The current status of various preclinical therapeutic approaches for tendon repair.

Tendons are fibroblastic structures that link muscle and bone. There are two kinds of tendon injuries, including acute and chronic. Each form of injury or deterioration can result in significant pain and loss of tendon function. The recovery of tendon damage is a complex and time-consuming recovery process. Depending on the anatomical location of the tendon tissue, the clinical outcomes are not the same. The healing of the wound process is divided into three stages that overlap: inflammation, proliferation, and tissue remodeling. Furthermore, the curing tendon has a high re-tear rate. Faced with the challenges, tendon injury management is still a clinical issue that must be resolved as soon as possible. Several newer directions and breakthroughs in tendon recovery have emerged in recent years. This article describes tendon injury and summarizes recent advances in tendon recovery, along with stem cell therapy, gene therapy, Platelet-rich plasma remedy, growth factors, drug treatment, and tissue engineering. Despite the recent fast-growing research in tendon recovery treatment, still, none of them translated to the clinical setting. This review provides a detailed overview of tendon injuries and potential preclinical approaches for treating tendon injuries.

Biomechanical evaluation of the ST-knot: A new suture for flexor tendon repair.

PURPOSE: Although tendon lacerations are common, there is currently no consensus on choice of suture. Easy and fast sutures that impart enough strength to allow mobilization are needed. This study compared the ex vivo biomechanical strength (force required to create a 2 mm tendon gap) of a novel suture (ST-knot) with that of a conventional suture (double Kessler). MATERIALS AND METHODS: Forty fresh deep flexor tendons from porcine forelimbs were used. Both repaired tendon ends were mounted on standard traction jaws of an axial traction machine at an initial distance of 40 mm for all tendons. A high-definition camera was used to determine the force forming a 2 mm gap. Ten tendons in group 1 (ST-knot) and 10 in group 2 (double Kessler) were prepared with PDS 4.0 (single thread for Kessler, double thread for ST-knot). Tendons in groups 3 (ST-knot) and 4 (double Kessler) were repaired with PDS 1.0 using the same principle. RESULTS: There was no significant difference in the force required to form a 2 mm tendon gap between groups 1 and 2, and this trend was identical when using a stronger thread in groups 3 and 4. The maximum force before rupture, mode of repair failure, stress and stiffness were also comparable, with no significant differences between groups 1 and 2, or between groups 3 and 4. CONCLUSIONS: The ST-knot showed comparable results to the double-Kessler knot, whichever the thread used. Because it involves fewer steps than conventional techniques and is easy to perform, the ST-knot may offer a therapeutic solution, particularly in complex trauma with multiple tendon injury.

Applications of ultrasound elastography to hand and upper limb disorders.

Ultrasound elastography is a recently developed method for accurate measurement of soft tissue stiffness in addition to the clinician's subjective evaluation. The present review briefly describes the ultrasound elastography techniques and outlines clinical applications for tendon, muscle, nerve, skin and other soft tissues of the hand and upper limb. Strain elastography provides a qualitative evaluation of the stiffness, and shear-wave elastography generates quantitative elastograms superimposed on a B-mode image. The stiffness in degenerative tendinopathy and/or tendon injury was significantly lower than in a normal tendon in several studies. Elastography is also a reliable method to evaluate functional muscle activity, compared to conventional surface electromyography. The median nerve is consistently stiffer in patients with carpal tunnel syndrome than in healthy subjects, on whatever ultrasound elastography technique. Elastography distinguishes normal skin from scars and can be used to evaluate scar severity and treatment. Elastography has huge clinical applications in musculoskeletal tissues. Continued development of systems and increased training of clinicians will expand our knowledge of elastography and its clinical applications in the future.

Chronological Changes in the Expression and Localization of Sox9 between Achilles Tendon Injury and Functional Recovery in Mice.

