Induced Periosteum-Mimicking Membrane with Cell Barrier and Multipotential Stromal Cell (MSC) Homing Functionalities.

Heather E Owston,Stephen J Russell,Katrina M Moisley,Peter V Giannoudis,Elena Jones,Giuseppe Tronci

doi:10.3390/ijms21155233

Abstract

The current management of critical size bone defects (CSBDs) remains challenging and requires multiple surgeries. To reduce the number of surgeries, wrapping a biodegradable fibrous membrane around the defect to contain the graft and carry biological stimulants for repair is highly desirable. Poly(ε-caprolactone) (PCL) can be utilised to realise nonwoven fibrous barrier-like structures through free surface electrospinning (FSE). Human periosteum and induced membrane (IM) samples informed the development of an FSE membrane to support platelet lysate (PL) absorption, multipotential stromal cells (MSC) growth, and the prevention of cell migration. Although thinner than IM, periosteum presented a more mature vascular system with a significantly larger blood vessel diameter. The electrospun membrane (PCL3%-E) exhibited randomly configured nanoscale fibres that were successfully customised to introduce pores of increased diameter, without compromising tensile properties. Additional to the PL absorption and release capabilities needed for MSC attraction and growth, PCL3%-E also provided a favourable surface for the proliferation and alignment of periosteum- and bone marrow derived-MSCs, whilst possessing a barrier function to cell migration. These results demonstrate the development of a promising biodegradable barrier membrane enabling PL release and MSC colonisation, two key functionalities needed for the in situ formation of a transitional periosteum-like structure, enabling movement towards single-surgery CSBD reconstruction.

Highlights

Critical size bone defects (CSBD) and fracture non-union pose a problem for patients, orthopaedic surgeons, and healthcare services worldwide
We developed a biodegradable induced periosteum-like membrane via free surface electrospinning (FSE) and tested its future clinical functionalities, i.e., as a carrier of platelet lysate (PL), multipotential stromal cells (MSC) homing, and preventing cellular infiltration
In an effort to improve the surgical repair of CSBD and reduce the number of surgeries needed per patient, the development of a membrane that replaces the role of periosteum and induced membrane’ (IM) is needed

Summary

Introduction

Critical size bone defects (CSBD) and fracture non-union pose a problem for patients, orthopaedic surgeons, and healthcare services worldwide. CSBDs are classified as greater than 1–2 cm in length or >50% of the bone circumference [1] and form through bone loss following trauma, tumour resection, infection, or established non-union [2]. A classic clinical approach to surgical repair includes bone debridement from the defect site, creating an aseptic vascular environment to be filled with autograft material, typically from the iliac crest. In the case of known or suspected infection, the two-step Masquelet technique is often carried out, following debridement the defect is filled with antibiotic-loaded bone cement (polymethyl methacrylate (PMMA)). Whilst the Masquelet technique has a union rate of over 80% [13,14], IM formation relies on the presence of PMMA and requires two separate surgeries, which can be costly and inconvenient for the patient

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