GB2577881A

GB2577881A - Porous bioceramic scaffolds and preparation method thereof

Info

Publication number: GB2577881A
Application number: GB1816371.7A
Authority: GB
Inventors: Kamboj Nikhil; Aghayan Marina
Original assignee: Functional Advanced Composite Tech Industries Ltd
Current assignee: Functional Advanced Composite Tech Industries Ltd
Priority date: 2018-10-08
Filing date: 2018-10-08
Publication date: 2020-04-15
Also published as: GB201816371D0

Abstract

The present invention relates to porous bioactive and biodegradable scaffolds for use in reconstructive bone surgeries. The scaffolds are prepared by a one-step powder bed additive manufacturing (AM) technology, particularly, selective laser sintering (SLS), using a special feedstock. The feedstock is a composite powder comprising of at least one ceramic or non‑metallic inorganic component (20-80 wt.%) and at least one metallic or metalloid component (20-80 wt%). The metallic or metalloid component is selected from silicon, titanium (and alloys thereof), aluminium (and alloys thereof) and stainless steel. The non-metallic or ceramic component is selected from tricalciumphosphate (TCP), dicalciumphosphate (DCP), monocalciumphosphate (MCP), tetracalciumphosphate, hydroxylapatite, calcium oxide, silica, titanium dioxide, aluminium oxide(s), wollastonite, calcium silicate and P2O5-SiO2 based glasses. The feedstock is prepared by ball milling using ceramic balls. The geometry, porosity and bioactivity and biodegradability of the scaffolds can be controlled changing the composition of the feedstock and the parameters of selective laser sintering.

Description

Porous bioceramic scaffolds and preparation method thereof Nikhil Kamboji, Marina Aghayani IFunctional Advanced Composite Technology Industries, Oismae tee 124-12, Tallinn 13513, Estonia

Technical Field

The present invention relates to bioactive scaffolds for bone regeneration that can be fabricated by selective laser sintering. Additionally, the present invention relates to the feedstock for selective laser sintering, and process of preparation of the scaffolds that employ selective laser melting technology and the as-prepared feedstock. The scaffolds can be partially of completely biodegradable. The scaffolds comprise at least one ceramic of non-metallic inorganic component and one metallic or metalloid component.

Technical Background

Bone is one of the most transplanted tissue [I]. Traditionally the autologous and allogeneic clinical treatments have been used to repair or replace the diseased, infection or lost bone as a result of trauma. However, these treatments have a list of drawbacks, such as risk of infection, donor-site morbidity, immune rejection, etc. Therefore, the bone tissue engineering is focused to provide alternative methods synthesize and manufacture bone. An option is developing scaffolds, which are three dimensional biocompatible structures which can mimic the bone tissue properties and provide bone tissue formation. The chemical composition, mechanical properties, pore size, volume, interconnectivity are critical parameters that strongly influence on the performance of the scaffolds [2]. For instance, the pore size should be over 300 um to enhance the bone formation. Open and interconnected pores are necessary for better bone regeneration and blood circulation, nutrition and bone healing. For optimum bone healing, the full geometric congruence between the implant and adjacent tissues is of high importance.

However, fabrication of osteoconductive implants with complex shape and designed porosity is a challenge.

The additive manufacturing (AM) technology enables fabrication of implants with controlled microstructure, shape, mechanical properties [3-5]. Two basic categories of AM technology exist which are applied to produce ceramic based implants: direct and indirect. In the case of direct AM, the powder is sintered by localized high power laser or electron beam. Direct AM technology was successfully applied for metals and metal alloys. The desired properties very often were achieved without further post heat-treatment. However, manufacturing of ceramic based scaffolds by direct AM, particularly selective laser sintering usually end up with failure. In many cases, the obtained parts possess residual stresses and high roughness. This is caused by the low absorption of laser beam energy, the poor thermal shock resistance and high melting point of ceramics.

Commercially available scaffolds or complex shaped ceramic parts are made of indirect AM, which is a multi-step technology. This technology includes post-fabrication heat treatment for thermal debinding and sintering of the printed object. Debinding and sintering can result in degradation of physical-chemical characteristics of the substrate and changes of initially designed structure [6-11].

