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[Experimental single-stage reconstruction of the tendon sheath and flexor tendon (free tendon graft, using a vein for sheath on the flexor tendon in dogs)].

In dog experiments the flexor tendons of the 2nd toe together with their tendon sheaths have been extirpated by the authors. Then on the place of the tendon sheath complex-resembling the human hand's "no man's land" -for the substitution of the tendon sheath-free inautotransplants with long vein-segments have been grafted in one sitting. Resuming the results of the macroscopic and light microscopic examinations carried out in definite times it has been found by the authors that while the vein segment was revascularized in the course of one or two weeks, the regeneration of the tendon transplant was slightly retarded. Between the vein and the tendon but adhesion of medium degree were found. The possibilities of the clinical use of the method are discussed.

Animals

How Does Tendon Region, Donor, and the Presence of Disease Affect Protein Composition of the Achilles Tendon?

BACKGROUND: Response to treatment for tendinopathy is variable, which may reflect variability in underlying etiology and capacity for the tendon to respond to treatment. Understanding variability in tendon protein composition may help improve our understanding of the mechanistic underpinnings of painful tendon degeneration and inform treatment targets. QUESTIONS/PURPOSES: (1) What factors (tendon region, individual characteristics, presence of disease) contribute to protein compositional (proteomic) and structural variation in human Achilles tendons? (2) What compositional changes characterize tendinopathy, and what protein interactions might contribute to tendon degeneration? (3) How does diabetes influence tendon composition, and what mechanisms might underlie tendon dysfunction in individuals with diabetes? METHODS: In this exploratory, cross-sectional study, human Achilles tendon specimens were obtained from individuals with (diabetes group, n = 5) or without diabetes (control group, n = 5) undergoing lower extremity amputation and from individuals undergoing tendon debridement surgeries for tendinopathy (tendinopathy group, n = 8). Specimens were collected between 2019 and 2023. Protein abundances were quantified and analyzed using mass spectrometry, hierarchical clustering, and principal component analysis. To evaluate the role of tendon region and donor on tendon protein compositional variability, we assessed proteomic differences between three regions in nontendinopathic tendons from three individuals. To identify the contribution of disease (that is, presence of tendinopathy or diabetes) on protein composition, we compared tendons from the tendinopathy (n = 8 [2 males, 6 females], mean &#xb1; SD age 48 &#xb1; 11 years), diabetes (n = 5 [3 males, 2 females], age 54 &#xb1; 9 years), and control (n = 5 [3 males, 2 females], age 42 &#xb1; 12 years) groups. Proteomic differences associated with tendinopathy and diabetes were further examined using functional enrichment and protein-protein interaction network analysis. RESULTS: Variability in tendon protein composition was primarily from presence of disease, followed by donor and then tendon region. Protein composition distinguished tendons with tendinopathy from controls, with 311 proteins differentially expressed (152 overexpressed and 159 underexpressed; fold change &#x2265; 1.5, p < 0.05) and higher Bonar scores indicating greater degeneration (mean &#xb1; SD Bonar score tendinopathy group 8.6 &#xb1; 1.2 versus control group 2.1 &#xb1; 0.7; p = 0.01). Pathway analysis identified dysregulation in extracellular matrix remodeling (TIMP1, MMP3, MMP10), inflammatory response (TNF-&#x3b1;, EGFR1), and metabolic reprogramming. Tendons from individuals with diabetes exhibited minimal proteomic changes compared with the control group, with 66 differentially expressed proteins (31 overexpressed and 35 underexpressed; fold change &#x2265; 1.5, p < 0.05) with no histopathologic differences between diabetes and control group tendons (mean &#xb1; SD Bonar score diabetes group 3.4 &#xb1; 1.0 versus control group 2.1 &#xb1; 0.7; p = 0.19). Tendons in the diabetes group showed reductions in Type I collagen, enrichment of pathways associated with fibrosis and metabolic dysfunction, and inflammatory pathways associated with &#x3b1; 6 &#x3b2; 4 integrin. CONCLUSION: Our findings indicate that Achilles tendon composition primarily differs based on disease etiology, with tendinopathy showing extensive extracellular matrix disruption and inflammatory activity, whereas tendons from individuals with diabetes exhibit more subtle compositional changes. This distinction suggests that tendinopathy may require targeted interventions addressing tissue remodeling and inflammation, whereas diabetes may predispose tendons to injury but not directly result in degeneration. Understanding these protein compositional variations can help refine hypotheses about disease progression, treatment response, and potential therapeutic targets. CLINICAL RELEVANCE: While proteomic analysis is not currently a part of routine clinical assessment, these findings provide a framework for identifying protein markers that may aid in early diagnosis or patient stratification to improve treatment alignment. Future studies could determine whether these proteomic changes correlate with treatment response and further inform our understanding of early-stage degeneration from chronic disease. By bridging molecular findings with clinical presentation, this study lays the groundwork for future research on precision medicine approaches for tendon disorders, with the long-term goal of tailoring treatment based on both biological and symptomatic characteristics.

