Intrasynovial Flexor Tendon Research Articles

Current trends in the prevention of adhesions after zone 2 flexor tendon repair.

Treating flexor tendon injuries within the digital flexor sheath (commonly referred to as palmar hand zone 2) presents both technical and logistical challenges. Success hinges on striking a delicate balance between safeguarding the surgical repair for tendon healing and initiating early rehabilitation to mitigate the formation of tendon adhesions. Adhesions between tendon slips and between tendons and the flexor sheath impede tendon movement, leading to postoperative stiffness and functional impairment. While current approaches to flexor tendon repair prioritize maximizing tendon strength for early mobilization and adhesion prevention, factors such as pain, swelling, and patient compliance may impede postoperative rehabilitation efforts. Moreover, premature mobilization could risk repair failure, necessitating additional surgical interventions. Pharmacological agents offer a potential avenue for minimizing inflammation and reducing adhesion formation while still promoting normal tendon healing. Although some systemic and local agents have shown promising results in animal studies, their clinical efficacy remains uncertain. Limitations in these studies include the relevance of chosen animal models to human populations and the adequacy of tools and measurement techniques in accurately assessing the impact of adhesions. This article provides an overview of the clinical challenges associated with flexor tendon injuries, discusses current on- and off-label agents aimed at minimizing adhesion formation, and examines investigational models designed to study adhesion reduction after intra-synovial flexor tendon repair. Understanding the clinical problem and experimental models may serve as a catalyst for future research aimed at addressing intra-synovial tendon adhesions following zone 2 flexor tendon repair.

Intrasynovial autograft for reconstruction of chronic large rotator cuff tears in a rabbit model: biomechanical, computed tomography, and histological results

BackgroundRotator cuff (RC) tears are a common cause of shoulder dysfunction and pain, posing significant challenges for orthopedic surgeons. Grafts have been proposed as a solution to augment or bridge torn tendons, but optimal clinical outcomes are not always achieved due to poor graft integration, suboptimal mechanical properties, and immunological reactions. The aim of this study was to investigate the biomechanical, CT and histological results of RC reconstruction using an intrasynovial tendon autograft, in a chronic large tear subscapularis rabbit model.MethodsTwenty-six adult male Zealand white rabbits were used in this study. Large defects in the subscapularis tendons were produced bilaterally in 20 rabbits. After 6 weeks, secondary procedures were performed to the right shoulder of the rabbits, which were reconstructed with an intrasynovial interposition autograft (graft group). The left shoulder did not undergo any further treatment (defect group). The specimens were randomly divided into two equal time groups and underwent biomechanical testing, CT analysis, and histological evaluation at 6, and 12 weeks after reconstruction. In addition, 6 rabbits that were not operated, were used as a control group.ResultsAt 12 weeks post-repair, the graft group exhibited a significant increase in ultimate failure load compared to the defect group (p < 0.05). Furthermore, the 12-week graft group demonstrated comparable stiffness to that of the control group. CT analysis indicated no significant progression of intramuscular fat accumulation in both graft groups, in contrast to the 12-week defect group when compared to the control group. Finally, histological evaluation revealed a gradual integration of the graft with the host tissue at 12 weeks.ConclusionOur study suggests that intrasynovial flexor tendon autografts hold promise as an effective interposition graft for the reconstruction of chronic large RC tears, as they improve the biomechanical and biological properties of the repaired tendon. Nonetheless, further investigations in preclinical large animal models are warranted to validate and extrapolate these findings to human studies.

The effects of NF-κB suppression on the early healing response following intrasynovial tendon repair in a canine model.

