Effects of human amniotic fluid on peritendinous adhesion formation and tendon healing after flexor tendon surgery in rabbits

The effect of the topical application of human amniotic fluid (HAF) on peritendinous adhesion formation and tendon healing was investigated in 32 New Zealand adult rabbits. The long flexor tendons of the digits of each hind paw were completely divided and repaired with a modified Kessler technique. The rabbits were randomly divided into 4 experimental groups according to the type of repair used: sheath excision, sheath excision and local HAF application, sheath repair, and sheath repair and local HAF application. The extent of adhesions and the healing status of the tendons were macroscopically and histologically evaluated at 12 weeks. Tensile strength of the repaired tendons was measured biomechanically at 20 weeks. The least adhesion and the best healing were observed in tendons treated with sheath repair and HAF application. Tendons treated with HAF had significantly higher tensile load values. Topical application of HAF immediately after tenorrhaphy is significantly effective in preventing peritendinous adhesion formation without impairment of tendon healing in this rabbit model.     

Evaluating adhesion reduction efficacy of type I/III collagen membrane and collagen-GAG resorbable matrix in primary flexor tendon repair in a chicken model

Background

Reduction of peritendinous adhesions after injury and repair has been the subject of extensive prior investigation. The application of a circumferential barrier at the repair site may limit the quantity of peritendinous adhesions while preserving the tendon’s innate ability to heal. The authors compare the effectiveness of a type I/III collagen membrane and a collagen-glycosaminoglycan (GAG) resorbable matrix in reducing tendon adhesions in an experimental chicken model of a “zone II” tendon laceration and repair.

Methods

In Leghorn chickens, flexor tendons were sharply divided using a scalpel and underwent repair in a standard fashion (54 total repairs). The sites were treated with a type I/III collagen membrane, collagen-GAG resorbable matrix, or saline in a randomized fashion. After 3 weeks, qualitative and semiquantitative histological analysis was performed to evaluate the “extent of peritendinous adhesions” and “nature of tendon healing.” The data was evaluated with chi-square analysis and unpaired Student’s t test.

Results

For both collagen materials, there was a statistically significant improvement in the degree of both extent of peritendinous adhesions and nature of tendon healing relative to the control group. There was no significant difference seen between the two materials. There was one tendon rupture observed in each treatment group. Surgical handling characteristics were subjectively favored for type I/III collagen membrane over the collagen-GAG resorbable matrix.

Conclusion

The ideal method of reducing clinically significant tendon adhesions after injury remains elusive. Both materials in this study demonstrate promise in reducing tendon adhesions after flexor tendon repair without impeding tendon healing in this model.     

A lactoferrin-derived peptide (PXL01) for the reduction of adhesion formation in flexor tendon surgery: an experimental study in rabbits

Injuries to flexor tendons can lead to loss of finger function after healing due to adhesion formation. The aim of this study was to assess the efficacy and safety of the new peptide, PXL01, in the prevention of peritendinous adhesions. The effect of a single intraoperative administration of PXL01 in sodium hyaluronate on mobility of the affected digit after surgery was assessed in a rabbit model by measuring total active motion, metatarsophalangeal-claw distance and resistance to bending the digits. Load-to-failure testing was done in the same specimens to assess tendon healing. The results demonstrated that a single application of PXL01 in sodium hyaluronate significantly improved mobility of the treated digits compared with the digits in which the same surgery was carried out but no treatment was provided. No negative effects on tendon healing were observed in connection with the treatment.     