Tendons help transmit forces from the skeletal muscles and bones. However, tendons have inferior regenerative ability compared to muscles. Despite studies on the regeneration of muscles and bone tissue, only a few have focused on tendinous tissue regeneration, especially tendon regeneration. Sex-determining region Y-box transcription factor 9 (Sox9) is an SRY-related transcription factor with a DNA-binding domain and is an important control factor for cartilage formation. Sox9 is critical to the early-to-middle stages of tendon development. However, how Sox9 participates in the healing process after tendon injury is unclear. We hypothesized that Sox9 is expressed in damaged tendons and is crucially involved in restoring tendon functions. We constructed a mouse model of an Achilles tendon injury by performing a 0.3 mm wide partial excision in the Achilles tendon of mice, and chronologically evaluated the function restoration and localization of the Sox9 expressed in the damaged sites. The results reveal that Sox9 was expressed simultaneously with the formation of the pre-structure of the epitenon, an essential part of the tendinous tissue, indicating that its expression is linked to the functional restoration of tendons. Lineage tracing for Sox9 expressed during tendon restoration revealed the tendon restoration involvement of cells that switched into Sox9-expressing cells after tendon injury. The stem cells involved in tendon regeneration may begin to express Sox9 after injury.

Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse.

To better understand the molecular mechanisms of tendon healing, we investigated the Murphy Roth's Large (MRL) mouse, which is considered a model of mammalian tissue regeneration. We show that compared to C57Bl/6J (C57) mice, injured MRL tendons have reduced fibrotic adhesions and cellular proliferation, with accelerated improvements in biomechanical properties. RNA-seq analysis revealed that differentially expressed genes in the C57 healing tendon at 7 days post injury were functionally linked to fibrosis, immune system signaling and extracellular matrix (ECM) organization, while the differentially expressed genes in the MRL injured tendon were dominated by cell cycle pathways. These gene expression changes were associated with increased α-SMA+ myofibroblast and F4/80+ macrophage activation and abundant BCL-2 expression in the C57 injured tendons. Transcriptional analysis of upstream regulators using Ingenuity Pathway Analysis showed positive enrichment of TGFB1 in both C57 and MRL healing tendons, but with different downstream transcriptional effects. MRL tendons exhibited of cell cycle regulatory genes, with negative enrichment of the cell senescence-related regulators, compared to the positively-enriched inflammatory and fibrotic (ECM organization) pathways in the C57 tendons. Serum cytokine analysis revealed decreased levels of circulating senescence-associated circulatory proteins in response to injury in the MRL mice compared to the C57 mice. These data collectively demonstrate altered TGFB1 regulated inflammatory, fibrosis, and cell cycle pathways in flexor tendon repair in MRL mice, and could give cues to improved tendon healing.

Assessment of Functional Conservative Treatment of Acute Complete Achilles Tendon Rupture.

BACKGROUND: In recent years, treatment for Achilles tendon rupture (ATR) went through radical changes: from the conservative non-weight bearing approach to a functional protocol. This functional protocol allows complete weight bearing after only 2 weeks by placing the foot in a plastic boot in tapered down equines and using interchangeable wedges under the heel. This change of approach has dramatically lowered the rate of re-rupture. OBJECTIVES: To describe our preliminary results with this functional protocol and to assess outcome measures in the functional conservative treatment. METHODS: The study comprised 15 people who were evaluated clinically and by sonograph. We measured calf circumference, ankle joint range of motion (ROM), and single-leg heel-rise test (SLHRT). In addition, standard scoring methods (Achilles Tendon Rupture Score and Physical Activity Scale) were examined. RESULTS: In our cohort 14 people successfully gained SLHRT. The mean Achilles Tendon Rupture Score functional questionnaire and Physical Activity Scale physical activity questionnaire score was 85.6 of 100, and 4.7 of 6, respectively. There were no significant differences in ankle ROM compared to the uninjured limb. There was statistically significant reduction in the calf circumference and soleus muscle thickness sonographically. CONCLUSIONS: It seems that the conservative functional treatment of ATR demonstrates good functional outcomes, with the patients returning to close to normal activity, although noted muscle wasting and weakness. This protocol presents a true alternative to surgery and should be considered for most non-insertional Achilles tendon tears.

Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture.

Tendon self-renewal is a rare occurrence because of the poor vascularization of this tissue; therefore, reconstructive surgery using autologous tendon is often performed in severe injury cases. However, the post-surgery re-injury rate is relatively high, and the collection of autologous tendons leads to muscle weakness, resulting in prolonged rehabilitation. Here, we introduce an induced pluripotent stem cell (iPSC)-based technology to develop a therapeutic option for tendon injury. First, we derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in vertebrate embryos. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSC-derived tenocytes. We demonstrated that iPSC-tenocyte grafting contributed to motor function recovery after Achilles tendon injury in rats via engraftment and paracrine effects. The biomechanical strength of regenerated tendons was comparable to that of healthy tendons. We suggest that iPSC-tenocytes will provide a therapeutic option for tendon injury.