The highly variable clinical outcomes noted after intrasynovial tendon repair have been associated with an early inflammatory response leading to the development of fibrovascular adhesions. Prior efforts to broadly suppress this inflammatory response have been largely unsuccessful. Recent studies have shown that selective inhibition ofIkappaB kinase beta(IKK-β), an upstream activator ofnuclear factor kappa-light chain enhancer of activated B cells(NF-κB) signaling, mitigates the early inflammatory response and leads to improved tendon healing outcomes. In the current study, we test the hypothesis that oral treatment with the IKK-β inhibitor ACHP (2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinenitrile an inhibitor) will modulate the postoperative inflammatory response and improve intrasynovial flexor tendon healing. To test this hypothesis, the flexor digitorum profundus tendon of 21 canines was transected and repaired within the intrasynovial region and assessed after 3 and 14 days. Histomorphometry, gene expression analyses, immunohistochemistry, and quantitative polarized light imagingwere used to examine ACHP-mediated changes. ACHP led to reduction in phosphorylated p-65, indicating that NF-κB activity was suppressed. ACHP enhanced expression of inflammation-related genes at 3 days and suppressed expression of these genes at 14 days. Histomorphometry revealed enhanced cellular proliferation and neovascularization in ACHP-treated tendons compared with time-matched controls. These findings demonstrate that ACHP effectively suppressed NF-κB signaling and modulated early inflammation, leading to increased cellular proliferation and neovascularization without stimulating the formation of fibrovascular adhesions. Together, these data suggest that ACHP treatment accelerated the inflammatory and proliferative phases of tendon healing following intrasynovial flexor tendon repair. Clinical Significance: Using a clinically relevant large-animal model, this study revealed that targeted inhibition of nuclear factor kappa-light chain enhancer of activated B cellssignaling with ACHP provides a new therapeutic strategy for enhancing the repair of sutured intrasynovial tendons.

Metabolic regulation of intrasynovial flexor tendon repair: The effects of dichloroacetate administration on early tendon healing in a canine model.

Enriched in glycolytic enzymes, paucicellular and hypovascular intrasynovial flexor tendons fail to mount an effective healing response after injury and repair. In contrast, well-vascularized extrasynovial flexor tendons possess high levels of oxidative phosphorylation (OXPHOS) enzymes and have a markedly improved healing capacity. This study was designed to compare the metabolic profiles of the two types of tendons and to evaluate the impact of metabolic reprogramming on early intrasynovial tendon healing in a clinically relevant canine model. Results showed that healthy intrasynovial tendons expressed higher levels of PDK1 and GAPDH and lower levels of SCX and IGF1 than did extrasynovial tendons. PDK1 encodes a subtype of pyruvate dehydrogenase kinase (PDK) that inhibits OXPHOS. Consistently, ATP production via glycolysis was favored in intrasynovial tendon cells whereas OXPHOS was the preferred pathway in extrasynovial tendon cells. Inhibition of glycolysis in vitro increased SCX expression in intrasynovial tendon cells. Therefore, dichloroacetate (DCA), a PDK1 inhibitor, was used in vivo to shift intrasynovial tendon ATP production from glycolysis to OXPHOS. Oral DCA administration reduced serum lactate concentration and increased acetyl-CoA content in repaired intrasynovial tendons and led to reduced TLR4 and IL1B and increased IGF1, SCX, and TGFB3 expressions in treated intrasynovial tendons compared to controls. Immunohistochemistry staining with anti-Ki67 and anti-CD31 antibodies revealed marked increases in cellularity and neovascularization in treated intrasynovial tendons. Clinical significance: The findings of this experiment indicate that improved gene expression and histological outcomes can be achieved by regulating glucose metabolism in the early stages following intrasynovial tendon repair.

The use of connective tissue growth factor mimics for flexor tendon repair.

Intrasynovial flexor tendon lacerations of the hand are clinically problematic, typically requiring operative repair and extensive rehabilitation. The small-molecule connective tissue growth factor (CTGF) mimics, oxotremorine M (Oxo-M) and 4-PPBP maleate (4-PPBP), have been shown to improve tendon healing in small animal models by stimulating the expansion and differentiation of perivascular CD146+ cells. To enhance intrasynovial flexor tendon healing, small-molecule CTGF mimics were delivered to repaired canine flexor tendons via porous sutures. In vitro studies demonstrated that Oxo-M and 4-PPBP retained their bioactivity and could be released from porous sutures in a sustained manner. However, in vivo delivery of the CTGF mimics did not improve intrasynovial tendon healing. Histologic analyses and expression of tenogenic, extracellular matrix, inflammation, and remodeling genes showed similar outcomes in treated and untreated repairs across two time points. Although in vitro experiments revealed that CTGF mimics stimulated robust responses in extrasynovial tendon cells, there was no response in intrasynovial tendon cells, explaining the lack of in vivo effects. The results of the current study indicate that therapeutic strategies for tendon repair must carefully consider the environment and cellular makeup of the particular tendon for improving the healing response.

