Intrinsic Tendon Regeneration After Application of Purified Exosome Product: An In Vivo Study

Background: Tendons are primarily acellular, limiting their intrinsic regenerative capabilities. This limited regenerative potential contributes to delayed healing, rupture, and adhesion formation after tendon injury. Purpose: To determine if a tendon’s intrinsic regenerative potential could be improved after the application of a purified exosome product (PEP) when loaded onto a collagen scaffold. Study Design: Controlled laboratory study. Methods: An in vivo rabbit Achilles tendon model was used and consisted of 3 groups: (1) Achilles tenotomy with suture repair, (2) Achilles tenotomy with suture repair and collagen scaffold, and (3) Achilles tenotomy with suture repair and collagen scaffold loaded with PEP at 1 × 1012 exosomes/mL. Each group consisted of 15 rabbits for a total of 45 specimens. Mechanical and histologic analyses were performed at both 3 and 6 weeks. Results: The load to failure and ultimate tensile stress were found to be similar across all groups ( P ≥ .15). The tendon cross-sectional area was significantly smaller for tendons treated with PEP compared with the control groups at 6 weeks, which was primarily related to an absence of external adhesions ( P = .04). Histologic analysis confirmed these findings, demonstrating significantly lower adhesion grade both macroscopically ( P = .0006) and microscopically ( P = .0062) when tendons were treated with PEP. Immunohistochemical staining showed a greater intensity for type 1 collagen for PEP-treated tendons compared with collagen-only or control tendons. Conclusion: Mechanical and histologic results suggested that healing in the PEP-treated group favored intrinsic healing (absence of adhesions) while control animals and animals treated with collagen only healed primarily via extrinsic scar formation. Despite a smaller cross-sectional area, treated tendons had the same ultimate tensile stress. This pilot investigation shows promise for PEP as a means of effectively treating tendon injuries and enhancing intrinsic healing. Clinical Relevance: The production of a cell-free, off-the-shelf product that can promote tendon regeneration would provide a viable solution for physicians and patients to enhance tendon healing and decrease adhesions as well as shorten the time required to return to work or sports.

Ponseti treated idiopathic clubfoot - outcome predictive factors in the test of time: analysis of 500 feet followed for five to 20 years

Purpose To investigate a set of risk factors on the outcome of Ponseti treated idiopathic clubfeet (ICF). Methods This study was approved by the institutional review board. A retrospective analysis of prospectively gathered data over a 20-year period, at a single dedicated clubfoot clinic. Records of 333 consecutive infants with 500 ICF were analyzed. Initial Pirani score, number of casts, need for tenotomy, foot abduction brace compliance and functional score had been documented. The need for surgery after initial correction was the outcome measure. All children were followed by the same team throughout the study period. Descriptive statistics, chi-squared and multivariate analysis were performed. Results In total, 82 children (24%) with 119 feet (23.8%) were operated on, with 95.1% of feet being operated up to the age of nine years. There was a significant correlation between the Pirani score at presentation and the number of surgical procedures (chi-squared = 79.32; p < 0.001). Achilles tenotomy was done in 94.8% of patients. Pirani score of > 4.5 before casting was strongly associated with increased surgical risk (odds ratio = 1.95). When six to eight cast changes were needed, surgical prospect was 2.9 more, increasing to 11.9 when nine or more casts were needed. Conclusion Foot severity and number of cast changes were the strongest predictors for future surgery. Estimation of the risk of deformity recurrence after initial correction may help in tailoring a cost-effective personal treatment and follow-up protocol. Personalized focused protocol will help patients and caregivers and will reduce expenses. Level of Evidence Level II - prognostic study.

Ponseti method for treatment of idiopathic congenital talipes equinovarus at tertiary care center in India