Duration of immobilisation after Achilles tendon rupture repair by open surgery: a retrospective cohort study.

BACKGROUND: The best treatment for acute Achilles tendon ruptures remains controversial. No cohort studies have compared different immobilisation durations after open surgery. This retrospective cohort study aimed to determine the optimal duration of immobilisation after this surgery. METHODS: A total of 266 patients with acute Achilles tendon rupture were divided into 4 groups (A, B, C, and D) according to immobilisation duration of 0, 2, 4, and 6 weeks, respectively. All patients underwent the same suture technique with a similar rehabilitation protocol and were examined clinically at 2, 4, 6, 8, 10, 12, 14, 16, 24, and 48 weeks, with a final follow-up at a mean of 22.3 months postoperatively. The primary outcome was the time of return to light sports activity (LSA). Secondary outcomes included range of motion (ROM) and single-legged heel rise height (SHRH). Data on operation time, complications, visual analogue pain scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, and Achilles tendon Total Rupture score (ATRS) were also collected. Demographic baseline data were analysed using one-way analysis of variance; outcome parameters were analysed using Kruskal-Wallis H test, and complications were analysed using Fisher's exact test. Statistical significance was considered at P ≤ 0.05. RESULTS: VAS scores decreased significantly, reaching 0 in all groups after 12 weeks. The AOFAS and ATRS scores were significantly different between the groups from weeks 2 to 12 (P<0.001) and weeks 2 to 16 (P<0.001), respectively. All the mean scores showed better results in group B than in the other groups. In terms of recovery time of ROM, SHRH, and LSA, groups A and B were significantly faster than groups C and D (P<0.001). There were 13 (13/266, 4.9%) complications: 5 superficial infections, 3 deep venous thrombosis, and 5 trauma-related re-ruptures. On the last follow-up, all complications had recovered. There were no significant differences in complications between the groups. CONCLUSIONS: Immobilisation for 2 weeks after this open surgery is the best choice for early rehabilitation and weight-bearing while minimising pain and other complications.

Effect of storage and preconditioning of healing rat Achilles tendon on structural and mechanical properties.

Tendon tissue storage and preconditioning are often used in biomechanical experiments and whether this generates alterations in tissue properties is essential to know. The effect of storage and preconditioning on dense connective tissues, like tendons, is fairly understood. However, healing tendons are unlike and contain a loose connective tissue. Therefore, we investigated if storage of healing tendons in the fridge or freezer changed the mechanical properties compared to fresh tendons, using a pull-to-failure or a creep test. Tissue morphology and cell viability were also evaluated. Additionally, two preconditioning levels were tested. Rats underwent Achilles tendon transection and were euthanized 12 days postoperatively. Statistical analyzes were done with one-way ANOVA or Student's t-test. Tissue force and stress were unaltered by storage and preconditioning compared to fresh samples, while high preconditioning increased the stiffness and modulus (p ≤ 0.007). Furthermore, both storage conditions did not modify the viscoelastic properties of the healing tendon, but altered transverse area, gap length, and water content. Cell viability was reduced after freezing. In conclusion, preconditioning on healing tissues can introduce mechanical data bias when having extensive tissue strength diversity. Storage can be used before biomechanical testing if structural properties are measured on the day of testing.

Partial Distal Biceps Avulsion Results in a Significant Loss of Supination Force.

BACKGROUND: Partial avulsions of the short and/or long head of the distal biceps tendon cause pain and loss of strength. The goal of the present study was to quantify the loss of supination and flexion strength following a series of surgical releases designed to simulate partial and complete short and long head traumatic avulsions. METHODS: Mechanical testing was performed to measure supination moment arms and flexion force efficiency on 18 adult fresh-frozen specimens in pronation, neutral, and supination. The distal biceps footprint length was divided into 4 equal segments. In 9 specimens (the distal-first group), the tendon was partially cut starting distally by releasing 25%, 50%, and 75% of the insertion site. In the other 9 specimens (the proximal-first group), the releases started proximally. Mechanical testing was performed before and after each release. RESULTS: Significant decreases in the supination moment arm occurred after a 75% release in the distal-first release group; the decrease was 24% in pronation (p = 0.003) and 10% in neutral (p = 0.043). No significant differences in the supination moment arm (p ≥ 0.079) or in flexion force efficiency (p ≥ 0.058) occurred in the proximal-first group. CONCLUSIONS: A simulated complete short head avulsion significantly decreased the supination moment arm and therefore supination strength. CLINICAL RELEVANCE: A mechanical case can be made for repair of partial distal biceps tendon avulsions when the rupture involves ≥75% of the distal insertion site.