Bioceramics such as calcium phosphate, calcium silicate, hydroxyapatite, Bioglass and their combination are widely used in bone tissue engineering due to their excellent biocompatibility and osteroconductivity [II]. Therefore, fast, reliable and easy manufacturing of bioceramic based scaffolds are of high importance. Fabrication of bioceramic implants by direct additive manufacturing technology allows to escape from the challenges such as long duration of the process, post-fabrication heat treatments with its negative consequences described above.

In addition, the biodegradable and bioactive custom-made scaffolds, which are possible to fabricate by additive manufacturing technology has high potential to open a new era in regenerative medicine. Usually the natural bone grows slower on scaffolds fabricated by additive manufacturing. This is caused by the high temperature feature of this or post-processing process which passivates the bioactive components decreasing their surface area and resulting in physician and chemical changes. This results in a long duration of the healing time. In addition, in order to decrease the healing time, and escape from unfavorable side-effects, it is important to control precisely the pore size, pore interconnectiyity, pore distribution and geometry. These parameters are responsible for the blood circulation, nutrition, healing of the bone, mechanical properties and bioactivity of the scaffolds.

However, the existing methods are not able yet to control those parameters with high accuracy.

Disclosure of Invention

The objective of the present invention is to manufacture bioactive scaffolds for bone regeneration with controlled structure by selective laser sintering. Another objective of the invention is to use a specially designed feedstock for manufacture of the bioactive scaffold for bone regeneration. The feedstock comprises of at least one ceramic or non-metallic inorganic component, and at least one metallic or metalloid component.

The uniqueness of the method includes possibility to fabricate scaffolds with controlled stnicture and mechanical properties in one step. The post-fabrication heat treatment is not a compulsory manufacturing step, which will dramatically decrease the manufacturing overall duration and cost.

Thus, the invention describes bioactive and biodegradable scaffolds and the methods of manufacturing thereof comprising: (a) Preparation of feedstock for bioactive scaffold for bone regeneration: The feedstock is prepared mixing the raw materials comprising ceramic material and/or non-metallic inorganic and metallic and/or metalloid material by wet or dry ball milling using ceramic balls. Afterwards, dring of the milled powder from 1 hours to 48 hours in an oven heated from 40-220 °C is required. After the drying the powder are sieved to provide high flowability; (b) Manufacturing: The as-prepared feedstock is applied for manufacturing. In this current study the inventors used selective laser sintering technology. Before running the SLS process, the scaffolds should be carefully designed and modeled, taking into account the bio-mechanical functionality scaffold and requirements towards it.

It should be noted that this technology allows to obtain at least 3D printed scaffolds with interconnected porosity with the pore size from 10 nm to 5000pm. The scaffold as the bone implant manufactured from feedstock according to present invention is bioactive and partially or completely biodegradable

Brief description of the drawings

The present invention will be described in detail in the following embodiments with references to the drawings where.

Fig 1 illustrates the scanning electron microscopy (SEM) pictures of the feedstock for scaffold 25 with composition of 50 wt. % (by weight) CaSiO3 and 50 wt.% (by weight) Si.

Fig 2 illustrates the scanning electron microscopy (SEND pictures of the manufactured scaffolds with the pores size of 400 pm and <50 pm in diameter and composition of 50 wt % CaSiO3 and 50 wt.% Si.

Fig 3 illustrates the scanning electron microscopy (SEM) pictures of hydroxyapatite grown on 30 the scaffolds with composition of 50 wt.% CaSiO3 and 50 wt.% Si. immersed in the SBF solution for (a) 3; (b) 7; (c) 14; (d) 21 days.

Fig 4 Raman spectrum of the scaffolds with composition of 50 wt CaS103 and 50 wt.% Si. immersed in the SBF solution for 3 days Fig 5 The weight change of the scaffold with composition of 50 wt.% CaSiO3 and 50 wt.% Si in Tris-HC1 and SBF in various time periods (3, 7 and 14 days).

