Intrasynovial Flexor Tendon Repair Research Articles

The effect of variations in applied rehabilitation force on collagen concentration and maturation at the intrasynovial flexor tendon repair site

The biochemical means by which accelerated rehabilitation alters intrasynovial flexor tendon repair site collagen synthesis and extracellular matrix maturation are not fully understood. We hypothesized that an increased level of applied rehabilitative force in a clinically relevant animal model would hasten the maturation of the repair site extracellular matrix as demonstrated by total collagen and collagen cross-link assessment. Twenty-eight flexor digitorum profundus tendons from 14 adult dogs were transected and repaired. The animals received either low- or high-force rehabilitation and were killed 10, 21, and 42 days after surgery. A 10-mm segment of tendon surrounding the repair site was obtained. Biochemical analysis showed that total collagen concentration was significantly reduced at each time point, that the reducible cross-link ratio of dihydroxylysinonorleucine to hydroxylysinonorleucine was significantly increased at each time point, and that the nonreducible pyridinoline cross-link content was significantly decreased at 10 days in both rehabilitative groups. Total collagen content did not vary to a statistically significant degree with either time or as a function of rehabilitation type. Based on these findings several clinically relevant observations can be made. Increasing collagen concentration and repair site maturation do not explain the previously demonstrated increased tensile properties of tendon that occur between 3 and 6 weeks after repair. Higher force rehabilitation does not alter the biochemical composition of the healing tendon through 6 weeks. Coupled with other recent data these findings suggest that high-force rehabilitation does not stimulate accelerated healing after intrasynovial flexor tendon repair.

Quantitative variation in vascular endothelial growth factor mRNA expression during early flexor tendon healing: an investigation in a canine model

Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis, with direct mitogenic activity on cells of endothelial origin. We quantified the temporal accumulation of VEGF mRNA at the repair site of an in vivo canine intrasynovial flexor tendon repair and rehabilitation model by means of quantitative Northern blot analysis, in order to detail a molecular signal involved in the intrinsic angiogenic process that accompanies early flexor tendon healing. Significant accumulation of VEGF mRNA occurred at the flexor tendon repair site at 7 days post-operatively, with peak levels seen at post-operative days 7 and 10. Levels returned to baseline by day 14. Local VEGF mRNA accumulation at the repair site temporally precedes and is spatially distinct from the vascular ingrowth itself, which has been shown to occur maximally at day 17. These data suggest that cells within the flexor tendon repair site are involved in molecular processes other than the synthesis of extracellular matrix, such as modulation of angiogenesis.

Intrasynovial Flexor Tendon Repair

Rehabilitation methods that generate increased tendon force and motion have been advocated to improve results following intrasynovial flexor tendon repair. However, the effects of rehabilitation force and motion on tendon-healing may be masked by the high stiffness produced by newer suture methods. Our objective was to determine whether the biomechanical properties of tendons repaired by one of two multistrand suture methods were sensitive to an increased level of applied rehabilitation force. Two hundred and fourteen flexor digitorum profundus tendons from 107 adult dogs were transected and repaired. Dogs were assigned to one of four groups based on the rehabilitation method (low force [<5 N] or high force [17 N]) and the repair technique (four-strand or eight-strand core suture) and were killed between five and forty-two days after the procedure. Repair-site structural properties were determined by tensile testing, and digital range of motion was assessed with use of a motion-analysis system. Tensile properties did not differ between the low and high-force rehabilitation groups, regardless of the repair technique (p > 0.05). In contrast, tensile properties were strongly affected by the repair technique, with tendons in the eight-strand group having an approximately 35% increase in ultimate force and rigidity compared with those in the four-strand group (p < 0.05). Ultimate force did not change significantly with time during the first twenty-one days (p > 0.05); there was no evidence of softening in either of the repair or rehabilitation groups. Force increased significantly from twenty-one to forty-two days, while rigidity increased throughout the forty-two-day period (p < 0.05). Increasing the level of force applied during postoperative rehabilitation from 5 to 17 N did not accelerate the time-dependent accrual of stiffness or strength. Suture technique was of primary importance in providing a stiff and strong repair throughout the early healing interval. Our findings suggest that there be a reexamination of the concept that increases in force produced by more vigorous mobilization protocols are beneficial to tendon-healing. While more vigorous rehabilitation may help to improve hand function, we found no evidence that it enhances tissue-healing or strength in the context of a modern suture repair.

Nonviral in vivo gene therapy for tissue engineering of articular cartilage and tendon repair.