Liquid Poly-N-acetyl Glucosamine (sNAG) Improves Achilles Tendon Healing in a Rat Model.

The Achilles tendon, while the strongest and largest tendon in the body, is frequently injured. Even after surgical repair, patients risk re-rupture and long-term deficits in function. Poly-N-acetyl glucosamine (sNAG) polymer has been shown to increase the rate of healing of venous leg ulcers, and use of this material improved tendon-to-bone healing in a rat model of rotator cuff injury. Therefore, the purpose of this study was to investigate the healing properties of liquid sNAG polymer suspension in a rat partial Achilles tear model. We hypothesized that repeated sNAG injections throughout healing would improve Achilles tendon healing as measured by improved mechanical properties and cellular morphology compared to controls. Results demonstrate that sNAG has a positive effect on rat Achilles tendon healing at three weeks after a full thickness, partial width injury. sNAG treatment led to increased quasistatic tendon stiffness, and increased tangent and secant stiffness throughout fatigue cycling protocols. Increased dynamic modulus also suggests improved viscoelastic properties with sNAG treatment. No differences were identified in histological properties. Importantly, use of this material did not have any negative effects on any measured parameter. These results support further study of this material as a minimally invasive treatment modality for tendon healing.

Superior mechanical recovery in male and female MRL/MpJ tendons is associated with a unique genetic profile.

Tendon ruptures heal by forming a mechanically inferior scar. We have shown that male Murphy Roths large (MRL/MpJ) mice exhibit improved tendon healing, suggesting that they can inform biological mechanisms that lead to effective tendon healing. As sex impacts healing, we assessed the effect of sex on tendon healing in MRL/MpJ and normal healer C57BL/6 (B6) mice and compared the associated biological environment with identify genes that may be integral to the improved healing outcome. We hypothesized that (a) male MRL/MpJ mice will heal with improved mechanical properties compared to females; and (b) that regenerative tendon healing will be associated with decreased fibrotic pathways, decreased inflammation, and increased activity of matrix metalloproteinases (MMPs). A midsubstance punch was introduced, and tendons were harvested after (a) 1 or 7 days for profiling of 84 genes; (b) 7 or 14 days for the assessment of MMP-2 and MMP-9 activity; and (c) 6 weeks for mechanical assessment. MRL/MpJ tendons healed with the better restoration of mechanical properties than B6 tendons. Sex did not affect the mechanical properties of healing B6 or MRL/MpJ tendons. Comparison of the gene expression profiles in the context of the mechanical outcome revealed several differences between MRL/MpJ and B6 tendon healing, including, lower inflammation, an earlier higher expression of TGF-ß-related genes that diminish by 7 days, and genes associated with enhanced cell migration in MRL/MpJ in comparison to B6 tendons. We expect that the timecourse and expression levels of these genes in scarless MRL/MpJ tendon healing represent the balanced environment that leads to improved tendon healing.

Tendon Multiscale Structure, Mechanics, and Damage Are Affected by Osmolarity of Bath Solution.

One of the most common bath solutions used in musculoskeletal mechanical testing is phosphate buffered saline (PBS). In tendon, swelling induced by physiological PBS results in decreased tendon modulus and induces microstructural changes. It is critical to evaluate the multiscale mechanical behavior of tendon under swelling to interpret prior work and provide information to design future studies. We compared the effects of physiological PBS and 8% polyethylene glycol and saline bathing solutions on tendon multiscale tendon mechanics and damage as well as microstructure with TEM in order to understand the effect of swelling on tendon. At the tissue level, tendons in PBS had a lower modulus than SPEG samples. PBS samples also showed an increased amount of non-recoverable sliding, which is an analog for microscale damage. SPEG had a higher microscale to tissue-scale strain ratio, showing the fibrils experienced less strain attenuation. From the TEM data, we showed the fibril spacing of SPEG samples was more similar to fresh control than PBS. We concluded that swelling alters multiscale mechanics and damage in addition to tendon microstructure. Future mechanical testing should consider using SPEG as a bath solution with an osmotic pressure which preserves fresh tissue water content.

