Supplementary Information.docx from Time-dependent ECM alterations of young tendons in response to stress relaxation—a model for the Ponseti method

The Ponseti method corrects a clubfoot by manipulation and casting which causes stress relaxation on the tendons. Here, we examined the effect of long-term stress relaxation on tendon extracellular matrix (ECM) by an (1) ex vivo stress relaxation test, (2) an in vitro tenocyte culture with stress relaxation and (3) an in vivo rabbit study. Time-dependent tendon lengthening and ECM alterations including crimp angle reduction and cleaved elastin were observed, which illustrated the mechanism of tissue lengthening behind the treatment—a material-based crimp angle reduction resulted from elastin cleavage. Additionally, in vitro and in vivo results observed restoration of these ECM alterations along with increased elastin level after 7 days of treatment, and the existence of neovascularization and inflammation, indicating the recovery and adaptation from the tendon in reaction to the treatment. Overall, this study provides the scientific background and information that helps explain the Ponseti method

Histopathological and immunohistochemical evaluation of cellular response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch for tendon repair

AbstractWe investigated endogenous tissue response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch intended for tendon repair. A sheep tendon injury model characterised by a natural history of consistent failure of healing was chosen to assess the biological potential of woven and aligned electrospun fibres to induce a reparative response. Patches were implanted into 8 female adult English Mule sheep. Significant infiltration of tendon fibroblasts was observed within the electrospun component of the patch but not within the woven component. The cellular infiltrate into the electrospun fibres was accompanied by an extensive network of new blood vessel formation. Tendon fibroblasts were the most abundant scaffold-populating cell type. CD45+, CD4+ and CD14+ cells were also present, with few foreign body giant cells. There were no local or systemic signs of excessive inflammation with normal hematology and serology for inflammatory markers three months after scaffold implantation. In conclusion, we demonstrate that an endogenous healing response can be safely induced in tendon by means of biophysical cues using a woven and electrospun patch

Histological evaluation of cellular response to a multifilament electrospun suture for tendon repair

BackgroundRotator cuff tendon repair in humans is a commonly performed procedure aimed at restoring the tendon-bone interface. Despite significant innovation of surgical techniques and suture anchor implants, only 60% of repairs heal successfully. One strategy to enhance repair is the use of bioactive sutures that provide the native tendon with biophysical cues for healing. We investigated the tissue response to a multifilament electrospun polydioxanone (PDO) suture in a sheep tendon injury model characterised by a natural history of failure of healing.Methodology and resultsEight skeletally mature English Mule sheep underwent repair with electrospun sutures. Monofilament sutures were used as a control. Three months after surgery, all tendon repairs healed, without systemic features of inflammation, signs of tumour or infection at necropsy. A mild local inflammatory reaction was seen. On histology the electrospun sutures were densely infiltrated with predominantly tendon fibroblast-like cells. In comparison, no cellular infiltration was observed in the control suture. Neovascularisation was observed within the electrospun suture, whilst none was seen in the control. Foreign body giant cells were rarely seen with either sutures.ConclusionThis study demonstrates that a tissue response can be induced in tendon with a multifilament electrospun suture with no safety concerns