Heretofore, nonviral methods have been used primarily for in vitro transfection of cultured cell lines. These methods were substantially less efficient when compared with the use of viruses, particularly when used in vivo. Herein a three-step, highly efficient method of nonviral gene delivery is presented. Using this method, genes have been delivered successfully into tissues of orthopaedic importance with high-efficiency by nonviral means. Transforming growth factor-beta 1, parathyroid hormone related protein, and a marker gene were transfected into primary perichondrium and cartilage cells with efficiencies in excess of 70%. They overexpressed their cognate gene products showing efficacy of expression in a rabbit model of osteochondral defect repair. Using the same method, a marker gene was delivered into a canine model for intrasynovial flexor tendon injury and repair. This was achieved by direct gene delivery during surgery. An estimated 5 additional minutes were required during surgery to complete the transfection steps. High efficiency gene delivery was achieved in the flexor tendons, tendon sheaths, tendon pulleys, surrounding tissues, and skin. The efficiency of transfection approached 100% in the exposed superficial tissue layers and transfected cells were found several layers below the exposed tissue surfaces. The data show the potential of direct nonviral gene therapy in orthopaedics for ex vivo and in vivo applications.

Effects of increased in vivo excursion on digital range of motion and tendon strength following flexor tendon repair.

Postoperative rehabilitation is an important factor in determining functional outcome following intrasynovial flexor tendon repair. We hypothesized that a rehabilitation protocol that produced increased in vivo excursion would lead to increased digital range of motion and tendon strength and decreased adhesion formation in a canine model. Ninety-six flexor digitorum profundus tendons from 48 dogs were cut transversely and repaired by a multistrand suture technique. Postoperative rehabilitation was performed daily with a low excursion-low force (1.7-mm average excursion; < 10 N force) or a high excursion-low force (3.6 mm excursion; < 10 N force) protocol. After death of the dogs at 10, 21, or 42 days, specimens were evaluated for digital range of motion, tensile mechanical properties, elongation of the repair site, and adhesion formation. Our data indicate that the range of motion of digits whose tendons were at low or high excursion was similar to that of controls. Increased in vivo tendon excursion due to synergistic wrist motion did not significantly affect ex vivo flexion of the distal and proximal interphalangeal joints or tendon displacement (p > 0.05). Similarly, tensile properties (ultimate load, repair site rigidity, and repair site strain at 20 N and at failure) and length of the gap at the repair site were not significantly affected by increased excursion (p > 0.05). Severity of adhesion formation was reduced slightly by increased excursion (p = 0.04). Our findings indicate that 1.7 mm of tendon excursion is sufficient to prevent adhesion formation following sharp transection of the canine flexor tendon and that additional excursion provides little added benefit.

Integrin Expression is Upregulated During Early Healing in a Canine Intrasynovial Flexor Tendon Repair and Controlled Passive Motion Model

To explore crucial early molecular events involved in contact healing of the intrasynovial flexor tendon, integrin expression was evaluated at the transcriptional and post-transcriptional levels during the first two weeks following injury, repair and controlled passive motion in a canine model. Specifically, immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) techniques were employed to evaluate expression of the fibronectin, vitronectin and endothelial cell binding integrin receptor subunits α5, αv and α6, along with the common β1 subunit. The two techniques revealed increasing expression of the four subunits over the two week post-repair period. Immunohistochemistry revealed that β1 and α5 expression was concentrated in the epitenon layer near the repair site and interiorly within the wound area, while α6 was associated with capillary-forming endothelial cells near the wound. RT-PCR and quantitation by NIH image analysis demonstrated peak messenger RNA expression of β1 and α5 at ten days post-repair and peak expression of α6 and av at 15 days. The results in this study correlate well with previous results demonstrating increased fibronectin deposition and angiogenesis during the same time period in a similar injury/repair model.

Studies on the mechanism of diet-induced hepatic inactivation of vitamin D

The biochemical means by which accelerated rehabilitation alters intrasynovial flexor tendon repair site collagen synthesis and extracellular matrix maturation are not fully understood. We hypothesized that an increased level of applied rehabilitative force in a clinically relevant animal model would hasten the maturation of the repair site extracellular matrix as demonstrated by total collagen and collagen cross-link assessment. Twenty-eight flexor digitorum profundus tendons from 14 adult dogs were transected and repaired. The animals received either low- or high-force rehabilitation and were killed 10, 21, and 42 days after surgery. A 10-mm segment of tendon surrounding the repair site was obtained. Biochemical analysis showed that total collagen concentration was significantly reduced at each time point, that the reducible cross-link ratio of dihydroxylysinonorleucine to hydroxylysinonorleucine was significantly increased at each time point, and that the nonreducible pyridinoline cross-link content was significantly decreased at 10 days in both rehabilitative groups. Total collagen content did not vary to a statistically significant degree with either time or as a function of rehabilitation type. Based on these findings several clinically relevant observations can be made. Increasing collagen concentration and repair site maturation do not explain the previously demonstrated increased tensile properties of tendon that occur between 3 and 6 weeks after repair. Higher force rehabilitation does not alter the biochemical composition of the healing tendon through 6 weeks. Coupled with other recent data these findings suggest that high-force rehabilitation does not stimulate accelerated healing after intrasynovial flexor tendon repair. (J Hand Surg 2001;26A:841–846. Copyright © 2001 by the American Society for Surgery of the Hand.)