Humans

[Reconstruction of the injured flexor tendon in the proximal half of the "no man's land" by a modified method (tendon sheath reconstruction using a vein graft)].

On the basis of long years' experiences the "no man's land" has been divided by the author into 2 parts: the proximal and the distal part. For the treatment of the flexor tendon lesions occurred in the distal part of the author advocates his method already published: in the "tendon sheath" formed from the vein its "bridging" by free tendon transplant. If the lesion occurred in the proximal part, the formation of a long "tendon sheath" from a vein and then its "bridging" by long tendon transplant are advocated by the author.

Adult

[Simultaneous bilateral avulsion of the quadriceps and Achilles tendons in 1 limb and of the patellar tendon in the other in a hyperparathyroid patient on chronic hemodialysis].

A case of simultaneous rupture of three tendons is reported in a patient who had suffered a bilateral nephrectomy six years earlier and was on chronic haemodialysis. The quadriceps tendon and the patellar tendon were repaired surgically. The rupture of the tendo Achillis was left untreated. Six days later a parathyroidectomy was performed; nine months later recovery was excellent. A review of the literature has been made. The role of hyperparathyroidism in the strength of the bone-tendon junction is discussed.

Achilles Tendon

Phosphopeptides and gamma-carboxyglutamic acid-containing peptides in calcified turkey tendon: their absence in uncalcified tendon.

Uncalcified samples of turkey tendon obtained prior to calcification, and other samples from areas of tendon that never calcify, contain little or no O-phosphoserine [Ser(P)], O-phosphothreonine [Thr(P)] and gamma-carboxyglutamic acid (Gla). Significant amounts of all three of these Ca2+-binding amino acids, which are found in EDTA-extractable, non-collagenous proteins, are detected coincident with the onset of mineralization of a tendon and increase in concentration as mineralization proceeds.

1-Carboxyglutamic Acid

[Results of animal experiments on alloplastic tendon replacements using the Bader tendon prosthesis].

Based on our experimental results with the Bader tendon prosthesis, encouraging results for alloplastic tendon replacement were obtained. However a general recommendation for its clinical use cannot be given. Over a period of 4-6 weeks of immobilization healing of the artificial tendon with inflammation could be observed. In the biopsies we found the equivalent of connective tissue attachment between vital tissue and the alloplastic material. We could not clarify whether this connection would endure strain. The pronounced adhesions between the anstomosis and surrounding tissue make later function questionable.

Animals

[Structure and configuration of human tendons. II. Development of tendon structure during ontogenesis].

In infants born in the 24th--30th weeks of the gravidity the praenatal development and the process of the organization of the tendinous structure have been examined by the authors. By means of photo- and polarization microscopic examinations it was found that the tendon of the flexor hand muscles (M. flexor carpi radialis, M. flexor digitorum comm.) shows mature tendinous structure earlier, than the tendons of the flexor muscles of the lower extremity (M. semitendinosus femoris, M. triceps surae). The tendons of the extensor muscles of the lower extremity (M. quadriceps femoris, M. tibialis ant.) are underdeveloped and inordinate in the foetal life--their structure develops only during the postnatal life.