Improving flexor tendon gliding by using the combination of carboxymethylcellulose-polyethylene oxide on murine model.

The current approach to flexor tendon injuries is complex and is no longer limited to suturing techniques. Strategies for improving hand function currently include rehabilitation protocols, appropriate suturing materials and techniques, changing the gliding surface by using lubricants and providing growth factors. One product, originally used in spinal surgery, has been shown to be effective in preventing postoperative adhesions. It is a combination of carboxymethylcellulose and polyethylene oxide-Dynavisc® (FzioMed, Inc.). The aim of the present study was to test the effect of Dynavisc® on acute injuries of the intrasynovial flexor tendons in the prevention of postoperative adhesions and the improvement of functional results. The study was performed on 20 Wistar rats distributed in two groups. The control group, represented by 10 rats, in which after the reconstruction of the flexor tendon, the peritendinous area was injected with saline solution and the study group, in which the peritendinous area was injected with a single administration of the lubricating gel, Dynavisc® (carboxymethylcellulose and polyethylene oxide). At 4 and 12 weeks, the rats were sacrificed and tissue biopsy consisted of tendon fragments and adjacent tissue. The evaluation of the results was performed by measuring the adhesion score and observing histological parameters. The presence of important adhesions was found in the control group compared with the group treated with Dynavisc®, where a supple and smooth tendon, with significantly fewer adhesions were found. The differences between the two groups were significant, thus indicating the efficiency of the lubricant in preventing adhesions. This study supported the important role of Dynavisc® in the regeneration of the tendon and the peritendinous structures, by limiting aberrant fibrous proliferation in the regeneration process and helping to build a peritendinous space.

Flexor tendon grafts for pulley reconstruction – Morphological aspects

BackgroundPulleys are crucial to convert flexor tendon excursion into angular motion at the metacarpophalangeal and interphalangeal joints. Loss of pulley function can lead to significant impairment of hand function and may require surgical reconstruction. This reconstruction can be achieved using different flexor tendons grafts, such as the intrasynovial flexor digitorum superficialis (FDS) or the extrasynovial palmaris longus (PL). However, there is limited knowledge on the micromorphology of human pulleys and the suitability of flexor tendon grafts for their reconstruction remains elusive. MethodsIn the present cadaver study A2 and A4 pulleys were compared with FDS and PL tendons by means of scanning electron microscopy (SEM), histology and immunohistochemistry. Surface morphology, core structure and vascularization of the specimens were analyzed. ResultsSEM imaging of the gliding surfaces revealed morphological differences between tendons and pulleys. Moreover, the core structure of FDS samples was characterized by bundles of individual collagen fibrils whereas PL tendons exhibited a less hierarchical microstructure. In contrast, pulleys consisted of lamellar sheets of densely packed collagen fibrils. Finally, immunohistochemical analyses revealed that the flexor tendons and pulleys contain similar numbers of CD31+ microvessels, indicating a comparable tissue vascularization. ConclusionThis study provides novel SEM and immunohistochemical insights into the micromorphology of human pulleys and flexor tendon grafts. Intrasynovial flexor tendons may be particularly suitable for pulley reconstruction and preserving the paratenon may be crucial for graft revascularization.