Cross-linked cartilage acellular matrix film decreases postsurgical peritendinous adhesions

Cartilage extracellular matrix contains antiadhesive and antiangiogenic molecules such as chondromodulin-1, thrombospondin-1, and endostatin. We have aimed to develop a cross-linked cartilage acellular matrix (CAM) barrier for peritendinous adhesion prevention. CAM film was fabricated using decellularized porcine cartilage tissue powder and chemical cross-linking. Biochemical analysis of the film showed retention of collagen and glycosaminoglycans after the fabrication process. Physical characterization of the film showed denser collagen microstructure, increased water contact angle, and higher tensile strength after cross-linking. The degradation time in vivo was 14 d after cross-linking. The film extract and film surface showed similar cell proliferation, while inhibiting cell migration and cell adhesion compared to standard media and culture plate, respectively. Application of the film after repair resulted in similar tendon healing and significantly less peritendinous adhesions in a rabbit Achilles tendon injury model compared to repair only group, demonstrated by histology, ultrasonography, and biomechanical testing. In conclusion, the current study developed a CAM film having biological properties of antiadhesion, together with biomechanical properties and degradation profile suitable for prevention of peritendinous adhesions.     

The effects of a combination of hyaluronic and amniotic membrane on the formation of peritendinous adhesions after flexor tendon surgery in chickens

We have investigated the effects of the intra-operative application of a combination of hyaluronic acid and amniotic membrane on adhesions in the flexor tendons of a chicken model. We used 144 tendons which were partially divided and then repaired by a modified Kessler technique. There were four test groups: group 1, simple tendon repair, group 2, repair site wrapped with amniotic membrane, group 3, hyaluronic acid injected around the repair site, and group 4, repair site wrapped with amniotic membrane and hyaluronic acid injected within it. At three and six weeks, the extent of the adhesions and the healing of the tendon were evaluated macroscopically and histologically. The range of movement of the toe and tensile strength of the repaired tendons were measured at 20 weeks. The least adhesions were observed in group 4 but no significant difference was found in the healing of the tendons. Overall, the intra-operative application of a combination of hyaluronic acid and amniotic membrane appears to be effective in preventing adhesions of the flexor tendon.     

A new material for prevention of peritendinous fibrotic adhesions after tendon repair: oxidised regenerated cellulose (Interceed), an absorbable adhesion barrier

In this experimental study, we aimed to examine the ability of absorbable oxidised regenerated cellulose (Interceed, TC-7, Johnson & Johnson, USA) to inhibit the formation of peritendinous fibrotic adhesions after tendon repair in rats. Both Achilles tendons of 23 female Wistar-Albino rats weighing between 350 and 450 grams were cut and repaired. On the right side, Interceed absorbable adhesion barriers were wrapped around the repaired tendon (group I). On the left, the same procedures were applied except for the Interceed wrapping and these were grouped as control (group II). Animals were sacrificed at postoperative day 28 and macroscopic and histological examination was performed. All the animals survived and no tendon rupture was observed. No wound dehiscence, wound infection or exposure of repaired tendons occurred. Macroscopically, there were three (13.1%) tendons without adhesion formation and 20 (86.9%) tendons with inferior adhesion formation in group I; on the other hand, there were 16 tendons (69.5%) with medium grade adhesion formation and seven tendons (30.5%) with severe peritendinous adhesion formation in group II (control group) (p<0.05). Histologically, adhesion formation was absent in 11 tendons (47.8%) and slight in 12 tendons (52.2%) in group I; while in group II, it was slight in two (8.6%), moderate in 15 (65.2%) and severe in six tendons (26.2%) (p<0.05). Sixteen (69.5%) of 23 tendons in group I and 11 (47.8%) of 23 tendons in group II showed no inflammatory reaction (p<0.05). Nineteen (82.6%) tendons in group I and only one tendon in group II showed excellent to good tendon healing (p=0.00). According to our results, we feel that Interceed may have an intraoperative role to play in the reduction of adhesions after surgical tendon repair. This study suggests that absorbable oxidised regenerated cellulose merits further evaluation as a potential treatment to inhibit the formation of peritendinous adhesions. Rigorous and extensive controlled trials should be undertaken on patients undergoing tendon repair with or without this barrier.     

