Potential of a Bioscaffold to Enhance the Healing of the MCL Following a Mop-End Tear: An Animal Model Study

Isolated medial collateral ligament (MCL) injuries occur frequently (95,000 per year in the US) and heal with conservative treatment. Long-term clinical outcome is generally excellent because the structural properties of the Femur-MCL-Tibia complex (FMTC) naturally return to normal especially the stiffness. However, the quality of the healing ligament, as described by its histomorphological appearance, as well as biochemical, mechanical, and viscoelastic properties, remain poor [37, 70, 108, 109, 116]. Functional tissue engineering techniques such as the use of extracellular matrix (ECM) bioscaffolds have shown promise in improving healing of soft tissues after injury. In particular, small intestine submucosa (SIS) is especially attractive due to its chemoattractant properties, organized fiber alignment, and natural concentration of growth factors [9, 13, 48]. The objective of this thesis is to use SIS to improve MCL healing in a clinically relevant injury model.

Sixteen New Zealand white rabbits were subjected to a mop-end tear (Weiss et al. 1991) in order to simulate a clinically relevant injury, which included damage to the ligament insertion sites, over-stretching of collagen fibers, and a frayed appearance of the torn ligament ends. After 12 weeks of healing, seven rabbits per group were euthanized and subjected to a well-established biomechanical testing protocol [111], including a load to failure test. The remaining rabbits (n=2 per group) were evaluated histologically.

It was found that SIS treatment resulted in a marked improvement for the tangent modulus of the healing MCL midsubstance over non-treatment (404 ± 120 MPa vs. 273 ± 91 MPa, respectively, p<0.05). However, this difference did not translate into a change in the measured structural properties of the FMTC. Nearly half of the specimens in each treatment group failed at the tibial insertion, this indicates asynchronous healing between the ligament insertion and midsubstance.

In conclusion, these results confirm SIS enhances the quality of the healing MCL. SIS positively effects the local healing response of an MCL regardless of injury model. This work provides a basis to explore the effect of applying SIS to ligaments which do not heal well naturally, such as the anterior cruciate ligament.