The Management of Partial Zone II Intrasynovial Flexor Tendon Lacerations: A Literature Review of Biomechanics, Clinical Outcomes, and Complications

Sir: We read with great interest the recent article entitled “The Management of Partial Zone II Intrasynovial Flexor Tendon Lacerations: A Literature Review of Biomechanics, Clinical Outcomes, and Complications,” by Lineberry et al.,1 published in Plastic and Reconstructive Surgery. We credit the authors for their extensive work in evaluating a large number of studies of variable methodologies, in an attempt to provide clarity on management of partial flexor tendon injuries. We agree with the authors’ conclusions that all suspected partial tendon lacerations should be explored surgically with direct visualization of the flexor tendon. However, we believe the authors are drawing conclusions from outdated research. Only four of 24 studies (16.6 percent) in this review were published after 2008. Over the past decade, there has been a dramatic evolution in flexor tendon management regarding suture material, tenorrhaphy techniques, and greater excursion on the repaired tendon postoperatively. Subsequently, we question the authors’ ability to make recommendations based on these studies, in particular, the grade (percent) of partial tendon laceration necessitating surgical repair and the type of tenorrhaphy when surgical intervention is required. Early active motion following flexor tendon repair encourages intrinsic healing and decreases adhesion formation.2 This postoperative therapy requires a strong, gap-free tenorrhaphy resisting forces up to 30 to 50 N.3,4 Gap formation within the repair is detrimental, as this correlates clinically to adhesion formation and rupture,5 especially for intrasynovial tendon injuries. Our department struggles to comprehend how a simple epitendinous-only repair in a partial flexor tendon laceration greater than 80 percent of the total tendon surface area can resist 2-mm gap formation during forces exerted during early active motion. Consequently, we conducted our own biomechanical assessment of 90 fresh porcine flexor digitorum profundus tendons. Partial lacerations of 70, 80, and 90 percent of the total tendon surface area were created with digital calipers. Thirty tendons in each partial laceration group were divided randomly into (1) no repair, (2) running epitendinous repair with 6-0 Prolene (Ethicon, Inc., Edinburgh, United Kingdom), and (3) four-strand Adelaide technique core repair with 3-0 Ethibond (Ethicon) with an epitendinous suture. Our findings support the authors’ conclusions that nonrepaired partial tendon lacerations of 90 percent have enough residual strength to resist rupture during early active motion. However, the forces creating 2-mm gap formation in partial lacerations of 80 percent (4.9 N) and 90 percent (3.8 N) are well below the requirements for early active motion. Tenorrhaphy with epitendinous sutures only increased resistance to the gapping to 25.1 N in the 80 percent and 15.9 N in the 90 percent partial laceration group. The addition of core suture significantly increased the resistance to 2-mm gap formation in both groups (p < 0.05). Results are displayed in Figure 1.Fig. 1.: A comparison of resistance to 2-mm gap formation between 70, 80, and 90 percent partial flexor digitorum profundus laceration.Up-to-date research on partial flexor tendon lacerations, as evident in this review, is rare. We have demonstrated that an epitendinous-only repair of partial tendon laceration greater than 80 percent does not provide adequate strength to prevent 2-mm gap formation during early active motion. We disagree with the authors’ conclusions and believe that partial tendon laceration greater than 80 percent should be managed similarly to a complete tendon laceration with both a core suture and an epitendinous suture. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication. Conor M. Sugrue, M.R.C.S., B.C.H., B.A.O.George Rahmani, M.R.C.S., B.C.H., B.A.O.Department of Plastic and Reconstructive SurgeryGalway University HospitalGalway, IrelandGSD CriúGalway, Ireland Jack L. Kelly, F.R.C.S.(Plast.)Department of Plastic and Reconstructive SurgeryGalway University HospitalGalway, Ireland

Prognostic factors for digital range of motion after intrasynovial flexor tendon injury and repair: Long-term follow-up on 273 patients treated with active extension-passive flexion with rubber bands

Study DesignObservational cohort study. IntroductionInvestigating prognostic factors using population-based data may be used to improve functional outcome after flexor tendon injury and repair. Purpose of the StudyThe aim of this study is to investigate the effect of concomitant nerve transection, combined flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) tendon transection and the age of the patient, on digital range of motion (ROM) more than 1 year after FDP tendon transection and repair in zone I and II. MethodsTwo hundred seventy-three patients with a total of 311 fingers admitted for FDP injury in zone I and II were treated with active extension-passive flexion with rubber bands and followed for at least 1 year. We compared outcome by evaluating digital mobility using Strickland's evaluation system. ResultsAt 12 months 72% of patients aged > 50 had fair or poor ROM compared to 17% of patients aged 0-25 years. At 24 months the results for patients aged > 50 had improved to 33% with fair or poor ROM, whereas no improvement had occurred for patients aged 0-25 (17% with fair or poor ROM). Concomitant nerve transection and FDS tendon transection had no negative effects on digital mobility. DiscussionAge above 50 was significantly associated with impaired digital ROM during the first year after flexor tendon injury and repair but not at 2 years follow-up. Concomitant nerve transection and combined transection of FDP and FDS do not affect digital mobility. ConclusionsOlder patients are likely to have a slower healing process and impaired digital ROM during the first year after surgery.

