Abstract

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, to complement surgical procedures and to enhance the healing process at the injured site. In this work, an electrospun hybrid tubular scaffold was designed to mimic tissue fibrous arrangement and extracellular matrix (ECM) composition, and to be extemporaneously loaded into the inner cavity with human platelet lysate (PL), with the aim of leading to complete post-surgery functional regeneration of the tissue for functional regeneration of the osteo–tendon interface. For this purpose, pullulan (P)/chitosan (CH) based polymer solutions were enriched with hydroxyapatite nanoparticles (HP) and electrospun. The nanofibers were collected vertically along the length of the scaffold to mimic the fascicle direction of the tendon tissue. The scaffold obtained showed tendon-like mechanical performance, depending on HP content and tube size. The PL proteins were able to cross the scaffold wall, and in vitro studies have demonstrated that tenocytes and osteoblasts are able to adhere to and proliferate onto the scaffold in the presence of PL; moreover, they were also able to produce either collagen or sialoproteins, respectively—important components of ECM. These results suggest that HP and PL have a synergic effect, endorsing PL-loaded HP-doped aligned tubular scaffolds as an effective strategy to support new tissue formation in tendon-to-bone interface regeneration.

Highlights

  • Tendon pathologies are medical conditions, and include ruptures and overuse injuries with inflammatory and degenerative alterations, such as tendinopathies [1]

  • SAOS-2 used growth proliferation, and only hydroxyapatite nanoparticles (HP)-doping tially-aligned HP-doped tubular scaffolds aimed at the functional reparation of tendon lowed for wide spreading of the cells all over the scaffold surface, leading to cell confluency

  • The tubular structure, with crossAgain, the synergistic actions of platelet lysate (PL)-loading and HP-doping show up in the capability of sections in the mm range, was intended to allow for extemporary loading of hemoderivbone cells to properly proliferate onto the aligned scaffold (Figure 12, upper row) and proatives, like PL, concomitant with the surgical intervention, while performing controlled duce a well-developed extracellular matrix, here identified through sialoproteins staining and prolonged release of bioenhancer molecules to support tissue repair in the post-sur(Figure 12, bottom row), and richly decorated with extracellular vesicles

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Summary

Introduction

Tendon pathologies are medical conditions, and include ruptures and overuse injuries with inflammatory and degenerative alterations, such as tendinopathies [1]. 33 million musculoskeletal injuries have been reported per year, 50% involving tendons and ligaments. Several intrinsic factors, including body weight, nutrition, age, and genetic diseases that affect the connective tissue, could have an impact on tendon/ligament integrity. The incidence of Achilles tendon ruptures (one of the most frequently injured tendons), is up to 1%, and typically in 30–50-year-old men [2]. Chronic, nonhealing tendon injuries frequently require surgical treatment, and, despite recent advancements in orthopaedic surgery, current tendon repair techniques yield less-than-optimal results [3,4,5]. Healed tendons tend to form scar tissue with mechanical properties different as compared to healthy ones, and are prone to reinjury

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