Resurfacing with chemically modified hyaluronic acid and lubricin for flexor tendon reconstruction

We assessed surface coating with carbodiimide derivatized hyaluronic acid combined with lubricin (cd‐HA‐Lubricin) as a way to improve extrasynovial tendon surface quality and, consequently, the functional results in flexor tendon reconstruction, using a canine in vivo model. The second and fifth flexor digitorum profundus tendons from 14 dogs were reconstructed with autologs peroneus longus (PL) tendons 6 weeks after a failed primary repair. One digit was treated with cd‐HA‐Lubricin, and the other was treated with saline as the control. Six weeks following grafting, the digits and graft tendons were functionally and histologically evaluated. Adhesion score, normalized work of flexion, graft friction in zone II, and adhesion breaking strength at the proximal repair site in zone III were all lower in the cd‐HA‐Lubricin treated group compared to the control group. The strength at the distal tendon/bone interface was decreased in the cd‐HA‐Lubricin treated grafts compared to the control grafts. Histology showed inferior healing in the cd‐HA‐Lubricin group at both proximal and distal repair sites. However, cd‐HA‐Lubricin treatment did not result in any gap or rupture at either the proximal or distal repair sites. These results demonstrate that cd‐HA‐Lubricin can eliminate graft adhesions and improve digit function, but that treatment may have an adverse effect on tendon healing. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 969–975, 2013     

Surface modification counteracts adverse effects associated with immobilization after flexor tendon repair

Although post‐rehabilitation is routinely performed following flexor tendon repair, in some clinical scenarios post‐rehabilitation must be delayed. We investigated modification of the tendon surface using carbodiimide derivatized hyaluronic acid and lubricin (cd‐HA‐Lub) to maintain gliding function following flexor tendon repair with postoperative immobilization in a in vivo canine model. Flexor digitorum profundus tendons from the 2nd and 5th digits of one forepaw of six dogs were transected and repaired. One tendon in each paw was treated with cd‐HA‐Lub; the other repaired tendon was not treated. Following tendon repair, a forearm cast was applied to fully immobilize the operated forelimb for 10 days, after which the animals were euthanized. Digit normalized work of flexion (nWOF) and tendon gliding resistance were assessed. The nWOF of the FDP tendons treated with cd‐HA‐Lub was significantly lower than the nWOF of the untreated tendons (p < 0.01). The gliding resistance of cd‐HA‐Lub treated tendons was also significantly lower than that of the untreated tendons (p < 0.05). Surface treatment with cd‐HA‐Lub following flexor tendon repair provides an opportunity to improve outcomes for patients in whom the post‐operative therapy must be delayed after flexor tendon repair. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1940–1944, 2012     

Lubricin surface modification improves tendon gliding after tendon repair in a canine model in vitro

This study investigated the effects of lubricin on the gliding of repaired flexor digitorum profundus (FDP) tendons in vitro. Canine FDP tendons were completely lacerated, repaired with a modified Pennington technique, and treated with one of the following solutions: saline, carbodiimide derivatized gelatin/hyaluronic acid (cd‐HA‐gelatin), carbodiimide derivatized gelatin to which lubricin was added in a second step (cd‐gelatin + lubricin), or carbodiimide derivatized gelatin/HA + lubricin (cd‐HA‐gelatin + lubricin). After treatment, gliding resistance was measured up to 1,000 cycles of simulated flexion/extension motion. The increase in average and peak gliding resistance in cd‐HA‐gelatin, cd‐gelatin + lubricin, and cd‐HA‐gelatin + lubricin tendons was less than the control tendons after 1,000 cycles (p < 0.05). The increase in average gliding resistance of cd‐HA‐gelatin + lubricin treated tendons was also less than that of the cd‐HA‐gelatin treated tendons (p < 0.05). The surfaces of the repaired tendons and associated pulleys were assessed qualitatively with scanning electron microscopy and appeared smooth after 1,000 cycles of tendon motion for the cd‐HA‐gelatin, cd‐gelatin + lubricin, and cd‐HA‐gelatin + lubricin treated tendons, while that of the saline control appeared roughened. These results suggest that tendon surface modification can improve tendon gliding ability, with a trend suggesting that lubricin fixed on the repaired tendon may provide additional improvement over that provided by HA and gelatin alone. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:257–263, 2009     

Early healing of flexor tendon insertion site injuries: Tunnel repair is mechanically and histologically inferior to surface repair in a canine model.