Techniques for In Vivo Measurement of Ligament and Tendon Strain: A Review.

The critical clinical and scientific insights achieved through knowledge of in vivo musculoskeletal soft tissue strains has motivated the development of relevant measurement techniques. This review provides a comprehensive summary of the key findings, limitations, and clinical impacts of these techniques to quantify musculoskeletal soft tissue strains during dynamic movements. Current technologies generally leverage three techniques to quantify in vivo strain patterns, including implantable strain sensors, virtual fibre elongation, and ultrasound. (1) Implantable strain sensors enable direct measurements of tissue strains with high accuracy and minimal artefact, but are highly invasive and current designs are not clinically viable. (2) The virtual fibre elongation method tracks the relative displacement of tissue attachments to measure strains in both deep and superficial tissues. However, the associated imaging techniques often require exposure to radiation, limit the activities that can be performed, and only quantify bone-to-bone tissue strains. (3) Ultrasound methods enable safe and non-invasive imaging of soft tissue deformation. However, ultrasound can only image superficial tissues, and measurements are confounded by out-of-plane tissue motion. Finally, all in vivo strain measurement methods are limited in their ability to establish the slack length of musculoskeletal soft tissue structures. Despite the many challenges and limitations of these measurement techniques, knowledge of in vivo soft tissue strain has led to improved clinical treatments for many musculoskeletal pathologies including anterior cruciate ligament reconstruction, Achilles tendon repair, and total knee replacement. This review provides a comprehensive understanding of these measurement techniques and identifies the key features of in vivo strain measurement that can facilitate innovative personalized sports medicine treatment.

Bringing tendon biology to heel: Leveraging mechanisms of tendon development, healing, and regeneration to advance therapeutic strategies.

Tendons are specialized matrix-rich connective tissues that transmit forces from muscle to bone and are essential for movement. As tissues that frequently transfer large mechanical loads, tendons are commonly injured in patients of all ages. Following injury, mammalian tendons heal poorly through a slow process that forms disorganized fibrotic scar tissue with inferior biomechanical function. Current treatments are limited and patients can be left with a weaker tendon that is likely to rerupture and an increased chance of developing degenerative conditions. More effective, alternative treatments are needed. However, our current understanding of tendon biology remains limited. Here, we emphasize why expanding our knowledge of tendon development, healing, and regeneration is imperative for advancing tendon regenerative medicine. We provide a comprehensive review of the current mechanisms governing tendon development and healing and further highlight recent work in regenerative tendon models including the neonatal mouse and zebrafish. Importantly, we discuss how present and future discoveries can be applied to both augment current treatments and design novel strategies to treat tendon injuries.

Supraspinatus tendon transosseous vs anchor repair surgery: a comparative study of mechanical recovery in the rabbit.

BACKGROUND: Supraspinatus (SSP) tendon ruptures requiring surgical repair are common. Arthroscopic suture anchor fixation has gradually replaced transosseous repair in supraspinatus tendon tear. Our objective was to compare mechanical properties between transosseous and anchor supraspinatus repair in the first 6 postoperative weeks in a rabbit model. METHODS: One hundred and fifty-two rabbits had one supraspinatus tendon repaired either with an anchor suture 1 week after detachment or with transosseous sutures. Rabbits were euthanized at 0, 1, 2, 4 or 6 postoperative weeks. Experimental and contralateral tendons (304 tendons) were mechanically tested to failure. Data are expressed as percent of contralateral. RESULTS: Anchor repair had higher loads to failure compared to transosseous repair, at immediate repair (week 0, 52 ± 21% vs 25 ± 17%, respectively; p = 0.004) and at 1 postoperative week (64 ± 32% vs 28 ± 10%; p = 0.003) with no difference after 2 weeks. There was no difference in stiffness. Transosseous repairs showed higher rates of midsubstance failures compared to anchor repairs at 1 (p = 0.004) and 2 postoperative weeks (p < 0.001). Both transosseous and anchor repairs restored supraspinatus mechanical properties after 4 postoperative weeks. CONCLUSION: Anchor repair provided better initial tensile strength while transosseous repair led to a faster normalization (namely, midsubstance) of the mode of failure. Research to optimize supraspinatus repair may need to consider the advantages from both surgical approaches.

