Peritendinous Adhesion Formation Research Articles

Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26RtdTomato mice to lethally irradiated Ackr1−/− mice (Ackr1−/− chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

Antiadhesion Biomaterials in Tendon Repair: Application Status and Future Prospect.

The healing process after tendon injury is often accompanied by the formation of peritendinous adhesion, contributing to limb dysfunction and exerting detrimental effects on the individuals, as well as the development of society and economy. With the continuous development of material science, as well as the augmented understanding of tendon healing and the mechanism of peritendinous adhesion formation, materials used for the fabrication of barrier membranes against peritendinous adhesion emerge endlessly. In this article, based on the analysis of the mechanism of adhesion formation, we first review the commonly used natural and synthetic materials, along with their corresponding fabrication strategies, in order to furnish valuable insights for the future optimization and development of antiperitendinous adhesion barrier membranes. This article also discusses the interaction between antiadhesion materials and cells for ameliorating peritendinous adhesion.

Unidirectional gene delivery electrospun fibrous membrane via charge repulsion for tendon repair

Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.

Full-Length Endoscopic Adhesiolysis of the Achilles Tendon and Triceps Surae

Fibrous adhesions of the Achilles tendon and triceps surae can cause calf and heel cord pain, limited ankle dorsiflexion, and even equinus deformity. The purpose of this technical note is to describe the technical details of full-length endoscopic adhesiolysis of the Achilles tendon and triceps surae. This minimally invasive approach has the advantage of allowing immediate postoperative vigorous mobilization and stretching exercise, which can reduce formation of peritendinous adhesions as compared to immobilization.

A Biomimetic Adhesive and Robust Janus Patch with Anti-Oxidative, Anti-Inflammatory, and Anti-Bacterial Activities for Tendon Repair.

Early stage oxidative stress, inflammatory response, and infection after tendon surgery are highly associated with the subsequent peritendinous adhesion formation, which may diminish the quality and function of the repaired tendon. Although various anti-inflammatory and/or antibacterial grafts have been proposed to turn the scale, most of them suffer from the uncertainty of drug-induced adverse effects, low mechanical strength, and tissue adhesiveness. Here, inspired by the tendon anatomy and pathophysiology of adhesion development, an adhesive and robust dual-layer Janus patch is developed, whose inner layer facing the operated tendon is a multifunctional electrospun hydrogel patch (MEHP), encircled further by a poly-l-lactic acid (PLLA) fibrous outer layer facing the surrounding tissue. Specifically, MEHP is prepared by gelatin methacryloyl (GelMA) and zinc oxide (ZnO) nanoparticles, which are co-electrospun first and then treated by tannic acid (TA). The inner MEHP exhibits superior mechanical performance, adhesion strength, and outstanding antioxidation, anti-inflammation, and antibacterial properties, and it can adhere to the injury site offering a favorable microenvironment for tendon regeneration. Meanwhile, the outer PLLA acts as a physical barrier that prevents extrinsic cells and tissues from invading the defect site, reducing peritendinous adhesion formation. This work presents a proof-of-concept of a drug-free graft with anisotropic adhesive and biological functions to concert the healing phases of injured tendon by alleviating incipient inflammation and oxidative damage but supporting tissue regeneration and reducing tendon adhesion in the later phase of repair and remodeling. It is envisioned that this Janus patch could offer a promising strategy for safe and efficient tendon therapy.

Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion (Adv. Healthcare Mater. 15/2023)

Drug-Grafted Polymers In article 2203078 by Huajiang Chen, Jinglei Wu, Shen Liu, and co-workers, polylactic acid (PLA)-dicumarol conjugates are synthesized by grafting the hydroxyl of dicumarol to the carboxyl of PLA through esterification, and then electrospinning them into nanofiber membranes. Dicumarol releases in response to lipase to attenuate peritendinous adhesion formation by inhibiting Cx43/TGFβ1/Smad3 signaling pathway.

Neutralization of excessive levels of active TGF-β1 reduces MSC recruitment and differentiation to mitigate peritendinous adhesion

Peritendinous adhesion formation (PAF) can substantially limit the range of motion of digits. However, the origin of myofibroblasts in PAF tissues is still unclear. In this study, we found that the concentration of active TGF-β1 and the numbers of macrophages, mesenchymal stromal cells (MSCs), and myofibroblasts in human and mouse adhesion tissues were increased. Furthermore, knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagen I and III deposition, respectively. Moreover, we found that MSCs differentiated into myofibroblasts to form adhesion tissues. Systemic injection of the TGF-β–neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and, subsequently, PAF. These results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous adhesions. An improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.