Hand

Achilles tendon injury. II. Structure of tenotomized rabbit crural muscles after primary and delayed tendon suture.

This investigation was designed to study the long-term effects of surgical treatment, as recommended and followed in clinical practice, on the fine structure of rabbit crural muscles after Achilles tenotomy. Two main results were made: (A) Even after 12 weeks of mobilization a number of morphological changes were found, especially in the soleus muscles. These abnormalities were similar to those found in human soleus muscles after surgically treated Achilles tendon rupture. (B) There were a large number of small heavily stained (for myofibrillar ATPase at pH 9.4) fibres in the experimental soleus muscles, such that the normal ratio of fibre types was reversed. This was apparent if tendon suture had been performed after a delay of 3 weeks. The results suggested that as a consequence of the de- and regenerative events, induced by immobilization or tenotomy plus immobilization, a number of new fibres had been formed. Some of these were so short that they were out of reach of nerve terminals and remained non-innervated. Furthermore, from the point of view of clinical practice, the extensive long-term effects of suture delay make themselves manifest not until at least a delay of one week.

Achilles Tendon

[Ultrastructural changes in human skeletal muscles following tendon and nerve injuries. I. Ultrastructural changes following tendon injuries].

During reconstructive procedures performed 4-16 weeks after the tendon lesion the specimens obtained from the injured muscle have been examined by the authors. It was found that after the tendon injury inactivity atrophy develops and a condition of equilibrium could be observed at this time. The most important changes in the fine structure were seen in the contractile elements: these were atrophied, homogenized, fragmentated and ragged independently from the functional unities. The number of the mitochondria was considerably decreased, the sarcoplasmic reticulum was increased, and the difference between the originally red and white muscular fibres was indistinct. The glycogen content of the musculature was decreased, or it disappeared completely. No pathologic changes have been observed in the sarcolemma, the cell nuclei and the motor nerve end-organs.

Adult

Tendon transfers for radial nerve palsy: use of superficialis tendons for digital extension.

Since 1959, 22 patients have had wrist extension restored by transfer of the pronator teres to the extensor carpi radialis longus and brevis, common finger extension by transfer of the superficialis of the long finger, independent thumb and index finger extension by transfer of the superficialis of the ring finger, and abduction of the thumb by transfer of the flexor carpi radialis at the wrist joint level. Twenty-one of 22 patients have been evaluated from 8 months to 15 years after operation, with an average follow-up of 4.5 years. By our new system of evaluation, there were 10 excellent results, six good results, five fair results, and all patients improved. Sixteen patients obtained full, independent thumb-index finger extension, three had fair function, and two obtained thumb-index extension by tenodesis of the transfer. This procedure allows full metacarpophalangeal extension independent of wrist position, provides thumb-index finger extension independent of the ulnar three digits, and maintains the dorsal-radial-to-volar-ulnar plane of functional motion of the wrist by retaining the flexor carpi ulnaris.

Adolescent

Reconstruction of the canine Achilles and patellar tendons using dacron mesh silicone prosthesis. I. Clinical and biocompatibility evaluation.

Surgical replacement of the Achilles and patellar tendons using Dacron mesh silicone prostheses was performed in 15 mature beagle dogs. This part of the study includes clinical evaluation, gross inspection at autopsy of regrown tendons, and histological determination of biocompatibility of prosthetic implants. Functional continuity and integrity of prosthetic patellar tendons have been established by evaluating the biologic-prosthetic interface and the mechanical properties of regrown tendon tissue around and through the Dacron silicone replacements. Results of prosthetic Achilles tendons were less satisfactory because of difficulties in suturing to a muscle and its fascia. Although the prosthetic tendon did not regrow through the tube, it provided a structure for regrowth around it. The regrown tendons became nearly ten times the normal cross-sectional area after three to four months and decreased to two to three times after 13 months. Histological studies indicate that in the absence of infection, the Dacron mesh silicone tendon was well tolerated for periods up to 13 months. Overall results are encouraging and warrant further investigation although the regenerative capacity of human patellar and Achilles tendons is unknown.