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.

Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair.

Recent growth factor, cell, and scaffold-based experimental interventions for intrasynovial flexor tendon repair have demonstrated therapeutic potential in rodent models. However, these approaches have not achieved consistent functional improvements in large animal trials due to deleterious inflammatory reactions to delivery materials and insufficient induction of targeted biological healing responses. In this study, we achieved porous suture-based sustained delivery of connective tissue growth factor (CTGF) into flexor tendons in a clinically relevant canine model. Repairs with CTGF-laden sutures were mechanically competent and did not show any evidence of adhesions or other negative inflammatory reactions based on histology, gene expression, or proteomics analyses at 14 days following repair. CTGF-laden sutures induced local cellular infiltration and a significant biological response immediately adjacent to the suture, including histological signs of angiogenesis and collagen deposition. There were no evident widespread biological effects throughout the tendon substance. There were significant differences in gene expression of the macrophage marker CD163 and anti-apoptotic factor BCL2L1; however, these differences were not corroborated by proteomics analysis. In summary, this study provided encouraging evidence of sustained delivery of biologically active CTGF from porous sutures without signs of a negative inflammatory reaction. With the development of a safe and effective method for generating a positive local biological response, future studies can explore additional methods for enhancing intrasynovial tendon repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2052-2063, 2018.

Combined Administration of ASCs and BMP-12 Promotes an M2 Macrophage Phenotype and Enhances Tendon Healing.

Outcomes after intrasynovial tendon repair are highly variable. An intense inflammatory cascade followed by a delayed healing response can cause adhesion formation and repair-site failure that severely impair the function of repaired digits. No effective remedies exist to fully address these issues. Cell- and growth factor-based therapies have been shown to modulate inflammation and improve cell proliferation and matrix synthesis and therefore are promising treatment approaches for intrasynovial tendon repair. (1) Can autologous adipose-derived mesenchymal stromal cells (ASCs) and recombinant bone morphogenetic protein-12 (rBMP-12) be effectively delivered to an intrasynovial flexor tendon repair without adverse effects? (2) Do autologous ASCs modulate the inflammatory response after intrasynovial tendon injury and repair? (3) Does the combined application of autologous ASCs and rBMP-12 modulate the proliferative and remodeling responses after intrasynovial tendon injury and repair? Sixteen 1- to 2-year-old female canines were used in this study. Autologous ASC sheets, with and without rBMP-12, were applied to the surface of sutured flexor tendons. Fourteen days after repair, the effects of treatment were determined using quantitative PCR (six per group) for the expression of genes related to macrophage phenotype or inflammation (IL-4, CD163, VEGF, NOS2, IL-1B, and IFNG), cell proliferation (CCND1), and tendon formation (SCX, TNMD, COL1A1 and COL3A1). Proteomics analysis (four per group) was performed to examine changes in tendon protein abundances. CD146 immunostaining and hematoxylin and eosin staining (four per group) were used to detect tendon stem or progenitor cells and to semiquantitatively evaluate cellularity at the tendon repair; analyses were done blinded to group. Gross inspection and cell tracing showed that autologous ASCs and rBMP-12 were delivered to the flexor tendon repair site without the deleterious effects of adhesion and repair-site gap formation. Quantitative assessment of gene and protein expression showed effects of treatment: ASC-sheet treatment modulated the postrepair inflammatory response and facilitated healing by increasing regenerative M2 macrophages (M2 marker CD204, twofold of normal, p = 0.030), inflammatory inhibitor (prostaglandin reductase 1 [PTRG1], 1.6-fold of normal, p = 0.026), and proteins involved in tendon formation (periostin [POSTN], 1.9-fold of normal, p = 0.035). Consistently, semiquantitative and qualitative evaluations of repaired tissue showed that ASC-sheet treatment reduced mononuclear cell infiltration (12% less than nontreated tendons, p = 0.021) and introduced CD146+ stem or progenitor cells to the repair site. The combined administration of ASCs and rBMP-12 further stimulated M2 macrophages by increasing IL-4 (116-fold of normal, p = 0.002) and led to the increase of M2 effector matrix metalloproteinase-12 involved in matrix remodeling (twofold of normal, p = 0.016) and reduction of a negative regulator of angiogenesis and cell migration (StAR-related lipid transfer domain protein13 [STARD13]; 84% of normal, p = 0.000), thus facilitating the proliferative stage of tendon repair. ASCs and BMP-12 accelerated the progression of healing in the proliferative stage of tendon repair. The effects of ASCs and BMP-12 on tendon functional recovery should be evaluated in future studies. The cell sheet approach is an effective, biocompatible, and surgeon-friendly approach for cell and growth factor delivery during tendon repair. Combined application of ASCs and BMP-12 may accelerate intrasynovial tendon healing while suppressing the adverse inflammatory response.