Pyrrolidine Dithiocarbamate-loaded Electrospun Membranes for Peritendinous Anti-adhesion through Inhibition of the Nuclear Factor-κB Pathway

Peritendinous adhesion is a major cause of limb dysfunction and disability in clinical practice. Numerous studies suggest that activation of nuclear factor-κB (NF-κB) pathway in macrophages could be the pivotal figure in excessive collagen synthesis and thus peritendinous adhesion formation. In this study, we assumed this pathological process could be suppressed by inhibiting NF-κB phosphorylation and nuclear translocation using pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor with the ability to penetrate cell membranes, in macrophages. Then, we conducted electrospinning process to incorporate PDTC into poly(L-lactic) acid (PLA) electrospinning membranes, that is, the PDTC-PLA membranes. Further, with integral film quality and stable drug release property, the PDTC-PLA membranes were subsequently analyzed in the capability and mechanism of preventing adhesion formation both in vitro and in vivo. Our results showed inhibition of macrophage proliferation as well as NF-κB pathway activation from in vitro assays and outstanding promotion in inhibiting NF-κB p65 phosphorylation and reducing adhesion formation from in vivo assays of PDTC-PLA compared to PLA membranes. In conclusion, our findings suggested that PDTC-PLA as an alternative therapeutic approach alleviated inflammation and peritendinous adhesion formation through NF-κB signaling pathway. Statement of significancePyrrolidine dithiocarbamate (PDTC) can be blended into poly-L-lactic acid (PLA) fibrous membranes by electrospinning process. This incorporation of PDTC into PLA is an effective way to inhibit proinflammatory activation of macrophages and to achieve advanced anti-adhesion outcome after tendon repair.

Novel enzyme-sensitive poly-tioxolone membranes for peritendinous anti-adhesion

Posttraumatic peritendinous adhesions cause limb disability, for which no proven effective treatment is available in the clinic. Physical barriers or anti-adhesion medicine was respectively used for treatment, but finding a right combined anti-adhesion way may lead to a better outcome. Electrospun anti-adhesion membranes are widely used as physical barriers, however, without ability of inhibition of adhesion formation, while the role of tioxolone in adhesion needs investigation. In this study, we incorporated poly-tioxolone into an electrospun membrane and investigated its anti-adhesion effects and associated molecular pathway. The results showed that the polymerized tioxolone-loaded electrospun membrane showed an obvious enzyme-sensitive release profile. Additionally, the in vivo results showed that tioxolone not only prevented fibroblast proliferation and adhesion but also blocked peritendinous adhesion formation by inhibiting the JAK3/STAT3/CyclinD1 pathway. The histological scores of the 3% and 6% poly-tioxolone fibrous membrane groups were 2.250 ± 0.433 and 2.125 ± 0.331, which, respectively, decreased by 47.1% and 50.0% compared to the control group. More importantly, tioxolone did not significantly affect tendon healing. Thus, tioxolone may be a candidate for peritendinous adhesion with a new anti-adhesion mechanism. Furthermore, electrospun membranes loaded with poly-tioxolone may be useful as a therapeutic material for inhibiting peritendinous adhesion in patients with tendon injury.

Beeswax-inspired superhydrophobic electrospun membranes for peritendinous anti-adhesion.

Posttraumatic peritendinous adhesion leads to limb disability. Physical barrier was widely used and thus focus was paid to fabricate the hydrophobic surfaces of electrospun membrane for anti-adhesion. However, current methods are limited and complicated. In this study, beeswax (Wax)/poly-L-lactic acid (PLA) anti-adhesion membranes were fabricated by blending electrospinning of Wax and PLA. The water contact angle was tested to investigate the hydrophobicity of the surfaces. Incorporation of Wax into PLA did not destroy the micro-pores between Wax/PLA fibers. After 7-day culture, proliferation of fibroblasts on Wax/PLA anti-adhesion membranes were significantly less than that on culture dish and PLA membranes. In rat Achilles adhesion model, least histological peritendinous adhesion formation was detected on the repaired sites in the group treated with Wax/PLA membranes than PLA membranes. Consequently, blending electrospinning of Wax into PLA is an easy method to fabricate hydrophobic surface of electrospun membrane with advanced peritendinous anti-adhesion outcome.