<p class="abstract"><strong>Background:</strong> Different treatment methods were tried with variable success rates but Ponseti method of serial casting and manipulation stood apart due to better understanding of foot biomechanics and became accepted choice of treatment worldwide.</p><p class="abstract"><strong>Methods:</strong> 50 patients were enrolled in the study out of which 40 were available for final follow-up. We studied 40 cases during October 2018 to December 2020 at Government Medical College, Aurangabad. Out of 40 cases 31 were male and 9 were female. 25 were unilateral and 15 were bilateral. All cases were idiopathic. 4 inches Plaster of Paris (POP) bandages were cut into half and such 2 inches POP bandages were used for casting. Tenotomies were performed under controlled environment of Operation Theater with general anaesthesia. Number 12 surgical blade was used. Dennis-Browne splint was used for maintenance of correction.<strong></strong></p><p class="abstract"><strong>Results:</strong> Out of total 55 feet studied, 10 feet (18.18%) required tendo Achilles tenotomy and 45 feet (81.82%) were treated with casting alone. There were 8 cases of relapses (20%). All relapsed cases were treated with repeat casting as per Ponseti protocol and none of them required repeat tenotomy. Complications related to plaster were minimal and there were no incidence of rocker bottom deformity.</p><p class="abstract"><strong>Conclusions:</strong> We conclude that in a low income developing country like India where case load is very high; Ponseti method is effective, inexpensive form of treatment with minimal complications. Need for extensive soft tissue procedures vastly reduced with this method.</p>

Reconstructive surgery in recurrent deformity (clubfoot relapse)

Introduction Recurrent clubfoot deformity may be due to either an imperfect initial correction, or a natural history of a severe disease. In the later, idiopathic clubfoot is uncommon. In the review we describe reconstructive surgery in recurrent deformity of idiopathic clubfoot. Material and methods Surgery may be justified at different age and according to the type of deformity. Different surgical approaches and their indications are exposed in the article. Results After Ponseti’s method application additional surgeries may be considered in recurrent clubfoot deformity which may represent 10 to 20 % of cases: second Achilles tenotomy, postero-lateral relapse, complete antero-medial and postero-lateral relapse, transfer of the anterior tibial tendon, correction of sequelae: metatarsus varus, residual equinus, residual rotation of the calcaneopedal unit. Conclusion Idiopathic equine varus clubfoot is a frequent condition. Well-codified management should lead to extremely favorable functional results. Unfortunately, some cases lead to a recurrence of the deformity. Surgical procedures are sometimes required. The goal is to avoid as much as possible arthrodesis and secondary degenerative arthritis.

Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway

Acquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) of fibroblast growth factor receptor 3 (FGFR3) in Col2+ cells promote acquired HO development. Lineage tracing studies reveal that Col2+ cells adopt fate of lymphatic endothelial cells (LECs) instead of chondrocytes or osteoblasts during HO development. FGFR3 cKO in Prox1+ LECs causes even more aggravated HO formation. We further demonstrate that FGFR3 deficiency in LECs leads to decreased local lymphatic formation in a BMPR1a-pSmad1/5-dependent manner, which exacerbates inflammatory levels in the repaired tendon. Local administration of FGF9 in Matrigel inhibits heterotopic bone formation, which is dependent on FGFR3 expression in LECs. Here we uncover Col2+ lineage cells as an origin of lymphatic endothelium, which regulates local inflammatory microenvironment after trauma and thus influences HO development via FGFR3-BMPR1a pathway. Activation of FGFR3 in LECs may be a therapeutic strategy to inhibit acquired HO formation via increasing local lymphangiogenesis.

MRI recovery of the Achilles tendon after percutaneous tenotomy in older children

Background An observational study was conducted to evaluate the recovery of older children with relapsed congenital clubfoot who underwent an Achilles tenotomy for the second time as part of the Ponseti treatment. Methods Thirteen patients (19 feet) with congenital clubfoot underwent Achilles tenotomy where magnetic resonance images of the severed tendons were taken after 1, 3, and 6 weeks post-procedure. The participants were categorized into older children who underwent tenotomy for the first time (group A: mean, 4.9±1.8, and range, 2.8–7 years old) and older children who underwent tenotomy for a second time (group B: mean, 4.9±1.5, and range, 3–6.8 years old). The area of high signal intensity between the severed tendons on MRI scans was computed using Python programming language and compared with clinical assessment. Results Three weeks after Achilles tenotomy, groups A and B had clinically intact tendons in 9 out of 11 and 2 out of 8 feet, respectively, according to both clinical and MRI assessment. From week 1 to week 3 post-tenotomy, computational analysis showed that the mean high signal intensity area of group A decreased by 88.5±15.2%, which was significantly different (P .048 < .05) than the percent reduction of high signal intensity area of group B (69.0±24.9%). Conclusion Children who underwent Achilles tenotomy for the second time showed slower tendon recovery on the third week post-procedure. A possible reason for slower healing times may be due to the location of tenotomy in being further away from the musculotendinous junction where extrinsic healing mechanisms take place.