Auto‐crosslinked hyaluronic acid gel accelerates healing of rabbit flexor tendons in vivo

This study's purpose was to assess the in vivo effect of auto‐crosslinked hyaluronic acid (HA) gel, a natural HA derivative with increased viscosity and tissue residence time, on adhesions and healing of injured and surgically repaired rabbit digital flexor tendons. The second and third right deep digital flexor tendons from 48 rabbits (n = 96 tendons) were cut and repaired with a modified Kessler and running peripheral suture. Animals were randomized to two groups, receiving either HA gel or saline injected around both freshly repaired tendons. After 2, 3, 6, and 12 weeks, six rabbits in each group were euthanized. Tendon pull‐out force and breaking strength were measured as a value for adhesion formation and tendon healing, respectively. A histological assessment of adhesions and healing was related to the mechanical results. A significantly faster increase in breaking strength was found in HA gel‐treated compared to saline‐treated tendons; this coincided with a significantly accelerated tissue repair response after injury. No significant difference in adhesion formation was found between the two groups at any time. Our results indicate a significant acceleration of in vivo healing of tendons treated with HA gel. Adhesion formation was unaffected. These results could have important clinical value in promoting rehabilitation after tendon injury. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:408–415, 2009     

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.     

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     

Effect of hyaluronic acid on the excursion resistance of tendon grafts. A biomechanical study in a canine model in vitro

The excursion resistance between the tendon and pulley is an important factor contributing to the limitation of function after surgery to the hand. The administration of hyaluronic acid (HA) in the early rehabilitation after tendon grafting may help to prevent adhesions. We evaluated changes in the excursion resistance between potential sources of flexor tendon grafts and the annular pulley in a canine model after administration of HA. The intrasynovial and extrasynovial tendons were soaked in 10 mg/ml of HA for five minutes. The excursion resistance between these tendons and the annular pulley of an intact proximal phalanx and that of the same tendons of the opposite foot without administration of HA were evaluated. The tendon of flexor digitorum profundus of the second toe without administration of HA was used as a control. The gliding resistance of canine tendons was significantly decreased after the administration of HA especially in the extrasynovial tendons. Our findings suggest that the administration of HA may improve the gliding function of a flexor tendon graft.     

Hyaluronan in flexor tendon repair

This study assesses the effect of a preparation of hyaluronan (hyaluronic acid) applied topically at the time of flexor tendon repair in a well-established model. The hypothesis is that hyaluronic acid applied topically at the time of flexor tendon repair will decrease adhesions, and will improve clinically the gliding function of the repaired flexor tendon. After transection and repair of the second and fifth flexor tendons of the left forepaw of four mongrel dogs, the second flexor tendon was treated with hyaluronic acid of molecular weight 3.6 x 10(6) daltons applied topically between the synovial sheath and the repair site. The left forepaws were completely immobilized for 5 weeks to optimize the formation of adhesion ingrowth. After death, the repaired tendons and sheaths were removed en bloc, fixed, and dissected. Gross inspection and histologic evaluation of all tendons showed that the quality and quantity of adhesions from the wound repair to the synovial sheath appeared to have been consistently affected by hyaluronan. Hyaluronic acid had a beneficial effect on both the repair site and synovial sheath by decreasing the peripheral inflammatory response and promoting a contact healing process via epitenon and endotenon cell involvement in the repair process.     

Prevention of restrictive adhesions in primary tendon repair by HA-membrane: experimental research in chickens.