Achilles Tendon

[Experimental tendon sheath formation by free transplantation of a long vein segment (comparative study of adhesions formed around free grafts and pedicled grafts)].

In dog experiments, in order to improve the functions after tendinous injuries diphasic operations have been performed by the authors. In the first phase, after the extirpation of the tendon of the 2nd finger its area has been bridged over by a 5-6 cm long autologous vein transplant, cannulated with a silicone rubber bar. After 4 weeks, after the vascularization of the vein transplant the silicone bar has been removed from a new approach, and through the "tunnel" formed in this way and padded with silicone a tendon has been pulled through with two different methods: 1. according to the method of Paneva-Holevitch a diphasic pedicled tendon transplant and 2. a free tendon transplant. No differences were found as regards the adhesions, the vascularization and the tissular structure of the tendon. It may be presumed that also the distal portion of the pedicled tendon transplant is really a free tendon transplant.

Animals

Transcriptomic Profiling Reveals NF-&#x3ba;B-Associated Immune Regulatory Signatures Underlying the Regenerative Effects of Hypoxia-Preconditioned Tendon Stem Cell-Derived Extracellular Vesicles.

Remodeling of the immune microenvironment is a critical determinant of tissue regeneration, yet the molecular programs associated with the enhanced therapeutic activity of hypoxia-preconditioned extracellular vesicles remain incompletely defined. In this study, we investigated the regenerative and immunomodulatory effects of hypoxia-preconditioned tendon stem cell-derived extracellular vesicles (Hypo-EVs) and employed transcriptomic profiling to identify molecular signatures associated with their biological activity. The therapeutic effects of Hypo-EVs were evaluated using a rat patellar tendon defect model and lipopolysaccharide-stimulated RAW 264.7 macrophages. Histological analysis, immunostaining, biomechanical testing, and reverse transcription-quantitative polymerase chain reaction were performed to assess tendon healing and macrophage polarization, while RNA sequencing was conducted in macrophages treated with Hypo-EVs or normoxia-derived EVs, followed by Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes pathway analyses. Hypo-EVs significantly alleviated local inflammatory responses, improved collagen organization and biomechanical properties of repaired tendons, and promoted macrophage polarization toward a reparative M2 phenotype both in&#xa0;vivo and in&#xa0;vitro. Consistent with these biological effects, transcriptomic profiling revealed extensive remodeling of inflammation-related gene expression programs, including significant suppression of NF-&#x3ba;B, TNF, IL-17, and cytokine-cytokine receptor interaction pathways. Integrative bioinformatic analyses identified an NF-&#x3ba;B-associated immune-regulatory signature that distinguished Hypo-EV-treated macrophages from those receiving normoxic EVs. Mechanistically, Hypo-EVs attenuated NF-&#x3ba;B activation, as evidenced by reduced phosphorylation of p65 and I&#x3ba;B&#x3b1;, whereas TNF-&#x3b1;-mediated NF-&#x3ba;B activation partially diminished their macrophage-repolarizing effects. Collectively, these findings demonstrate that hypoxic preconditioning enhances the immunomodulatory and regenerative functions of tendon stem cell-derived EVs. Transcriptomic analyses identified an NF-&#x3ba;B-associated immune-regulatory signature linked to the biological activity of Hypo-EVs, providing a molecular framework for understanding EV-mediated immune modulation and supporting the development of transcriptome-guided molecular signatures for regenerative therapies targeting tendon immune homeostasis.

Animals

[Spontaneous tendon ruptures of identified etiology (author's transl)].

The authors found in the material of the National Institute of Traumatology among the 650 cases of spontaneous tendon ruptures seven cases of rupture, when an identified disease localized on the tendon was the precipitating cause. Aetiology of the rupture has been as follows: tendon tuberculosis, rheumatic tendinitis xantoma tuberosum, haemangioma and pseudocyst of the tendon. In two other cases muscle biopsy revealed a concealed myopathy (central core disease and centronuclear myopathy) that may responsible for the rupture of the tendon.