The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing.

BackgroundThe clinical outcomes following intrasynovial flexor tendon repair are highly variable. Excessive inflammation is a principal factor underlying the formation of adhesions at the repair surface and affecting matrix regeneration at the repair center that limit tendon excursion and impair tendon healing. A previous in-vitro study revealed that adipose-derived mesenchymal stromal cells (ASCs) modulate tendon fibroblast response to macrophage-induced inflammation. The goal of the current study was therefore to explore the effectiveness of autologous ASCs on the inflammatory stage of intrasynovial tendon healing in vivo using a clinically relevant animal model.MethodsZone II flexor tendon transections and suture repairs were performed in a canine model. Autologous ASC sheets were delivered to the surface of repaired tendons. Seven days after repair, the effects of ASCs on tendon healing, with a focus on the inflammatory response, were evaluated using gene expression assays, immunostaining, and histological assessments.ResultsASCs delivered via the cell sheet infiltrated the host tendon, including the repair surface and the space between the tendon ends, as viewed histologically by tracking GFP-expressing ASCs. Gene expression results demonstrated that ASCs promoted a regenerative/anti-inflammatory M2 macrophage phenotype and regulated tendon matrix remodeling. Specifically, there were significant increases in M2-stimulator (IL-4), marker (CD163 and MRC1), and effector (VEGF) gene expression in ASC-sheet treated tendons compared with nontreated tendons. When examining changes in extracellular matrix expression, tendon injury caused a significant increase in scar-associated COL3A1 expression and reductions in COL2A1 and ACAN expression. The ASC treatment effectively counteracted these changes, returning the expression levels of these genes closer to normal. Immunostaining further confirmed that ASC treatment increased CD163+ M2 cells in the repaired tendons and suppressed cell apoptosis at the repair site.ConclusionsThis study provides a novel approach for delivering ASCs with outcomes indicating potential for substantial modulation of the inflammatory environment and enhancement of tendon healing after flexor tendon repair.

The Biophysical Characteristics of Human Composite Flexor Tendon Allograft for Upper Extremity Reconstruction