Prevention of peritendinous adhesions following flexor tendon injury with seprafilm

Peritendinous adhesions are the most important complication of flexor tendon injury. In this study, Seprafilm was used for the prevention of peritendinous adhesions following flexor tendon repair. Seprafilm Bioresorbable Membrane (Genzyme Corporation, Cambridge, MA) contains sodium hyaluronate and carboxymethyl cellulose. Thirty New Zealand white male rabbits were divided equally into 3 groups. In all groups, the deep flexor tendon of the third finger of the left back foot was cut and repaired by Kessler-Tajima suture technique. In the first study group following tendon repair, Seprafilm was wrapped around the repaired tendon. In the second study group, sodium hyaluronate gel was injected to the operation field after tendon repair. In the control group, no external material was applied to the field. The study groups had better range of motion. Histopathologically, study groups had less adhesions compared with the control groups. As a result, it was concluded that in rabbit the peritendinous adhesions following flexor tendon repairs could be lowered with Seprafilm and hyaluronic acid.     

Injectable ibuprofen: preliminary evaluation of its ability to decrease peritendinous adhesions

Peritendinous adhesions continue to limit the full return of hand function following flexor tendon injury and repair. Pilot studies in rabbits demonstrated the ability of ibuprofen (Motrin) to reduce intra-abdominal adhesions. In this study, ibuprofen injected at the site of flexor tendon repair significantly reduced the restrictive effects of peritendinous adhesions in primates.     

The use of amniotic membrane in flexor tendon repair: an experimental model

BACKGROUND: The objective of this study was to investigate the use of amniotic membrane as a long-term bioprosthesis in hand surgery.The role of the amniotic membrane was investigated in chickens with regard to the prevention of adhesion formation following tendon repair in zone II. METHODS: In the control group, the flexor tendon sheath was excised and the tendon repaired. In group II, both the flexor digitorum profundus tendon and its sheath were repaired. In group III, the repaired tendon was covered with amniotic membrane. Histological evaluation of the repaired tendons were done at 3, 6 and 12 weeks. RESULTS: Results of histologic examination demonstrated that use of the amniotic membrane significantly reduced the amount of adhesion compared with the other groups. Three months after implantation no remnants of amniotic membrane could be identified at the tendon repair site. CONCLUSIONS: Amniotic membrane is easily prepared, and because of its cost effectiveness, its use in the prevention and treatment of adhesions should always be kept in mind.     

The use of a hydrogel sealant on flexor tendon repairs to prevent adhesion formation

The prevention of peritendinous adhesions after zone II flexor tendon repair poses a significant challenge to hand surgeons. This study evaluates a hydrogel sealant (FocalSeal-L) as a barrier to peritendinous adhesion formation. The deep flexors of toes 2 through 4 were divided and repaired in 30 chickens. Chickens were randomized to tendon repair with (n = 15) or without (n = 15) FocalSeal-L. Each group was further randomized to have their tendons studied postoperatively at 3 (n = 10), 6 (n = 10), or 12 (n = 10) weeks. Histologic evaluation revealed decreased peritendinous adhesion formation in the FocalSeal-L group. Biomechanical analysis demonstrated a decrease in work of flexion in the FocalSeal-L group that was most pronounced at 6 weeks (P = 0.0020). There was no significant difference in breaking strength. Apparently, an effective barrier to peritendinous adhesion formation, this sealant system is easy to use, biocompatible, and bioresorbable. In addition, it is not bulky or restrictive to tendon glide.     

Thermal preconditioning prevents peritendinous adhesions and inflammation

Adhesion formation is one of the foremost obstacles to a reliably good outcome in tendon and joint surgery. Thermal preconditioning has been found to reduce the inflammatory response through the induction of molecular chaperone expression, a recently described family of cytoprotective intracellular proteins. The authors analyzed the effect of thermal preconditioning on the inflammatory response to surgery, on tendon healing, and on the formation of peritendinous adhesions in 16 New Zealand White rabbits. Very significant decreases in adhesion formation and in the gliding and dimensions of tendons in animals that had thermal preconditioning were found. Tendons from these animals also showed a decreased level of adhesion formation and a significantly diminished inflammatory response on histologic examination with no biomechanically significant deleterious effect on the strength of tendon healing on testing load to failure. These findings are consistent with induction of heat shock proteins by hyperthermic pretreatment. Such prevention of peritendinous adhesions and the inflammatory response to injury and surgery without compromising healing are findings that have significant implications for tendon surgery and all surgery involving joints and soft tissues.     