Hyaluronic acid (HA) is a glycosaminoglycan polymer that has been found to have some beneficial effects on the prevention of adhesions in primary tendon repairs. The need for slow elimination preparations of HA has been identified. We have combined HA and carboxymethylcellulose (CMC) in order to get a slow elimination preparation of HA and studied its possible effect on primary tendon healing. A gel form of NaHe (19 mg/ml; mw: 6.5 x 10(6)) was mixed with Na CMC (degree of substitution: 0.8) under sterile conditions. A jelly like mixture was thinned and HA membrane was achieved after drying in the refrigerator. The right legs of Leghorn chickens (n = 30) were prepared under IM ketamine anaesthesia by making partial cuts (75%) of flexor profundus tendons at zone II in the second, third and fourth toes, and repaired using a modified Kessler type suture (5/0 nylon). HA-membranes were applied around the repair sites in the third toes while 0.5 ml of hyaluronic acid and saline were poured on to the repair sites in the second and fourth toes, respectively. Skin incisions were closed and the legs were splinted for 15 days. Biomechanical and histological controls were made at the first, second and third postoperative months. No wound dehiscence or exposure of repaired tendons was observed on the operated toes. After collection of samples by amputation at MP levels, two-phalanx free biomechanical assessment was done. The calculated peaks of differential joint motion were very similar to the corresponding non-operated contralateral toes in the HA-membrane treated group. The toe tip displacement curves also resembled the non-operated ones in this group. HA membrane was detected as blue particles on specimens taken at the 30th day following surgery. There were few adhesions in this group microscopically at the third month. Adhesions were similar in the HA treated group while dense adhesions were seen in the saline treated group. These findings suggest that HA membrane acting as a physicochemical barrier can prevent restrictive adhesions in primary tendon repairs.     

Hyaluronic acid and its effect on postoperative adhesions in the rabbit flexor tendon. A preliminary look

The effect of hyaluronic acid in preventing adhesion formation in a surgically prepared rabbit flexor tendon model has been evaluated. Nineteen rabbits had partial tenotomy of the middle digit flexor profundus tendon, eight being treated with hyaluronic acid and eleven with saline. The quality of tendon repair and the quantity of adhesion tissue were graded. Though both the treated and control groups showed significant adhesions, the hyaluronic acid treated tendons showed less adhesion tissue and better sliding properties as compared to the controls. No significant difference was noted in the quality of tendon repair and no adverse effects of hyaluronic acid were seen. It is proposed that additional investigation into the development of a better model of postoperative tendon adhesions and an improved characterization of this model are needed. This preliminary study suggests that hyaluronic acid is effective in reducing the quantity of adhesions after tendon surgery but warrants further evaluation.     

Effects of corticosteroids and hyaluronic acid on torn rotator cuff tendons in vitro and in rats

Corticosteroids (CS) or hyaluronic acid (HA) is used in subacromial injection for the conservative treatment of rotator cuff tears (RCT); this study addresses the question of how CS and HA affect the tendon tissue and fibroblasts in vitro and in rats. Cell proliferation assays were performed in human tendon fibroblasts from RCT. Rats underwent surgery to create RCT, and the surgical sites were injected with CS or HA. The rotator cuff tendons were subjected to biomechanical testing, microscopic and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and ultrastructural analysis. Cell proliferation was significantly decreased with CS in vitro (p < 0.05). Maximal load of CS‐treated tendons was significantly decreased compared with that of HA‐treated tendons (p < 0.05), as well as PCNA⁺ cells at 2 weeks (p < 0.05). Ultrastructural observations of the CS‐treated rats detected apoptosis of tendon fibroblasts 24 h after surgery. Histological and biomechanical data 4 weeks after surgery were not significant among the three groups. Unlike HA, CS caused cell death, and inhibition of the proliferation of tendon fibroblasts, leading to a delay of tendon healing involved and a subsequent decrease of biomechanical strength at the surgical site. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1523–1530, 2015.     

The effect of ultrasound on the healing of repaired cockerel tendon: Is collagen crosslinkage a factor?

The acid solubility of the collagen of cockerel tendon demonstrates a similar degree of intermolecular acid-labile cross-linkage to that found in adult human tendon, implying similar maturity of the collagen. By contrast, rabbit tendon collagen demonstrates a dissimilar degree of cross-linkage suggesting immaturity of the collagen. Since this cross-linkage is likely to be related to mechanical properties, the cockerel may well be a better animal model than the rabbit for the study of tendon healing. The application of ultrasound to sutured cockerel tendons produced no change in the mechanical strength of the tendon at six weeks, or its propensity to form adhesions, relative to untreated control sutured tendons. This contrasts with the decrease in strength after ultrasound found by previous workers using rabbits.     

CORR® ORS Richard A. Brand Award for Outstanding Orthopaedic Research: Engineering Flexor Tendon Repair With Lubricant,Cells, and Cytokines in a Canine Model

Background

Adhesions and poor healing are complications of flexor tendon repair.