Orthopedic injuries often require surgical reattachment of tendon to bone. Tendon ends can be sutured to bone by direct apposition to the bone surface or by placement within a bone tunnel. Our objective was to compare early healing of a traditional surface versus a novel tunnel method for repair of the flexor digitorum profundus (FDP) tendon insertion site in a canine model. A total of 70 tendon-bone specimens were analyzed 0, 5, 10 or 21 days after injury and repair, using tensile and range of motion mechanical testing, histology and densitometry. Ultimate force (a measure of repair strength) did not differ between surface and tunnel repairs at day 0. Both repair types had reduced strength at 10 and 21 days compared to 0 days, indicative of deterioration of suture grasping strength (tendon softening). At 21 days, tendons repaired in a bone tunnel had 38% lower ultimate force compared to surface repairs (p = 0.017). Histological findings were comparable between repair groups at 5 and 10 days but differed at 21 days, when we saw evidence of maturation of the tendon-bone interface in the surface repairs compared to an immature fibrous interface with no evidence of tendon-bone integration in the tunnel repairs. After accounting for bone removed by the tunnel, no difference in bone mineral density or trabecular bone volume existed between surface and tunnel repairs. If the results of our animal study extend to healing of the human FDP insertion, they indicate that FDP tendons should be reattached to the distal phalanx by suture to the cortical surface rather than suture in a bone tunnel.     

Effects of lubricant and autologous bone marrow stromal cell augmentation on immobilized flexor tendon repairs

The purpose of the study was to test a novel treatment that carbodiimide‐derivatized‐hyaluronic acid‐lubricin (cd‐HA‐lubricin) combined cell‐based therapy in an immobilized flexor tendon repair in a canine model. Seventy‐eight flexor tendons from 39 dogs were transected. One tendon was treated with cd‐HA‐lubricin plus an interpositional graft of 8 × 10⁵ BMSCs and GDF‐5. The other tendon was repaired without treatment. After 21 day of immobilization, 19 dogs were sacrificed; the remaining 20 dogs underwent a 21‐day rehabilitation protocol before euthanasia. The work of flexion, tendon gliding resistance, and adhesion score in treated tendons were significantly less than the untreated tendons (p < 0.05). The failure strength of the untreated tendons was higher than the treated tendons at 21 and 42 days (p < 0.05). However, there is no significant difference in stiffness between two groups at day 42. Histologic analysis of treated tendons showed a smooth surface and viable transplanted cells 42 days after the repair, whereas untreated tendons showed severe adhesion formation around the repair site. The combination of lubricant and cell treatment resulted in significantly improved digit function, reduced adhesion formation. This novel treatment can address the unmet needs of patients who are unable to commence an early mobilization protocol after flexor tendon repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:154–160, 2016.     

Chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cells

Reparative strategies for the treatment of injuries to tendons, including those of the rotator cuff of the shoulder, need to address the formation of the cartilage which serves as the attachment apparatus to bone and which forms at regions undergoing compressive loading. Moreover, recent work indicates that cells employed for rotator cuff repair may need to synthesize a lubricating glycoprotein, lubricin, which has recently been found to play a role in tendon tribology. The objective of the present study was to investigate the chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cells in monolayer and three‐dimensional culture, and to compare the behavior with bone marrow‐derived mesenchymal stem cells (MSCs). The results demonstrated that while tendon cells in various media, including chondrogenic medium, expressed lubricin, virtually none of the MSCs synthesized this important lubricating molecule. Also of interest was that the cartilage formation capacity of the tendon cells grown in pellet culture in chondrogenic medium was comparable with MSCs. These data inform the use of tendon cells for rotator cuff repair, including for fibrocartilaginous zones. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:716–725, 2010     

The tensile strength of various peripheral circumferential repair techniques in canine flexor tendons

The purpose of this study was to evaluate the tensile strength of six peripheral circumferential suture techniques, using a variable number of suture strands. Transverse lacerations were made in 184 fresh frozen canine flexor profundus tendons and repaired using only a 6-0 Prolene circumferential suture. The six running suture techniques were: Simple, Simple-locking, Lembert, Halsted, Cross-stitch and Lin-locking, and 6, 10, 14, and 20 suture strands were used. For each technique, the tensile strength gradually increased with the increased number of suture strands. The tensile strength of the Lin-locking technique (19–34 N) was greater than that of the other techniques, followed by Cross-stitch (16–33 N), Halsted (10–25 N), Lembert (8–23 N), Simple (6–12 N), and Simple-locking (5–8 N). The Lin-locking had the best holding power, but it was technically the most complicated to place. The Cross-stitch had good tensile strength values. The Simple and the Simple-locking had the lowest tensile strengths. From the viewpoints of tensile strength and technical skill, the Cross-stitch may be preferable to other suture techniques.     