Devastating volar hand injuries with significant damage to the skin and soft tissues, pulley structures and fibro-osseous sheath, flexor tendons, and volar plates pose a major problem to the reconstructive hand surgeon. Despite advances in tendon handling, operative technique, and postoperative hand rehabilitation, patients who have undergone flexor tendon reconstruction are often plagued by chronic pain, stiffness, and decreased range of motion with resultant decreased ability to work and poor quality of life. In this article, we expand the technique of human composite flexor tendon allografts (CFTAs), pioneered by Dr E.E. Peacock, Jr, which consist of both the intrasynovial and extrasynovial flexor digitorum superficialis and flexor digitorum profundus tendons and their respective fibro-osseous sheath consisting of the digital pulley structures, periosteum, and volar plates procured from cadaveric donors with the use of modern tissue processing techniques. Human cadaveric CFTAs were procured and divided into 2 groups-unprocessed CFTAs and processed CFTAs, which are cleansed and sterilized to a sterility assurance level of 10(-6). Physical length and width relationships as well as tensile strength and gliding resistance assessments were recorded pre-tissue and post-tissue processing. The histologic properties of the composite allografts were assessed before and after tissue processing. There was no significant difference with respect to physical properties of the composite allografts before or after tissue processing. The processed composite allografts demonstrated equivalent maximum load to failure and elastic modulus compared to unprocessed tendons. The gliding resistance of the composite tendon allografts was not significantly different between the 2 groups. The use of CFTAs addresses the issues of adhesion formation and lack of suitable donor material by providing a source of intrasynovial tendon in its unaltered fibro-osseous sheath without donor morbidity. This approach represents an important step toward designing an ideal material for complex flexor tendon reconstruction, which takes advantage of an intrasynovial flexor tendon in its native fibro-osseous sheath without the need for additional donor morbidity using a construct which can be engineered to have minimal tissue reactivity, negligible potential for disease transmission, and improved tendon healing properties versus standard tendon allograft.

Advances in the healing of flexor tendon injuries.

The intrasynovial flexor tendons of the hand are critical for normal hand function. Injury to these tendons can result in absent finger flexion, and a subsequent loss of overall hand function. The surgical techniques used to repair these tendons have improved in the past few decades, as have the postoperative rehabilitation protocols. In spite of these advances, intrasynovial flexor tendon repairs continue to be plagued by postoperative scar formation, which limits tendon gliding and prevents a full functional recovery. This paper describes the current challenges of flexor tendon repair, and evaluates the most recent advances and strategies for achieving an excellent functional outcome.

Platelet-Rich Plasma for Zone II Flexor Tendon Repair

Platelet-rich plasma (PRP) has shown promise in the treatment of tendinopathy, including rotator cuff and lateral epicondylitis. Here, we evaluate the effect of PRP on healing in a rabbit zone II flexor tendon model. Thirty New Zealand white rabbits underwent transection and repair of the second and fourth flexor digitorum profundus. Half of the rabbits received autologous PRP intraoperatively, while the other half underwent standard four-strand tendon repair. Tendons were examined at 2, 4, and 8weeks postoperatively. Range of motion and ultimate tensile strength were assessed on the fourth toes, while second toes underwent histologic analysis with hematoxylin and eosin, Masson Trichrome, and Picrosirius Red, for assessment of cell count, collagen content, and collagen maturity. There were no significant differences in ultimate tensile strength between treatments at 2, 4, or 8weeks. There was a trend towards lower tensile strength in the PRP group at 2weeks. There was no statistically significant difference in excursion or range of motion between PRP and control tendons. Cell counts at 4weeks were statistically significantly reduced in the PRP tendons as compared to controls. No difference in collagen content or maturity was detected. In contrast to previous studies, PRP did not significantly improve ultimate tensile strength. PRP-treated tendons exhibited trends towards reduced healing, including a significant reduction in cell counts as well as a smaller increase in collagen deposition over time as compared to controls. Further study is needed to determine the precise effect of PRP on intrasynovial flexor tendon repairs.

Repopulation of Intrasynovial Flexor Tendon Allograft with Bone Marrow Stromal Cells: AnEx VivoModel