Questions/purposes

The purpose of this study was to investigate a tissue engineering approach to improve functional outcomes after flexor tendon repair in a canine model.

Methods

Flexor digitorum profundus tendons were lacerated and repaired in 60 dogs that were followed for 10, 21, or 42 days. One randomly selected repair from either the second or fifth digit in one paw in each dog was treated with carbodiimide-derivatized hyaluronic acid, gelatin, and lubricin plus autologous bone marrow stromal cells stimulated with growth and differentiation factor 5; control repair tendons were not treated. Digits were analyzed by adhesion score, work of flexion, tendon-pulley friction, failure force, and histology.

Results

In the control group, 35 of 52 control tendons had adhesions, whereas 19 of 49 treated tendons had adhesions. The number of repaired tendons with adhesions in the control group was greater than the number in the treated group at all three times (p = 0.005). The normalized work of flexion in treated tendons was 0.28 (± 0.08), 0.29 (± 0.19), and 0.32 (± 0.22) N/mm/° at Day 10, Day 21, and Day 42 respectively, compared with the untreated tendons of 0.46 (± 0.19) at Day 10 (effect size, 1.5; p = 0.01), 0.77 (± 0.49) at Day 21 (effect size, 1.4; p < 0.001), and 1.17 (± 0.82) N/mm/° at Day 42 (effect size, 1.6; p < 0.001). The friction data were comparable to the work of flexion data at all times. The repaired tendon failure force in the untreated group at 42 days was 70.2 N (± 8.77), which was greater than the treated tendons 44.7 N (± 8.53) (effect size, 1.9; p < 0.001). Histologically, treated repairs had a smooth surface with intrinsic healing, whereas control repairs had surface adhesions and extrinsic healing.

Conclusions

Our study provides evidence that tissue engineering coupled with restoration of tendon gliding can improve the quality of tendon healing in a large animal in vivo model.

Clinical Relevance

Tissue engineering may enhance intrinsic tendon healing and thus improve the functional outcomes of flexor tendon repair.     

Reducing friction by chemically modifying the surface of extrasynovial tendon grafts.

In this study we evaluated methods to reduce the friction of an extrasynovial tendon under a pulley in vitro. The surface of canine peroneus longus (PL) tendons was modified with gelatin and/or hyaluronic acid (HA) under different conditions. The gliding resistance between treated or control tendons and the canine digital flexor pulley was measured during 500 cycles of simulated flexion/extension. After 500 cycles, the gliding resistance of normal PL tendon increased 10-fold (p<0.05), while the gliding resistance of tendons coated with carbodiimide derivatized gelatin (cd-gelatin) or carbodiimide derivatized gelatin/HA (cd-gelatin-HA) did not increase significantly. The PL tendon treated with cd-gelatin-HA had a similar friction response during the repetitive motion as the intrasynovial flexor digitorum profundus (FDP) tendon. Scanning electron microscopy after 500 cycles of motion showed that the tendon surface in the group treated with cd-gelatin-HA appeared smoother than tendons in the other groups.     

Surface treatment of flexor tendon autografts with carbodiimide-derivatized hyaluronic Acid. An in vivo canine model

BACKGROUND: Clinical and experimental studies have demonstrated that restrictive adhesions and poor digital motion are common complications after extrasynovial tendon grafting in an intrasynovial environment. The purpose of this study was to test the hypothesis that surface modification of an extrasynovial tendon with use of a carbodiimide-derivatized hyaluronic acid-gelatin polymer (cd-HA) improves gliding ability and digital function after tendon grafting in a canine model in vivo. METHODS: The peroneus longus tendons from both hindpaws of twenty-four dogs were harvested and transplanted to replace the flexor digitorum profundus tendons in the second and fifth digits of one forepaw. Prior to grafting, one of the peroneus longus tendons was coated with cd-HA, which consists of 1% hyaluronic acid, 10% gelatin, 0.25% 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), and 0.25% N-hydroxysuccinimide (NHS), while the other was immersed in saline solution only. Eight dogs were killed at one, three, and six weeks. Digital normalized work of flexion, tendon gliding resistance, and hyaluronic acid quantification (with the hyaluronic acid-binding-protein staining technique) were the outcome measures. RESULTS: The normalized work of flexion of the tendons treated with cd-HA was significantly lower than that of the saline-solution-treated controls at each time-point (p < 0.05). The gliding resistance of the cd-HA group was significantly lower than that of the saline-solution group at three and six weeks (p < 0.05). The ratio between the intensity of staining of the cd-HA-treated tendons with that of the saline-solution-treated controls was significantly greater at time-0 than at three or six weeks (p < 0.05), but there was no significant difference between time-0 and one-week values. CONCLUSIONS: Treating the surface of an extrasynovial tendon autograft with a carbodiimide-derivatized hyaluronic acid-gelatin polymer decreases digital work of flexion and tendon gliding resistance in this flexor tendon graft model in vivo. CLINICAL RELEVANCE: cd-HA gelatin may provide surgeons with a new and useful method to improve the quality of tendon graft surgery.     