Year	Entry
2001	Provenzano P, Lakes R, Keenan T, Vanderby R Jr. Nonlinear ligament viscoelasticity. Ann Biomed Eng. October 2001;29(10):908-914.
1993	Kwan MK, Lin TH-C, Woo SL-Y. On the viscoelastic properties of the anteromedial bundle of the anterior cruciate ligament. J Biomech. April–May 1993;26(4-5):447-452.
2000	Funk JR, Hall GW, Crandall JR, Pilkey WD. Linear and quasi-linear viscoelastic characterization of ankle ligaments. J Biomech Eng. February 2000;122(1):15-22.
1972	Fung Y-CB. Stress-strain-history relations of soft tissues in simple elongation. In: Fung YC, Perrone N, Anliker M, eds. Biomechanics: Its Foundations and Objectives. Symposium on Biomechanics, its Foundations and Objectives; July 29-31, 1970. Englewood Cliff, NJ: Inc., Prentice-Hall International; 1972:181-208.
1981	Woo SL-Y, Gomez MA, Akeson WH. The time and history-dependent viscoelastic properties of the canine medical collateral ligament. J Biomech Eng. November 1981;103(4):293-298.
1982	Woo SL-Y. Mechanical properties of tendons and ligaments, I: quasi-static and nonlinear viscoelastic properties. Biorheology. 1982;19(3):385-396.
1983	Woo SL-Y, Gomez MA, Seguchi Y, Endo CM, Akeson WH. Measurement of mechanical properties of ligament substance from a bone-ligament-bone preparation. J Orthop Res. 1983;1(1):22-29.
2003	Elliott DM, Robinson PS, Gimbel JA, Sarver JJ, Abboud JA, Iozzo RV, Soslowsky LJ. Effect of altered matrix proteins on quasilinear viscoelastic properties in transgenic mouse tail tendons. Ann Biomed Eng. May 2003;31(5):599-605.
1981	Woo SL-Y, Gomez MA, Amiel D, Ritter MA, Gelberman RH, Akeson WH. The effects of exercise on the biomechanical and biochemical properties of swine digital flexor tendons. J Biomech Eng. February 1981;103(1):51-56.
1993	Fung YC. Biomechanics: Mechanical Properties of Living Tissues. 2nd ed. New York, NY: Springer-Verlag; 1993.
1995	Matyas JR, Anton MG, Shrive NG, Frank CB. Stress governs tissue phenotype at the femoral insertion of the rabbit MCL. J Biomech. February 1995;28(2):147-157.
1970	Cooper RR, Misol S. Tendon and ligament insertion: a light and electron microscopic study. J Bone Joint Surg. January 1970;52A(1):1-20, 170.
2003	Thomopoulos S, Williams GR, Soslowsky LJ. Tendon to bone healing: differences in biomechanical, structural, and compositional properties due to a range of activity levels. J Biomech Eng. February 2003;125(1):106-113.
1983	Frank C, Woo SL-Y, Amiel D, Harwood F, Gomez M, Akeson W. Medial collateral ligament healing: a multidisciplinary assessment in rabbits. Am J Sports Med. 1983;11(6):379-389.
1984	Simon BR, Coats RS, Woo SL-Y. Relaxation and creep quasilinear viscoelastic models for normal articular cartilage. J Biomech Eng. May 1984;106(2):159-164.
1987	Woo SL-Y, Inoue M, McGurk-Burleson E, Gomez MA. Treatment of the medial collateral ligament injury, II: structure and function of canine knees in response to differing treatment regimens. Am J Sports Med. January–February 1987;15(1):22-29.
1991	Weiss JA, Woo SL-Y, Ohland KJ, Horibe S, Newton PO. Evaluation of a new injury model to study medial collateral ligament healing: primary repair versus nonoperative treatment. J Orthop Res. July 1991;9(4):516-528.
1987	Nigul I, Nigul U. On algorithms of evaluation of Fung's relaxation function parameters. J Biomech. 1987;20(4):343-352.
2004	Abramowitch SD, Woo SL-Y. An improved method to analyze the stress relaxation of ligaments following a finite ramp time based on the quasi-linear viscoelastic theory. J Biomech Eng. February 2004;126(1):92-97.
1990	Woo SL-Y, Danto MI, Ohland KJ, Lee TQ, Newton PO. The use of a laser micrometer system to determine the cross-sectional shape and area of ligaments: a comparative study with two existing methods. J Biomech Eng. November 1990;112(4):426-431.
1988	Lee TQ, Woo SL-Y. A new method for determining cross-sectional shape and area of soft tissues. J Biomech Eng. May 1988;110(2):110-114.
1990	Schmidt MB, Mow VC, Chun LE, Eyre DR. Effects of proteoglycan extraction on the tensile behavior of articular cartilage. J Orthop Res. May 1990;8(3):353-363.
2002	Provenzano PP, Lakes RS, Corr DT, Vanderby R. Application of nonlinear viscoelastic models to describe ligament behavior. Biomech Model Mechanobiol. June 2002;1(1):45-57.
1992	Chimich D, Shrive N, Frank C, Marchuk L, Bray R. Water content alters viscoelastic behaviour of the normal adolescent rabbit medial collateral ligament. J Biomech. August 1992;25(8):831-837.
1984	Dortmans LJMG, Sauren AAHJ, Rousseau EPM. Parameter estimation using the quasi-linear viscoelastic model proposed by Fung. J Biomech Eng. August 1984;106(3):198-203.
1982	Woo SL-Y, Gomez MA, Woo Y-K, Akeson WH. Mechanical properties of tendons and ligaments, II: the relationships of immobilization and exercise on tissue remodeling. Biorheology. 1982;19(3):397-408.
1990	Woo SL-Y, Peterson RH, Ohland KJ, Sites TJ, Danto MI. The effects of strain rate on the properties of the medial collateral ligament in skeletally immature and mature rabbits: a biomechanical and histological study. J Orthop Res. September 1990;8(5):712-721.

Year

Entry

2001

Provenzano P, Lakes R, Keenan T, Vanderby R Jr. Nonlinear ligament viscoelasticity. Ann Biomed Eng. October 2001;29(10):908-914.

1993

Kwan MK, Lin TH-C, Woo SL-Y. On the viscoelastic properties of the anteromedial bundle of the anterior cruciate ligament. J Biomech. April–May 1993;26(4-5):447-452.

2000

Funk JR, Hall GW, Crandall JR, Pilkey WD. Linear and quasi-linear viscoelastic characterization of ankle ligaments. J Biomech Eng. February 2000;122(1):15-22.

1972

Fung Y-CB. Stress-strain-history relations of soft tissues in simple elongation. In: Fung YC, Perrone N, Anliker M, eds. Biomechanics: Its Foundations and Objectives. Symposium on Biomechanics, its Foundations and Objectives; July 29-31, 1970. Englewood Cliff, NJ: Inc., Prentice-Hall International; 1972:181-208.

1981

Woo SL-Y, Gomez MA, Akeson WH. The time and history-dependent viscoelastic properties of the canine medical collateral ligament. J Biomech Eng. November 1981;103(4):293-298.