The effect of hyaluronidase,phospholipase, lipid solvent and trypsin on the lubrication of canine flexor digitorum profundus tendon

Although the flexor digitorum profundus (FDP) tendon's gliding resistance is low, the lubrication mechanism that enables this is unclear. The principal lubricants in joints, such as hyaluronic acid, phospholipids, and lubricin, a lubricating glycoprotein, are known to be present in the canine tendon. In this study, we assessed the effect of these lubricants in the tendon by measuring gliding resistance before and after their removal. Canine FDP tendons were treated with hyaluronidase, phospholipase, lipid solvent, and/or trypsin. The gliding resistance of FDP tendons significantly increased after all treatments (p < 0.05). The largest effect on gliding resistance was observed after trypsin digestion. Scanning electron microscopy and immunostaining for hyaluronic acid and lubricin were used to qualitatively assess the tendon surface after treatments. The trypsin digestion produced the most irregular surface, with many exposed collagen fibers. The results of this study suggest that phospholipids, hyaluronic acid, and protein components are all involved in maintaining the low gliding resistance of the FDP tendon. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1225–1229, 2008     

Tendon fascicle gliding in wild type,heterozygous, and lubricin knockout mice

The objective of this study was to investigate the role of lubricin in the lubrication of tendon fascicles. Lubricin, a glycoprotein, lubricates cartilage and tendon surfaces, but the function of lubricin within the tendon fascicle is unclear. We developed a novel method to assess the gliding resistance of a single fascicle in a mouse tail model and used it to test the hypothesis that gliding resistance would be increased in lubricin knockout mice. Thirty‐six mouse tails were used from 12 wild type, 12 heterozygous, and 12 lubricin knockout mice. A 15 mm long fascicle segment was pulled proximally after being divided distally. The peak resistance during fascicle pullout and the fascicle perimeter were measured. Lubricin expression was evaluated by immunohistochemistry. The peak gliding resistance in the lubricin knockout mice was significantly higher than in the wild type (p < 0.05). Fascicles from heterozygous mice were intermediate in value, but not significantly different from either wild type or lubricin knockout fascicles in peak gliding resistance. No significant difference was found in fascicle perimeter among the three groups. No correlation was observed between fascicle perimeter and gliding resistance. While lubricin was detected by immunostaining on the fascicle surface in wild type and heterozygous mice, lubricin was not detectable in the tendons of knockout mice. We conclude that the absence of lubricin is associated with increased interfascicular friction and that lubricin may play an important role in interfascicular lubrication. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:384–389, 2011     

Spontaneous flexor tendon rupture of the flexor digitorum profundus secondary to an anatomic variant

We report a case of the flexor digitorum profundus tendon rupture of the little finger, which was predisposed by an anatomic variation of the tendon. Intraoperative findings and magnetic resonance imaging of the opposite hand suggested that the flexor digitorum profundus tendons of the ring and the little finger bifurcated. The patient had tendon reconstruction and regained function. We believe that reconstructing the tendon so that it resembles the normal anatomy prevents the recurrence of tendon rupture.     

Studies in flexor tendon reconstruction: biomolecular modulation of tendon repair and tissue engineering

The Andrew J. Weiland Medal is presented each year by the American Society for Surgery of the Hand and the American Foundation for Surgery of the Hand for a body of work related to hand surgery research. This essay, awarded the Weiland Medal in 2011, focuses on the clinical need for flexor tendon reconstruction and on investigations into flexor tendon biology. Reconstruction of the upper extremity is limited by 2 major problems after injury or degeneration of the flexor tendons. First, adhesions formed after flexor tendon repair can cause decreased postoperative range of motion and hand function. Second, tendon losses can result from trauma and degenerative diseases, necessitating additional tendon graft material. Tendon adhesions are even more prevalent after tendon grafting; therefore these 2 problems are interrelated and lead to considerable disability. The total costs in terms of disability and inability to return to work are enormous. In this essay, published work from the past 12 years in our basic science laboratory is summarized and presented with the common theme of using molecular techniques to understand the cellular process of flexor tendon wound healing and to create substances and materials to improve tendon repair and regeneration. These are efforts to address 2 interrelated and clinically relevant problems that all hand surgeons face in their practice.     