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.     

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     

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.     

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     

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.     

Flexor tendon biology

Significant advances in the understanding of intrasynovial flexor tendon repair and rehabilitation have been made since the early 1970s. The concept of adhesion-free, or primary tendon healing--that tendons could heal intrinsically without the ingrowth of fibrous adhesions from the surrounding sheath has been validated both experimentally and clinically in studies over the past 25 years. Recent attempts to understand and improve the results of intrasynovial flexor tendon repair have focused upon restoration of the gliding surface, augmentation of early post-operative repair site biomechanical strength and on the elucidation of the molecular biology of early post-operative tendon healing. The goals of the surgical treatment of patients with intrasynovial flexor tendon lacerations remain unchanged: to achieve a primary tendon repair of sufficient tensile strength to allow application of a post-operative mobilization rehabilitation protocol. This program should inhibit the formation of intrasynovial adhesions and restore the gliding surface, while facilitating the healing of the repair site.     

Comparison of postoperative early active mobilization and immobilization in vivo utilising a four-strand flexor tendon repair

We evaluated a technique of four-strand double-modified locking Kessler flexor tendon repair in healing tendons. Seventy-two canine flexor digitorum profundus tendons in Zone 2 were repaired and evaluated following either active mobilization or immobilization at 0, 7, 14, 28 and 42 days after surgery. Fifty-six tendons were examined for gap and ultimate strength using a tensile testing machine and 16 were evaluated with standard hematoxylin and eosin, and Masson's trichrome staining. All tendons healed without rupture or gap formation of more than 1 mm, thus demonstrating that this repair technique has enough tensile strength to withstand early active mobilization. The gap and ultimate strength of actively mobilized tendons did not decrease significantly during the first 7 days, and were significantly greater than those of immobilized tendons throughout the 42-day study period. Actively mobilized tendons healed without the extrinsic adhesions and large tendon calluses that were found in immobilized tendons.     

The effect of carbodiimide-derivatized hyaluronic acid and gelatin surface modification on peroneus longus tendon graft in a short-term canine model in vivo

PURPOSE: We have recently reported that application of carbodiimide-derivatized hyaluronic acid and gelatin (cd-HA gelatin) to a peroneus longus tendon graft increased tendon graft gliding ability and decreased work of flexion compared with untreated grafts in a canine model in vivo. In this study, we investigated the effect of this modification on adhesions, stiffness, strength of the distal attachment, and fibroblast count. METHODS: A total of 24 dogs were used for this study. The peroneus longus tendons of each hind leg were grafted into the 2nd and 5th digits of one forepaw in each dog. One peroneus longus tendon was treated with cd-HA gelatin prior to grafting, and the other one was immersed in 0.9% saline solution as a control. Animals were killed 1, 3, or 6 weeks postoperatively. RESULTS: The adhesion score of cd-HA gelatin-treated tendons was significantly less than that in the saline-treated tendons at all time points. There was no significant difference in the indentation stiffness between HA- and saline-treated grafts at any time point. For the ultimate force at the distal attachment, there was a significant difference among the time points, with a steady increase over time, but no significant difference between treated and control tendons at any time point. There was no significant difference in fibroblast count between treated and control tendons at any time point. CONCLUSIONS: Although gross adhesion formation was less, there was no significant difference in strength at the distal tendon-bone interface, cellularity, or tendon graft stiffness when comparing saline-treated and cd-HA gelatin-treated tendon grafts in vivo.