Revitalized and synovialized allograft for intrasynovial flexor tendon reconstruction in an in vivo canine model

This study was to test our hypothesis that flexor tendon reconstruction with an allograft revitalized with bone marrow stromal cells (BMSCs) and synovialized with carbodiimide derivatized autologous synovial fluid (cd‐SYN) would result in better digit functional restoration than the conventional allograft tendon. A total of 32 flexor digital profundus tendons from the second and fifth digit of 16 dogs were created a repair failure model first. Then, failed‐repaired tendons were reconstructed with either a revitalized‐synovialized allograft tendon or a clinical standard autograft tendon (control group). The allograft tendon was seeded with autologous BMSCs in multiple slits and the graft surface was coated with cd‐SYN. A 6 weeks after tendon reconstruction, the digits were harvested and evaluated for digit function, adhesion status, tendon gliding resistance, attachment strength, cell viability, and histologic factors. The allograft group had significantly improved digit function compared with the control group through decreased work of flexion, increased digit range of motion under 2‐Newton force, and less adhesion score (p < .05). However, the distal attachment‐site strength and stiffness in the allograft tendon were significantly weaker than the autografts (p < .05). No significant difference was found for gliding resistance. Histologically, allograft tendons coated with allograft had smoother surfaces and showed tendon‐to‐bone and tendon‐to‐tendon incorporation. Viable BMSCs were found in the tendon slits 6 weeks after the graft. In conclusion, cellular lubricant‐based modification of allograft tendons improved digit function and reduced the adhesions compared with autograft for flexor tendon reconstruction. However, improvement of graft‐to‐host tendon healing is still challenging. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2218–2227, 2018.

     

Chondroitin sulfate-coated polyhydroxyethyl methacrylate membrane prevents adhesion in full-thickness tendon tears of rabbits

Polyhydroxyethyl methacrylate (pHEMA) membranes coated on one side with chondroitin sulfate (CS) were used to block adhesion physically and to reduce friction between healing flexor tendons and the surrounding tissue in rabbit forepaws after surgical repair. Digits with pHEMA-only, standard tendon sheath repair, and with no sheath repair were the controls. Over 12 weeks the CS-coated membranes were evaluated for joint flexion, adhesion limitation, and tendon healing progress. The membranes initially allowed for better flexion (ie, for 6 weeks), but their relative superior effectiveness faded afterward. Histology showed that adhesions were less severe and healing was better in the CS-pHEMA membranes at 3 and 6 weeks. If further studies determine precise amounts or thicknesses of CS coats that will maximize its healing properties, CS-pHEMA should prove useful in clinical settings in which restoration of tendon sheath integrity with a minimum of adhesions is not possible.     

Flexor tendon healing and adhesion formation after Sterispon wrapping: a study in the rabbit

The influence of Sterispon (Allen & Hanbury) wrapping on the healing of the rabbit flexor digitorum profundus tendon sutured within the digital sheath was studied. Control tendons healed in 2 weeks in association with thick adhesions. The wrapped tendons were surrounded with fewer adhesions, but 50 per cent separated. Healing was delayed until adhesions reached the suture site. A sheath of a single layer of mesothelial cells formed on the surface of the Sterispon opposite the tendon and this markedly reduced adhesions at the suture site. The cellular reaction was bland.Sterispon wrapping had a similar effect on tendon healing and adhesion formation as wrapping with other non-absorbable substances and the results support the theory that healing in the digital sheath is necessarily mediated through the formation of adhesions. Sterispon wrapping has been helpful after tenolysis operations.     