长屈肌腱转位手术治疗老年跟腱断裂的疗效分析

背景：慢性跟腱疾病发展到后期往往需要行肌腱转位治疗,长屈肌腱转位手术是常用的治疗方式。但老年患者的功能恢复、生活方式有别于其他人群。目的：探讨长屈肌腱转位手术治疗老年人跟腱断裂的临床效果。方法：回顾性分析2007年9月至2012年7月在我院行长屈肌腱转位手术的老年患者的病例资料（＞60岁）。共14例（16足）,男女各7例,年龄60~83岁,平均67.1岁。2例女性患者为双侧跟腱断裂同时行手术修补,均采用单切口长屈肌腱转位替代跟腱疗法。分别评估患者术前与术后美国足踝外科协会踝-后足评分（AOFAS-AH）,美国足踝外科协会趾-跖趾-趾间关节评分（AOFAS-MTPIP）,视觉模拟法（VAS）疼痛评分,跟腱断裂评分（ATRS）及手术相关并发症情况。最后进行统计学比较,评价患者足踝部功能恢复情况及患者满意情况。结果：14例患者术后获得21~67个月随访。AOFAS-AH评分从术前（68.2±6.2）分提高到术后的（93.2±5.3）分;AOFAS-MTPIP评分术前为（94.2±2.9）分,术后为（95.1±3.2）分;VAS评分术前（5.1±1.4）分,术后为（1.0±0.7）分;ARTS评分从术前（52.7±9.3）分提高到术后（86.3±10.3）分。16足术后均未出现伤口感染等手术并发症,也未在围手术期出现肺部感染、深静脉血栓等其他并发症。结论：长屈肌腱转位手术在老年人中的应用不但具有很好的手术疗效,并且安全性较高。     

克氏针远指间关节屈曲固定加牵引治疗小儿屈指肌腱止点断裂

正2008年8月~2015年6月,我们采用克氏针远指间关节屈曲固定加牵引治疗18例屈指深肌腱止点断裂患儿,疗效满意,报道如下。1材料与方法1.1病例资料本组18例,男12例,女6例,年龄1.5~5岁。其中拇指8例,示指6例,中指4例。伤口位于远指间关节附近,肌腱止点处断裂,形状为横行或斜行。致伤原因:水果刀割伤10     

Establishment of an in vivo turkey model for the study of flexor tendon repair

Flexor tendon injuries are common and pose a clinical challenge for functional restoration. The purpose of our study was to assess the adequacy of the turkey as a large animal model for flexor tendon injuries in vivo. Twenty‐four male turkeys underwent surgical flexor tendon cut and repair. Turkeys were allocated to five groups postoperatively: (1) foot casted in extension and sacrificed after 3 weeks; (2) foot casted in extension and sacrificed after 6 weeks; (3) foot casted in flexion and sacrificed after 3 weeks; (4) foot casted in flexion and sacrificed after 6 weeks; and (5) foot casted in flexion for 6 weeks and then free roaming allowed for an additional 3 weeks before sacrifice. After sacrifice, digits were collected and analyzed for adhesion formation, healing at the macrolevel and histologically, and biomechanical properties—including friction, work of flexion, stiffness, and strength of repair. All turkeys survived anesthesia and surgery. Tendon rupture occurred in all extension casts and in 11% of those casted in flexion. Friction and work of flexion were significantly higher in the repaired digit than the control digit. There was a correlation between duration of immobilization and repair strength. Histologically, the tendon healed with tenocytes migrating into the gap and producing collagen fibers. We have, for the first time, studied flexor tendon injury and repair using turkeys in terms of anesthesia, surgical procedures, postoperative care, and animal husbandry. The findings regarding functional and histological results from this novel avian model were comparable to the most commonly used mammal model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2497–2505, 2018.

     

Primary repair of a flexor tendon after a human bite

Successful uncomplicated primary closure of a human bite injury of the hand with simultaneous zone II flexor tendon injury has not been previously reported to our knowledge. We report the case of a man who was bitten on his left ring and right middle and index fingers. He was treated with antiseptic lavage, intravenous antibiotics, and operation. He had complete transsection of the flexor digitorum profundus at the middle phalanx. This was repaired primarily and he made a good recovery.     

Gliding resistance of flexor tendon associated with carpal tunnel pressure: A biomechanical cadaver study

The purpose of this study was to investigate the effect of carpal tunnel pressure on the gliding characteristics of flexor tendons within the carpal tunnel. Eight fresh human cadaver wrists and hands were used. A balloon was inserted into the carpal tunnel to elevate the pressure. The mean gliding resistance of the middle finger flexor digitorum superficialis tendon was measured with the following six conditions: (1) as a baseline, before balloon insertion; (2) balloon with 0 mmHg pressure; (3) 30 mmHg; (4) 60 mmHg; (5) 90 mmHg; (6) 120 mmHg. The gliding resistance of flexor tendon gradually increased as the carpal tunnel pressure was elevated. At pressures above 60 mmHg, the increase in gliding resistance became significant compared to the baseline condition. This study helps us to understand the relationship between carpal tunnel pressure, which is elevated in the patient with carpal tunnel syndrome (CTS) and tendon gliding resistance, which is a component of the work of flexion. These findings suggest that patients with CTS may have to expend more energy to accomplish specific motions, which may in turn affect symptoms of hand pain, weakness and fatigue, seen commonly in such patients. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:58–61, 2011