Metformin prevents peritendinous fibrosis by inhibiting transforming growth factor-β signaling

Injury-induced peritendinous adhesion is a critical clinical problem that leads to tendon function impairment. Therefore, it is very urgent to explore potential approaches to attenuate peritendinous adhesion formation. Recently, several studies have demonstrated the biological effect of metformin in inhibiting multiple tissue fibrosis. In this study, we performed in vitro and in vivo experiments to examine whether metformin prevents injury-induced peritendinous fibrosis. We found that tendon injury induced severe fibrosis formation in rats. However, orally administered metformin significantly alleviated the fibrosis based on macroscopic and histological evaluation. Peritendinous tissue from metformin-treated rats also showed decreased expression of fibrotic genes including col1a1, col3a1, and α-smooth muscle actin (α-SMA), and inhibition of transforming growth factor (TGF)-β1 signaling. The cell counting kit (CCK)-8, flow cytometry, and 5-ethynyl-2′-deoxyuridine (EdU) staining analyses showed that treatment of NIH/3T3 fibroblasts with metformin significantly inhibited excessive cell proliferation and promoted cell apoptosis. Metformin treatment also inhibited the expression of fibrotic genes and decreased the phosphorylation of smad2/3 and extracellular signal-regulated kinase (ERK) 1/2. Furthermore, blocking AMP-activated protein kinase (AMPK) signaling abolished the inhibitory effect of metformin on fibrosis. Our findings indicate that metformin has a protective role against peritendinous tissue fibrosis and suggest its clinical use could be a promising therapeutic approach.

Effect of Local Interferon-α, Interferon-β, and 5-Fleurouracil on Repair Strength and Prevention of Peritendinous Adhesion Following Flexor Tendon Surgery in Rabbits

Background: Peritendinous adhesion is the most common complication following tendon surgery, particularly in zone 2 of the hand. Prevention of inflammation around tendon that develops following trauma and surgery can decrease tendon adhesion formation. This study evaluates the effect of some anti-inflammatory cytokines and 5-fleurouracil in prevention of peritendinous adhesion formation. Methods: Sixteen rabbits were allocated equally into 4 groups. Tendons of index and ring fingers in zone 2 of the right hind paw were cut in all animals and then repaired. In groups 1 and 2, interferon (IFN)-α and 5-fluorouracil (5-FU) were administered locally to repair sites of index and ring fingers, respectively. In groups 3 and 4, normal saline and IFN-β were locally applied to repair sites of index and ring fingers, respectively. Three weeks later, tensiometric and histopathologic evaluations were performed. Results: The force required for removing the tendon from the sheath was not different between the groups ( P, .130), but the time that was required for removal was significantly shorter in 5-FU group ( P, .049). The strength of repair was not different between the groups in terms of force and time needed for rupture ( P, .11 and .67, respectively). In histopathologic examination, normal architecture of tendon and peritendon environment was less disturbed in IFN groups, especially in IFN-β specimens. Conclusions: Local application of 5-FU significantly reduced peritendinous adhesion. Local IFN-α and β had no significant effect on prevention of peritendinous adhesion formation. Strength of the repair was not affected by these cytokines and 5-FU.