Biomechanical and histologic comparison of Achilles tendon ruptures reinforced with intratendinous and peritendinous plantaris tendon grafts in rabbits: an experimental study

Introduction We hypothesized that the closer the reinforcing graft was to the repair zone, the more strength the healed tendon would achieved. Therefore, we compared the ruptured rabbit Achilles tendons reinforced with intratendinous and peritendinous plantaris grafts.Materials and methods The experimental study was performed on Achilles tendons of 20 rabbits. First, they were divided into two groups: group I (n=10) underwent intratendinous graft and end-to-end tenorraphy, and group P (n=10) were repaired end-to-end and then reinforced with a peritendinous plantaris graft. An above-knee cast was applied during 6 weeks postoperatively. The two groups were compared to each other biomechanically and histologically. Seven randomly selected rabbits from each group were used for biomechanical evaluation. The remaining six rabbits (three from each group) were used for histologic comparison. Non-operated sides (n=20) served as the control group.Results The mean maximum load at rupture of the repaired and control groups was 159.9±31 N, 83±7.5 N, and 207.5±35 N for group I, group P, and the control group, respectively. Values between groups were significantly different considering maximum load and absorbed energy to rupture. There was no significant difference between groups I and P in respect to strain. Control group tendons (groups I-C and P-C) had significantly more lengthening capability than operated tendons. Macroscopically, group I tendons were thicker and stiffer than group P tendons. Histologically, differences between the group I and group P specimens revealed that the healing process was faster in tendons augmented intratendinously.Conclusions In reinforcing Achilles tendon repair, the site of the tendon graft affected the result. When the graft was used intratendinously, the healed tendon was more similar biomechanically to normal tendon and had more graft-tendon orientation histologically than the tendon augmented peritendinously.This study was performed at the Biomechanic Laboratory of Middle East Technical University (METU) and Animal Experimental Research Laboratory of Osmangazi University in Turkey. The experiments comply with the current law of our country     

Effect of hyaluronic acid/chondroitin sulfate on healing of full-thickness tendon lacerations in rabbits

Viscoat, a high-molecular-weight, highly purified hyaluronic acid (HA) and chondroitin sulfate (CS) compound, was instilled around rabbit plantaris tendon following full-thickness laceration and surgical repair. After 3 weeks of immobilization, no significant difference in adhesion strength or tensile strength of the healing tendons existed between Viscoat-treated tendons and controls. This contradicts previous studies which suggest that hyaluronic acid reduces postoperative tendon adhesions. Further studies examining tendon adhesions after less severe degrees of tendon injury and using direct, quantitative measurement techniques are warranted to demonstrate whether HA has a beneficial effect on tendon healing.     

The effect of fibrin glue on tendon healing and adhesion formation in a rabbit model of flexor tendon injury and repair

Abstract

Fibrin glue has been widely used in a variety of surgical procedures to promote haemostasis and tissue bonding. It can also be used as a cell carrier for stem cells on tendons. However, the data about the effect of fibrin glue on flexor tendon healing is very limited. The present study examined the role of fibrin glue TISSEEL® in a rabbit model of flexor tendon injury. The rabbits were killed 3 or 8 weeks after the operation. The range-of-motion of the fingers and biomechanical properties of tendons were measured and compared between the control group and TISSEEL-treated group. The findings have shown that the range-of-motion in the TISSEEL-treated group was significantly different from that of the control group at 3 weeks after the operation. However, there is no significant difference in range-of-motion at 8 weeks after the operation. Moreover, there is no significant difference in biomechanical properties between the control group and TISSEEL-treated group. The results indicate that TISSEEL may attenuate adhesion formation at the early stage of flexor tendon repair. However, there is no significant effect on biomechanical features during tendon repair. In conclusion, this study has shown that it may be safe to use TISSEEL in tissue engineering applications for tendon regeneration and healing.     

