Abstract
Using phantom samples, we investigated the feasibility of spatially-offset Raman spectroscopy (SORS) as a tool for monitoring non-invasively the mineralization of bone tissue engineering scaffold in-vivo. The phantom samples consisted of 3D-printed scaffolds of poly-caprolactone (PCL) and hydroxyapatite (HA) blends, with varying concentrations of HA, to mimic the mineralisation process. The scaffolds were covered by a 4 mm layer of skin to simulate the real in-vivo measurement conditions. At a concentration of HA approximately 1/3 that of bone (~0.6 g/cm3), the characteristic Raman band of HA (960 cm−1) was detectable when the PCL:HA layer was located at 4 mm depth within the scaffold (i.e. 8 mm below the skin surface). For the layers of the PCL:HA immediately under the skin (i.e. top of the scaffold), the detection limit of HA was 0.18 g/cm3, which is approximately one order of magnitude lower than that of bone. Similar results were also found for the phantoms simulating uniform and inward gradual mineralisation of the scaffold, indicating the suitability of SORS to detect early stages of mineralisation. Nevertheless, the results also show that the contribution of the materials surrounding the scaffold can be significant and methods for subtraction need to be investigated in the future. In conclusion, these results indicate that spatially-offset Raman spectroscopy is a promising technique for in-vivo longitudinal monitoring scaffold mineralization and bone re-growth.
Highlights
A common treatment for major bone damage is autologous bone grafting [1]
For each ratio of the PCL:HA blend, the PCL:HA layer was placed in turn at 0, 2, 4, 6, and 8 mm beneath the skin layer
Using phantom samples based on 3D-printed PCL:HA scaffolds we investigated the feasibility of spatially-offset Raman spectroscopy (SORS) to monitor mineralisation of bone tissue engineering scaffolds in large animal models
Summary
A common treatment for major bone damage is autologous bone grafting [1]. Autologous grafting is not the optimal solution because the quality and quantity of bone grafts that can be harvested is sometimes not sufficient to meet demand, it increases the risk of infection, and can lead to haemorrhaging, cosmetic disability, nerve damage, and a loss of function. An alternative to autologous grafts is the use of tissue engineered scaffolds that can be implanted in the defect to offer a 3D structure to support and stimulate the regeneration and repair of the bone [2]. In vivo models where scaffolds are implanted in critical bone defects in large animals (e.g. sheep) have been commonly used to model the healing process in humans [3]. These studies provide a better understanding of the bone repair process in order to optimise the physical and chemical properties of the material to reduce healing time and improve the quality of the newly formed bone. What will constitute a critical defect depends on the size of the bone damaged [5,6], and the age and health of the patient [7,8]
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