Tenorrhaphy of the Common Calcaneal Tendon in Dogs and Cats

Background: Common calcaneal tendon (CCT) is usually affected by injuries in dogs and less frequently in cats. The Achilles mechanism consists of the convergence of three distinct structures: the tendons of the gastrocnemius muscle, superficial digital flexor muscle and the common tendons of the biceps femoris, gracilis, and semitendinosus muscles. Classification of lesions is based upon their location, severity and chronicity. Clinical signs include lameness, plantigrade stance and various degrees of tarsal hyperflexion according to the injury’s severity. The purpose of this study is to report four cases of reconstruction of the common calcaneus in three dogs and a cat.Cases: Case 1. A 10-year-old male canine, Brazilian Terrier, 7.7 kg of body weight, with a 6-month history of nonweightbearing lameness of the right hind limb attended consultation. Orthopedic examination showed plantigrade stance, hyperflexion of the right tibial-tarsal joint (TTJ) and swelling with fibrous thickening of the distal portion of the CCT. Surgical tendon repair was achieved through insertion of a locking screw on the calcaneo-tibial, tenorrhaphy and suture of a titanium plate on the caudal aspect of the CCT. Case 2. A 2-year-old female mongrel canine, with 13.3 kg of body weight was presented with the complaint of chronic left hind leg lameness. The owner described trauma at the area of the hock six months prior to consultation. On orthopedic exam, severe lameness was noted, swelling with fibrous thickening of the distal portion of the common calcaneal tendon and hyperflexion of the left TTJ (plantigrade position) were visible. Tendon repair was performed in the same manner as in case 1, except that in this case a bovine pericardium graft preserved in glycerin 98% was sutured over the tendon/plate conjunction. Case 3. A 6-year-old female mongrel canine, with 18.6 kg of body weight was attended with a 22-day history of right hind limb lameness. On physical exam intermittent lameness during gait performance and non-weight-bearing position in stance were noted. The distal portion of the limb was internally rotated with plantigrade stance and discontinuity of the CCT was palpable. Tenorrhaphy was performed similarly to case 2. Case 4. A 6 kg, 3-year-old, mixed breed male feline was admitted with a wound on the CCT region for 7 days. The wound was originated after animal interaction with a stray feline. On clinical examination the animal was non-weight bearing on the right hind limb, with plantigrade posture and with a 1 cm wound on the caudal portion of the CCT with tendon exposure. Surgical repair was performed by tenorrhaphy with placement of a surgical steel plate on the caudal aspect of the CCT. A bovine pericardium graft preserved in glycerin 98% was sutured on top of the plate. The TTJ was immobilized with a type II transarticular external fixator.Discussion: Ultrasonography is the test of choice to monitor tendon healing after tenorrhaphy. At this report, this exam was crucial to determine when the calcaneal-tibial screw could be removed. Two dogs and the cat from this report received an association of plate and bovine pericardium preserved in glycerin 98%. The purpose of this association was to increase the strength of the tenorrhaphy, and the pericardium graft had also the function of reducing the formation of peritendinous adhesions. Immobilization of the TTJ has the purpose of opposing muscle forces to avoid stress at tenorrhaphy suture increasing the strength of the healed tendon allowing early weight bear while minimizing the recurrence risk and avoiding limb contracture. We chose to perform the procedure with hyperextension of the TTJ in order to promote greater relaxation of the tendon since there was need to remove large portions of calcaneal fibrous tissues of the dogs and devitalized tissue in the cat from this report. Surgical treatment of injuries of the Achilles mechanism has good prognosis in complete closed lesions treated by tenorrhaphy associated with suture of a plate, suture of bovine pericardial graft preserved in 98% glycerin, calcaneal-tibial locking screw and splint for six weeks.Keywords: Achilles tendon, rupture, calcaneo-tibial screw, locking-loop suture pattern.

Glycosaminoglycans in Tendon Physiology, Pathophysiology, and Therapy

Although glycosaminoglycans constitute a minor portion of native tissues, they play a crucial role in various physiological processes, while their abnormal expression is associated with numerous pathophysiologies. Glycosaminoglycans have become increasingly prevalent in biomaterial design for tendon repair, given their low immunogenicity and their inherent capacity to stimulate the regenerative processes, while maintaining resident cell phenotype and function. Further, their incorporation into three-dimensional scaffold conformations significantly improves their mechanical properties, while reducing the formation of peritendinous adhesions. Herein, we discuss the role of glycosaminoglycans in tendon physiology and pathophysiology and the advancements achieved to date using glycosaminoglycan-functionalized scaffolds for tendon repair and regeneration. It is evidenced that glycosaminoglycan functionalization has led to many improvements in tendon tissue engineering and it is anticipated to play a pivotal role in future reparative therapies.

History and performance of implant materials applied as peritendinous antiadhesives.

