culture medium. A reproducible model of ACL reconstruction was created in female Sprague-Dawley rats according to a previous report. We established four groups: 1) Wet PEUU artificial ligament (wet PEUU), 2) Dry PEUU artificial ligament (dry PEUU), 3) Dry polycaprolactone diol (PCL) artificial ligament (dry PCL), and 4) autologous flexor digitorum longus tendon (Tendon). The PCL prosthesis was chosen as a control in the study because PCL is widely use in commercially and PEUU is made from PCL. (n=20 in each group)
RESULTS:The wet PEUU graft qualitatively exhibited a greater degree of looping and more tortuosity and its biaxial mechanical property measurements were significantly more compliant in both circumferential and longitudinal axes than other artificial grafts in vitro. In vivo biomechanical strength was significantly higher in the artificial ligament groups than in the control tendon group at 4 weeks and was significantly greater in the wet PEUU group than in all the other groups at 8 weeks. Immunostaining for rat isolectin B4 and DAPI revealed cellular and blood vessel infiltration had occurred in the tendon and wet PEUU groups. On the other hand, no cellular infiltration was noted in the dry PEUU and PCL groups. The number of COL3A1 and aSMA positive cells was observed in the tendon and wet PEUU groups, but control implants of dry PEUU and PCL did not experience substantial contractile smooth muscle cell infiltration. The µCT analysis revealed that the bone tunnels was significantly smaller in the tendon and wet PEUU groups. Moreover, less inflammation induced by wet PEUU was confirmed.
DISCUSSION:We demonstrated that the wet PEUU grafts exhibited a striking therapeutic effect for rat ACL reconstruction by promoting cellular and blood vessel infiltration, alleviating inflammation and increasing biomechanical strength. Control implants of dry PEUU and PCL did not experience substantial cellular infiltration and did not exhibit native mechanical properties. Wet PEUU is designed to adequately function throughout a period of tissue ingrowth and scaffold remodeling and resulted in the creation of tissues that closely resembled native tissue and represents a regenerative approach likely to reduce complications seen with current replacement materials used for ACL reconstruction.