Diminishing effects of mechanical loading over time during rat Achilles tendon healing.

Mechanical loading affects tendon healing and recovery. However, our understanding about how physical loading affects recovery of viscoelastic functions, collagen production and tissue organisation is limited. The objective of this study was to investigate how different magnitudes of loading affects biomechanical and collagen properties of healing Achilles tendons over time. Achilles tendon from female Sprague Dawley rats were cut transversely and divided into two groups; normal loading (control) and reduced loading by Botox (unloading). The rats were sacrificed at 1, 2- and 4-weeks post-injury and mechanical testing (creep test and load to failure), small angle x-ray scattering (SAXS) and histological analysis were performed. The effect of unloading was primarily seen at the early time points, with inferior mechanical and collagen properties (SAXS), and reduced histological maturation of the tissue in unloaded compared to loaded tendons. However, by 4 weeks no differences remained. SAXS and histology revealed heterogeneous tissue maturation with more mature tissue at the peripheral region compared to the center of the callus. Thus, mechanical loading advances Achilles tendon biomechanical and collagen properties earlier compared to unloaded tendons, and the spatial variation in tissue maturation and collagen organization across the callus suggests important regional (mechano-) biological activities that require more investigation.

Thermal and non-thermal effects of capacitive-resistive electric transfer application on different structures of the knee: a cadaveric study.

Capacitive-resistive electric transfer therapy is used in physical rehabilitation and sports medicine to treat muscle, bone, ligament and tendon injuries. The purpose is to analyze the temperature change and transmission of electric current in superficial and deep knee tissues when applying different protocols of capacitive-resistive electric transfer therapy. Five fresh frozen cadavers (10 legs) were included in this study. Four interventions (high/low power) were performed for 5 min by a physiotherapist with experience. Dynamic movements were performed to the posterior region of the knee. Capsular, intra-articular and superficial temperature were recorded at 1-min intervals and 5 min after the treatment, using thermocouples placed with ultrasound guidance. The low-power protocols had only slight capsular and intra-capsular thermal effects, but electric current flow was observed. The high-power protocols achieved a greater increase in capsular and intra-articular temperature and a greater current flow than the low-power protocols. The information obtained in this in vitro study could serve as basic science data to hypothesize capsular and intra-articular knee recovery in living subjects. The current flow without increasing the temperature in inflammatory processes and increasing the temperature of the tissues in chronic processes with capacitive-resistive electric transfer therapy could be useful for real patients.

Relationship between tendon structure, stiffness, gait patterns and patient reported outcomes during the early stages of recovery after an Achilles tendon rupture.

After an Achilles tendon (AT) injury, the decision to return to full weightbearing for the practice of sports or strenuous activities is based on clinical features only. In this study, tendon stiffness and foot plantar pressure, as objective quantitative measures that could potentially inform clinical decision making, were repeatedly measured in 15 patients until 3 months after the AT rupture by using shear wave elastography (SWE) and wearable insoles, respectively. Meanwhile, patient reported outcomes assessing the impact on physical activity were evaluated using the Achilles Tendon Total Rupture Score (ATRS). At week-2 post-injury, stiffness of the injured tendon varied from 6.00 ± 1.62 m/s (mean ± SD) close to the rupture to 8.91 ± 2.29 m/s when measured more distally. While near complete recovery was observed in distal and middle regions at week-8, the shear wave velocity in the proximal region recovered to only 65% of the contralateral value at week-12. In a parallel pre-clinical study, the tendon stiffness measured in vivo by SWE in a rat model was found to be strongly correlated with ex vivo values of the Young's modulus, which attests to the adequacy of SWE for these measures. The insole derived assessment of the plantar pressure distribution during walking showed slight sub-optimal function of the affected foot at week-12, while the ATRS score recovered to a level of 59 ± 16. Significant correlations found between tendon stiffness, insole variables and distinct ATRS activities, suggest clinical relevance of tendon stiffness and foot plantar pressure measurements. These results illustrate how an alteration of the AT structure can impact daily activities of affected patients and show how digital biomarkers can track recovery in function over time.