Peritendinous fibrotic adhesions after tendon surgery are still a problem up-to-date. Approaches to overcome or at least minimize adhesion formation include implantation of barrier materials, application of lubricants or combinations of materials and functionalized drugs that are controllably released and support the healing tendon to glide and achieve the full range of motion after regeneration. Although a huge amount of different materials have been experimentally tested, the optimal strategy with respect to material and method has not yet been determined. In this review, we present a historical overview of physical barriers as well as liquid agents that have been used in order to prevent peritendinous adhesion formation. The materials are divided according to their first publication into two time frames; before and after 1980. There is no claim to include all materials tested neither will the "best" material be chosen; however, we present several materials that were experimentally tested in different animal trials as well as in clinical trials in contrast to other materials that were only tested once and disappeared from the assortment of anti-adhesives; which as such is a valuable information about its applicability for this purpose.

A new TGF‐β3 controlled‐released chitosan scaffold for tissue engineering synovial sheath

The post-operative outcome of flexor tendon healing remains limited by flexor tendon adhesion that reduces joint range of motion. Despite improvement in different methods, peritendinous adhesion formation continues to present a formidable challenge. Recent studies showed that transforming growth factor-β3 (TGF-β3) may be the key factor to reducing adhesion formation in skin or tendon. In this study, we designed a novel type of tissue engineering synovial sheath containing TGF-β3, to prevent flexor tendon adhesion. First, to achieve a stable release of TGF-β3, chitosan microspheres, prepared by crosslinking-emulsion, were used for the delivery of TGF-β3. Second, a three-dimensional chitosan scaffold was prepared by lyophilization, and TGF-β3 microspheres were carefully introduced into the scaffold. Then, synovial cells were cultured and then seeded into the TGF-β3 loaded scaffold to produce TGF-β3 controlled-released tissue engineering synovial sheath. Tests clearly demonstrated that the scaffold has good structure and compatibility with cells. These results expand the feasibility of combinative strategies of controlled protein release and tissue-engineered synovial sheath formation. Application of this scaffold to tendon repair sites may help to prevent adhesion of tendon healing.

Prevention of Peritendinous Adhesions with Electrospun Ibuprofen-Loaded Poly(l-Lactic Acid)-Polyethylene Glycol Fibrous Membranes

Physical barriers are commonly used to reduce peritendinous adhesion after injury. However, the inflammatory response to surgery cannot be prevented. This study was designed to evaluate the ability of ibuprofen-loaded poly(l-lactic acid)-polyethylene glycol (PELA) diblock copolymer fibrous membranes in preventing adhesion formation and reduce inflammation. Electrospun PELA fibrous membranes underwent mechanical testing and were characterized by morphology, surface wettability, drug release, and degradation. Results of an in vitro drug release study showed that a burst release was followed by sustained release from fibrous membranes with high initial ibuprofen content. Fewer L929 mouse fibroblasts adhered to and proliferated on the ibuprofen-loaded PELA fibrous membrane compared with tissue culture plates or PELA fibrous membrane without ibuprofen. In a chicken model of flexor digitorum profundus tendon surgery, the ibuprofen-loaded PELA fibrous membranes prevented tissue adhesion and significantly reduced inflammation. Taken together, these results demonstrate that ibuprofen-loaded PELA fibrous membranes prevent peritendinous adhesion formation better than membranes that do not contain ibuprofen, through anti-adhesion and anti-inflammatory actions.

Effect of Mitomycin-C on post-operative adhesions in tendon surgery

We investigated the effect of mitomycin-C on the reduction of the formation of peritendinous fibrous adhesions after tendon repair. In 20 Wistar albino rats the tendo Achillis was cut and repaired using a modified Kessler technique. The rats were divided into two equal groups. In group 1, an injection of mitomycin-C was placed between the tendon and skin of the right leg. In group 2, an identical volume of sterile normal saline was injected on the left side in a similar fashion. All the rats received mitomycin-C or saline for four weeks starting from the day of operation. The animals were killed after 30 days. The formation of peritendinous fibrous tissue, the inflammatory reaction and tendon healing were evaluated. The tensile strength of the repaired tendons was measured biomechanically. Microscopic evidence of the formation of adhesions and inflammation was less in group 1. There was no significant difference in the tensile load required to rupture the repaired tendons in the two groups. Mitomycin-C may therefore provide a simple and inexpensive means of preventing of post-operative adhesions.