Achilles Tendon

Mesenchymal Stem Cell-Derived Exosomes Combined With 3-Dimensional Hyaluronan-Based Scaffold Promote Tendon-to-Bone Tunnel Healing.

PURPOSE: Tendon-to-bone healing remains a major clinical challenge due to poor regenerative capacity at the enthesis. This study aimed to evaluate the effects of mesenchymal stem cell-derived exosomes combined with a 3-dimensional hyaluronan-based scaffold on graft healing within bone tunnels. This study was conducted in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines. METHODS: A total of 128 tendon-bone models were created in 64 Sprague-Dawley rats, randomized into four groups: control, exosome-only, scaffold-only, and exosome-loaded scaffold. At weeks 4 and 8 postoperatively, samples were analyzed histologically (hematoxylin-eosin, Masson Trichrome), immunohistochemically (fibroblast growth factor 2, bone morphogenetic protein 2), and biomechanically (maximum failure load). RESULTS: At both time points, the exosome-loaded scaffold group demonstrated significantly enhanced vascularization, cellular activity, and collagen fiber continuity and parallelism compared to all other groups (P < .05). Fibroblast growth factor 2 and bone morphogenetic protein 2 expression levels were highest in the exosome-loaded scaffold group, indicating early activation of proregenerative pathways. Biomechanically, this group also exhibited the greatest maximum failure load (15.64 &#xb1; 0.86 N at week 4; 22.97 &#xb1; 2.86 N at week 8), suggesting superior tendon-to-bone integration. The exosome-only group showed delayed but comparable improvements by week 8. CONCLUSIONS: Combining mesenchymal stem cell-derived exosomes with a 3-dimensional hyaluronan-based polycaprolactone/tricalcium phosphate scaffold enhances early and sustained healing at the tendon-bone interface. This cell-free, biocompatible strategy significantly improves vascularization, growth factor expression, collagen organization, and mechanical strength. These findings support its potential as a clinically translatable approach for improving tendon-to-bone healing outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Animals

[Investigation on the construction and spacial structure of human tendons (author's transl)].

According to their investigations there is a surface phenomen not only on the surface of intact tendons, but after longitudinal disruption it appears on spontaneously formed inside surfaces as well. The structures responsible for its production are not identical, the outside cover of the tendon is s thick, gelatinous, amorphous sheet in which a reinforcing fibersystem can be demonstrated. This latter works on a "Mädchenfänger" concept. On the arteficially exposed inside surface of a disrupted tendon the periodically striped design of small fiber groups in different layers summarizes in an oblique or transversal drawing. The authors stereomicroscopic findings need further investigations on biopsy tendons in order to determine the morphological changes in relation to tendon tension during in vivo function.

Humans

A comparison of bone matrix and tendon with particular reference to glycoprotein content.

Bone matrix and tendon are compared in terms of their carbohydrate and non-collagenous protein composition. The collagen content of both tissues was similar (90-91%), but bone matrix had at least three times as much sialic acid (0.28%) as tendon (0.08%). Smaller differences were found in the analysis of hexoses and hexosamines. After digestion with bacterial collagenase, about 9% of the total protein from both tissues was non-diffusible on dialysis, and this contained only 0.15% (bone) and 0.7% (tendon) of the original hydroxyproline; recovery of sialic acid was 86-87%. The collagenase-resistant soluble material amounted to about 9% (bone matrix) and 5% (tendon); the insoluble residues were 1 and 4% respectively. There were clear differences in the carbohydrate contents of the digests, but the amino acid compositions were similar. When the soluble digests were chromatographed on DEAE-cellulose, the elution profiles indicated the presence in each tissue of a variety of glycoproteins and a proteoglycan fraction, and showed clearly that an acidic glycoprotein corresponding to bone sialoprotein was not present in tendon.

Amino Acids