Fig 6 CaO (black) and 5i02 (grey) concentrations in Tris buffer as a function of days.

Detailed description of the embodiments

The present invention discloses a bioactive and biodegradable (partially or completely) material for porous bioceramic scaffold and a method for direct additive manufacturing thereof.

In order to manufacture bioactive and biodegradable porous scaffold as bone implant, a feedstock comprising at least one ceramic material and/or non-metallic inorganic material and at least one metallic and/or metalloid material is used, where the metallic or metalloid material is selected from the group consisting of silicon and its alloys, titanium and its alloys, aluminum and its alloys, stainless steel and its alloys, and their mixtures thereof The ceramic or non-metallic inorganic materials is selected from the group consisting of TCP (tricaiciumphosphate), MCP (monocalciumphosphate), DCP (dicalciumphosphate), tetracalciumphosphate, hydroxylapatite, calcium oxide, silica, titanium oxide, aluminium oxide, wollastonite, calcium silicate, P205-Si02 based glasses, and mixtures thereof By using said mixture as a feedstock thereafter the scaffold is fabricated by SLS (Selective Laser Sintering). SLS is an AM technique that uses a laser as the power source to sinter powdered material. This technology is usually applied to prepare metal or metal alloy based parts with complex geometries and good dimensional tolerance. The starting point is a 3D Computer-Aided Design (CAD) model of the scaffold (bone) that is created on a computer. The model of the scaffold as bone implant is virtually sliced into thin layers with a typical layer thickness of 20 pm -1 mm. The model virtually sliced into layers is processed in 3D printer.

With 3D printer the composite powder layer as 2D slice corresponding to virtual slice is distributed, then the 2D slice is heated by a powerful laser beam sintering the targeted location of the layer. The sintering process is repeated layer by layer, slice by slice, until the complete shape formation of the scaffold (bone implant). Then the scaffold is removed from the powder bed and post processed according to requirements.

Particularly, the manufacturing of the above-mentioned scaffolds is carried out SLS technology using the laser exposure time of 50-360 ms and laser current of 600-1400 mA.

Removing already manufactured scaffold from the powder bed of the SLS device, a post-fabrication heat treatment can be applied. This stage is not compulsory, but it is not excluded. The post-fabrication heat treatment comprises sintering, hardening, coating, infiltrating of the scaffolds. For example, heat treatment of the CaO/Si scaffold at 900 °C drastically improves the compressive strength of the scaffold. As well as, the scaffolds can be coated by various therapeutic coatings. Therapeutic or drug delivery coatings are not new technology. This technology enables to control the drug delivery in the body for the designed period of time and achieve its desired therapeutic effect with minimum side effects [12-14]. Designing and selecting appropriate material for coating it is possible to control the drug delivery time. For example, in oncologic reconstructive surgery, an effective method can be replacing the bone with scaffolds coated with antineoplastic drug containing materials, controlling its local therapeutic effect and delivery time [15]. This technology is applied for greater level of healthcare and improved patient outcomes.

For evaluation of in vitro bioactivity and biodegradability, the printed samples were placed in polyethylene vials with simulated body fluid (SBF) solution and maintained in a water bath at 37 °C. A sample weight/volume of solution with ratio of 0.002 g/cm3 was used in each experiment. Incubation periods of 7 and 14 days were used. During the incubation period, the SBF solution was replaced by freshly prepared SBF solution at 24 h intervals. This procedure was used to avoid microorganism proliferation and also to keep the pH close to 7.3. After respective immersion times, the samples were rinsed in deionized water and dries a room temperature for bioactivity test. For bioactivity test, the samples were covered with silver and analyzed by SEN4 coupled to energy dispersive spectroscopy. The formation of the hydroxyapatite (HA) layer was monitored through Raman spectroscopy using the 514.5 nm laser line. Raman spectra were collected over the range of 1500-200 cm-1. Microstructure analyses were also used to follow growth of the HA layer.