Delayed healing is a common problem whenever tendon allografts are used for tendon or ligament reconstruction. Repopulating the allograft with host cells may accelerate tendon regeneration, but cell penetration into the allograft tendon is limited. Processing the tendon surface with slits that guide cells into the allograft substrate may improve healing. The purpose of this study was to describe a surface modification of allograft tendon that includes slits to aid cell repopulation and lubrication to enhance tendon gliding. Canine flexor digitorum profundus tendons were used for this study. Cyclic gliding resistance was measured over 1000 cycles. Tensile stiffness was assessed for normal tendon, tendon decellularized with trypsin and Triton X-100 (decellularized group), tendon decellularized and perforated with multiple slits (MS group) and tendon decellularized, perforated with slits and treated with a carbodiimide-derivatized hyaluronic acid and gelatin (cd-HA-gelatin) surface modification (MS-SM group). To assess tendon repopulation, bone marrow stromal cells (BMSCs) were used in the decellularized and MS groups. DNA concentration and histology were evaluated and compared to normal tendons and nonseeded decellularized tendons. The gliding resistance of the decellularized and MS groups was significantly higher compared with the normal group. There was no significant difference in gliding resistance between the decellularized and MS group. Gliding resistance of the normal group and MS-SM group was not significantly different. The Young's modulus was not significantly different among the four groups. The DNA concentration in the MS group was significantly lower than in normal tendons, but significantly higher than in decellularized tendons, with or without BMSCs. Viable BMSCs were found in the slits after 2 weeks in tissue culture. Tendon slits can successfully harbor BMSCs without compromising their survival and without changing tendon stiffness. Surface modification restores normal gliding function to the slit tendon. A multislit tendon reseeded with BMSCs, with a surface treatment applied to restore gliding properties, may potentially promote tendon revitalization and accelerate healing for tendon or ligament reconstruction applications.

The Impact of Suture Caliber and Core Suture Strands on Intrasynovial Flexor Tendon Repair: Not a clinical study

The Impact of Suture Caliber and Core Suture Strands on Intrasynovial Flexor Tendon Repair: Not a clinical study

Distal attachment of flexor tendon allograft: A biomechanical study of different reconstruction techniques in human cadaver hands

We compared the mechanical force of tendon-to-bone repair techniques for flexor tendon reconstruction. Thirty-six flexor digitorum profundus (FDP) tendons were divided into three groups based upon the repair technique: (1) suture/button repair using FDP tendon (Pullout button group), (2) suture bony anchor using FDP tendon (Suture anchor group), and (3) suture/button repair using FDP tendon with its bony attachment preserved (Bony attachment group). The repair failure force and stiffness were measured. The mean load to failure and stiffness in the bony attachment group were significantly higher than that in the pullout button and suture anchor groups. No significant difference was found in failure force and stiffness between the pullout button and suture anchor groups. An intrasynovial flexor tendon graft with its bony attachment has significantly improved tensile properties at the distal repair site when compared with a typical tendon-to-bone attachment with a button or suture anchor. The improvement in the tensile properties at the repair site may facilitate postoperative rehabilitation and reduce the risk of graft rupture.

The Effect of Core and Epitendinous Suture Modifications on Repair of Intrasynovial Flexor Tendons in an In Vivo Canine Model

To determine in vivo effects of modifications to core and epitendinous suture techniques in a canine intrasynovial flexor tendon repair model using clinically relevant rehabilitation. Our null hypothesis was that gap formation and rupture rates would remain consistent across repair techniques. We evaluated gap formation and rupture in 75 adult mongrel dogs that underwent repair of intrasynovial flexor tendon lacerations followed by standardized postoperative therapy. The current suture technique was a 4-0, 8-strand core suture with a purchase of 1.2 cm and a 5-0, epitendinous suture repair with a 2-mm purchase length and depth. We compared gap and failure by chi-square analysis to a historical group of in vivo repairs (n = 76) from the same canine model using 8-strand core suture repair with purchase of 0.75 cm and 6-0 epitendinous suture with a 1-mm purchase length and depth. A total of 93% of tendons (n = 70) demonstrated gapping of less than 3 mm using the current suture technique. Five percent of tendons (n = 4) had a gap of 3 mm or greater, and there was 1 repair site failure. This was significantly improved over the comparison group of historical 8-strand core repair technique, which resulted in 82% (n = 62) of repairs with a gap of less than 3 mm and 7 failures (9%). In an in vivo model, current modifications to suture techniques for intrasynovial flexor tendon repair demonstrated significant improvements in gap formation and rupture compared with a similar technique using shorter purchase lengths and shallower purchase depth. Suggested repair modifications for the treatment of zone II flexor tendon transections demonstrate improvements in gap formation and tendon rupture in vivo.