Postoperative stiffness and adhesion formation around repaired and immobilized Achilles tenotomies are prevented using a model of heat shock protein induction

BACKGROUND: Tendon repair and subsequent immobilization is frequently complicated by postoperative stiffness secondary to inflammation and peritendinous adhesions. Thermal preconditioning is known to reduce inflammation by inducing formation of cytoprotective heat shock proteins. This study evaluates the role of thermal preconditioning following complete division and repair of the Achilles tendon, with subsequent immobilization, mimicking the typical clinical scenario. MATERIALS AND METHODS: Twenty-four New Zealand White rabbits were used in the study. The treatment group underwent thermal preconditioning, by elevating their core temperature to 41.5 degrees C for 20 minutes. The Achilles tendon of the hindlimb was divided and repaired 18 hours following thermal preconditioning. The animals were sacrificed following 3 weeks of immobilization. Range of movement of the ankle, tendon gliding, quantity of adhesions, and weight of repaired tendons were assessed. RESULTS: Loss of range of movement at the ankle was significantly less in the treatment group versus controls (P = 0.02). The quantity of adhesions and weight of the repaired tendons were significantly reduced in the treatment group (P = <0.001 and P = 0.005, respectively). Tendon gliding relative to the surrounding soft tissue was also significantly improved in the treatment group (P = 0.002). CONCLUSION: Preconditioned animals demonstrated a significantly better range of ankle movement, decreases in adhesion formation and in the gliding, and dimensions of tendons. Thermal preconditioning therefore has the potential to improve clinical results in tendon surgery following repair and immobilization.     

Prevention of peritendinous adhesions using a hyaluronan‐derived hydrogel film following partial‐thickness flexor tendon injury

Peritendinous adhesions are an important complication of flexor tendon injury. Three hyaluronan (HA)‐derived biomaterials were evaluated for the reduction of peritendinous adhesions following partial‐thickness tendon injury in rabbits. Rabbits (n = 24) were divided into three groups (n = 8 per group), which were used for gross evaluation, histologic assessment, or biomechanical testing. The fourth and third toes from both hindpaws of each rabbit were randomly assigned to one of four treatments: (i) untreated control, (ii) Seprafilm®, (iii) Carbylan?‐SX in situ crosslinked hydrogel, and (iv) preformed Carbylan?‐SX film. Rabbits were sacrificed at 3 weeks postsurgery and evaluated anatomically, histologically, and mechanically. All materials used reduced adhesions relative to untreated controls for all three evaluations. Both the gross anatomic and histologic results revealed that Carbylan?‐SX film was statistically superior to Seprafilm® and Carbylan?‐SX gel in preventing tendon adhesion formation. In biomechanical tests, the Carbylan?‐SX film‐treated hindpaws required the least force to pull the tendon from the sheath. This force was statistically indistinguishable from that required to extrude an unoperated tendon (n = 8). Carbylan?‐SX gel was less effective than Carbylan?‐SX film but superior to Seprafilm® for all evaluations. A crosslinked HA‐derived film promoted healing of a flexor tendon injury without the formation of fibrosis at 3 weeks postoperatively. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:562–569, 2008     

TGF-β1抗体复合生物蛋白胶预防鞘管区屈肌腱粘连的组织学观察

[目的]研究TGF-β1抗体(transforming growth factor-β1antibody,TGF-β1Ab)复合生物蛋白胶(fibrin glue,FG)预防鞘管区屈肌腱粘连的作用和对肌腱愈合的影响.[方法]成年雄性来亨鸡72只随机平均分为4组,每组18只.左足第3趾趾深屈肌腱横断,四股交叉缝合肌腱,鞘管未缝合.按鞘管区给药分为4组:A组TGF-β1Ab、B组FG、C组TGF-β1Ab+FG、D组生理盐水.仅术中注入一次药物.术后1、3、8周,每组各取6只鸡第3趾行大体及组织学观测.[结果]大体观察:术后1、3、8周肌腱粘连程度分级A组与B组无统计学差异(P＞0.05),C组与其余3组比较有统计学差异(P＜0.05).组织学观测:术后3、8周A、B、D组胶原纤维排列紊乱,C组胶原纤维排列整齐.[结论]TGFβ1抗体复合生物蛋白胶可以有效预防术后肌腱粘连,不影响肌腱的正常愈合进程.