Encircling the Tendon Repair Site with Collagen-GAG Reduces the Formation of Postoperative Tendon Adhesions in a Chicken Flexor Tendon Model

Tendon healing is a complex and coordinated event involving the activation of extrinsic mechanisms as in classic reparative skin wound healing as well as intrinsic mechanisms characteristic of regenerative wound healing. Despite improvements in surgical and rehabilitative techniques, tendon adhesions remain the most frequent cause of disability following tendon surgery. In this animal model, we evaluated the use of a clinically available, biocompatible collagen- glycosaminoglycan (GAG) material as an adjunct to surgical tendon repair. Thirty-two white leghorn chickens underwent surgical tendon repair of their left second and fourth digits. Digits were randomized to study and control groups. In both groups, the long flexor tendon was divided and repaired using a modified Kessler's repair. In the study group, collagen-GAG membrane was wrapped around the repair site. Animals were immobilized with a plaster cast and sacrificed at 3 wk. Sixteen animals had their tendon repair sites histologically assessed and graded for healing and adhesion formation. Eight animals had their tendon repairs assessed for quantification of the work associated with flexion, employing a specifically designed biomechanical apparatus. Eight animals had their repair sites tested for bursting strength. Control (untreated) tendons showed fibrous tissue surrounding the repair sites with approximately 50% of the circumference of the repair site adherent to surrounding tissue elements. The mean histologic grades for control and study group were 3.1+/-0.2 and 1.9+/-0.2, respectively. The difference between mean grades for control and study group samples was statistically significant (paired t-test: P<0.01). The work of flexion (WOF) for flexion cycles 1, 2, 3, and 4 for the control group was 0.58, 0.55, 0.46, and 0.44N/mm, respectively. The study (collagen-GAG wrapped) group had WOF values 0.16, 0.14, 0.10, 0.09N/mm, and the difference between the groups was statistically significant (paired t-test, P<0.01). The mean bursting strength of repaired tendons for control and study groups were 14.3+/-1.87N and 11.5+/-1.85N, respectively. There was no significant difference in bursting strength between the groups (paired t-test, P=0.71). Collagen-GAG reduces formation of early postoperative tendon adhesions in this chicken flexor tendon repair model. Collagen-GAG wrapped tendons healed with minimal peritendinous adhesion formation and required less effort for flexion. The investing collagen-GAG membrane did not appear to interfere with either the quality or strength of healing.

Experimental and clinical evaluation of an absorbable biomaterial inducing an anti-adhesive barrier (Divide®)

We evaluated the efficacy of a biomaterial composed of oxidised regenerated cellulose (Divide) in decreasing the formation of peri-tendinous adhesions in an experimental and clinical study. The experimental study was carried out in 47 New Zealand white rabbits whose Achilles tendons were subjected to a crush injury. The left Achilles tendon served as a control, while the right tendon was wrapped in a sheet of Divide®. Six weeks later the range of motion at the ankle was measured, the tendons were histologically analysed for peri-tendinous adhesions, the tendon sheath was examined using a scanning electron microscope for determining resorption of the biomaterial and the mechanical properties evaluated. The clinical study was performed on 22 patients; 16 requiring post-traumatic extensor tenolysis and six who underwent dorsal synovectomy for rheumatoid arthritis. A sheet of Divide® was placed either between the periosteum and the tendon or around the tendon in all patients. Total active motion and grip strength was evaluated in all patients pre-operatively and at regular intervals post-operatively. The experimental study showed that ankle range of motion was similar between the control and Divide® treated groups in two rabbits, better in the Divide® group in seven rabbits and better in the control group in two rabbits. The results were not statistically significant (P ≤ 0.262) since the numbers were quite low. Histological analysis showed that the treated tendon had a better gliding surface and minimal inflammation/reaction compared to the control group. Scanning electron microscopy on the 10th post-operative day revealed the formation of a new tendon sheath in the Divide® group. The mechanical properties of both the control and experimental Achilles tendon were similar and comparable to a human tendon. The clinical study demonstrated that Divide® was completely resorbed, perfectly biocompatible and non-allergenic. The mean T.A.M. improved from 159.4° to 187.3° (P ≤ 0.074) and grip strength from −26.7 kgF to 10.7 kgF on the 84th post-op day in the extensor tenolysis group (16 digits), while mean return of function to pre-operation level was achieved at 42nd post-operative day and grip strength increased from −3.4 kgF in the immediate, post-operative period to +5.7 kgF at the 84th day in the rheumatoid arthritis group.