To investigate the ion release from the scaffolds and their weight loss, the scaffolds were soaked in a Tris-HC1 solution for 1, 7 and 14 days (solution volume to scaffold mass: 1L/g), dried at 120 °C, and weighed via an analytical balance. The concentrations of CaO and SiOz were measured by inductively coupled plasma atomic emission spectrometry.

Compressive strength tests were performed on the cylindrical samples with 10 mm of diameter and 5 mm of height were loaded at a crosshead speed of 0.5 mm/min C) Feedstock The terms relate to the composite powder used in a 3D printing process, i.e the material being printed The feedstock is printable by selective laser sintering. The feedstock is comprising - 20-80 % by weight of the total composite powder (w/w) of at least one ceramic material or non-metallic inorganic compound - 20-80 % by weight of the total composite powder (w/w) of at least one metallic or metalloid component The present invention provides a method for fabricating bioimplants by SLS

Example 1

To achieve the above objective, the technical solution proposed by the present invention TiCaSiO3bioactive, biodegradable scaffold was prepared by the following method.

1 The 30 wt. % Ti64 alloy (Ti-6A1-4V) powder was mixed with 70 wt.% CaSiO3 powder and ball milled for 24 hours using zirconia balls.

2 SLS was performed using Metal 3D printer (ReaLizer GmbH SL1M-50, Germany). The main characteristics of the machine and the process parameters are specified in Table 3, TABLE 3: Characteristics of the SLS equipment and sinter'ng parameters.

Example Layer thickness, gm Laser current Point distance, !Lin Exposure time,

MS

1 25 1200 10 125 2 10 800 5 325 3 50 1400 25 250 3. Rec angular samples with pore size of 400 to 900)tm was designed for the bioscaffolds production. The designed scaffolds dimensions were 10x20x2.5mm. The scaffolds were applied for in vitro tests.

Example 2

To achieve the above objective, the technical solution proposed by the present invention Si-25 BioGlass (5i02-53wt.°4), CaO-20wt.%, Na20-6vvV1/0, P205-4wt.%, K20-12wt.%, Mg0-5wt.%) bioactive, biodegradable scaffold was prepared by the following method: 1. The 50 wt. °, O Si powder was mixed with 50 wt.% Bioglass powder and ball milled for 24 hours using zirconia balls.

2. SLS was performed using Metal 3D printer (ReaLizer GmbH SLM-50, Germany). The main characteristics of the machine and the process parameters are specified in Table 3.

3. Rectangular samples with pore size of 50nm to 200um was designed for the bioscaffolds production. The designed scaffolds dimensions were 10x20x2.5mm. The scaffolds were applied for in vitro tests.

Example 3

To achieve the above objective, the technical solution proposed by the present invention stainless steel-Ca3PO4 scaffold was prepared by the following method: I. The 80 wt. % stainless steel 304 powder was mixed with 20 wt.% Ca3PO4 powder and ball milled for 24 hours using zirconia balls.

2 Selective laser sintering (SLS) was performed using Metal 3D printer (ReaLizer GmbH SLM-50, Germany). The main characteristics of the machine and the process parameters are specified in Table 3.

Rectangular samples with pore size of 200um to 800nm containing submicron porosity was designed for the bioscaffolds production. The designed scaffolds dimensions were 10x20x2.5mm The scaffolds were applied for in vitro analyses.

Example 4

To achieve the above objective, the technical solution proposed by the present invention SiCaSiO3 bioactive scaffold was prepared by the following method: 1 IN order to prepare the feedstock (Fig. 1) the 50 wt. (1)) Si powder was mixed with 50 wt.% CaSiO3 powder and ball milled for 24 hours using zirconia balls.

2 SLS was performed using Metal 3D printer (ReaLizer GmbII SLM-50, Germany). The main characteristics of the machine and the process parameters are specified in Table 3, 3 Rectangular samples with pore size of 400um was designed for the bioscaffolds production (Fig. 2). The designed scaffolds dimensions were 10x20x2.5mm.

The scaffolds were applied for in vitro analyses. The results are illustrated in Fig 3-6.

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