New Generation of Osteoinductive and Antimicrobial Polycaprolactone-Based Scaffolds in Bone Tissue Engineering: A Review

Abstract

With respect to other fields, bone tissue engineering has significantly expanded in recent years, leading not only to relevant advances in biomedical applications but also to innovative perspectives. Polycaprolactone (PCL), produced in the beginning of the 1930s, is a biocompatible and biodegradable polymer. Due to its mechanical and physicochemical features, as well as being easily shapeable, PCL-based constructs can be produced with different shapes and degradation kinetics. Moreover, due to various development processes, PCL can be made as 3D scaffolds or fibres for bone tissue regeneration applications. This outstanding biopolymer is versatile because it can be modified by adding agents with antimicrobial properties, not only antibiotics/antifungals, but also metal ions or natural compounds. In addition, to ameliorate its osteoproliferative features, it can be blended with calcium phosphates. This review is an overview of the current state of our recent investigation into PCL modifications designed to impair microbial adhesive capability and, in parallel, to allow eukaryotic cell viability and integration, in comparison with previous reviews and excellent research papers. Our recent results demonstrated that the developed 3D constructs had a high interconnected porosity, and the addition of biphasic calcium phosphate improved human cell attachment and proliferation. The incorporation of alternative antimicrobials-for instance, silver and essential oils-at tuneable concentrations counteracted microbial growth and biofilm formation, without affecting eukaryotic cells' viability. Notably, this challenging research area needs the multidisciplinary work of material scientists, biologists, and orthopaedic surgeons to determine the most suitable modifications on biomaterials to design favourable 3D scaffolds based on PCL for the targeted healing of damaged bone tissue.

Keywords: antimicrobial agents; bacterial adhesion; biofilm formation; calcium phosphates; essential oils; eukaryotic cell proliferation and integration; metal ions; polycaprolactone; scaffolds.

Figure 3

Representative micrographs of PCL-based scaffolds fabricated by ES/MES (a–c), SC/PL (d–f), and TIPS (g–i). Electrospun PCL (a), PCL with 1.0% HA (b) scaffolds (reprinted from [17] under the CCC license n. 5766001110392), and (c) Cu-doped wollastonite/PCL scaffolds after immersion in simulated body fluid for 14 days (reprinted from [30] under the CCC license n. 5766071417184). Lower (d) and higher (e) magnification images of PCL scaffolds and PCL/biphasic calcium phosphate scaffolds obtained by the SC/PL method, using NaCl as a template; (f) a biphasic calcium phosphate (BCP)/PCL sample showing the fine and homogeneous distribution of the calcium phosphate particles inside the polymer matrix (reprinted from [42] under an open access Creative Common CC BY license). TIPS-derived scaffolds containing PCL and virgin olive oil (g) (modified from [52] under the CCC license n. 5766100665534) and PLA/PCL/gelatin nanofibers (h) also added with 0.1% taurine (i) (reprinted from [53] under an open access Creative Common CC BY license).

Figure 1

Key features of pure PCL for bone tissue engineering.

Figure 2

A representative image illustrating the enhanced properties of PCL when blended with calcium phosphates and functionalised with antimicrobial agents.

Figure 4

Representative micrographs of PCL-based scaffolds fabricated by 3D printing techniques: FDM (a,b), SLS (c–e), and SLA/DLP (f–h). (a) PCL/β-TCP (left) and PCL/β-TCP/nano-MgO (right) 3D-printed scaffolds, and (b) details of pore and strut size (modified by [74] under the CCC license n. 5766120164887); (c) PCL/HA (70:30) composite lattice scaffolds fabricated by SLS and (d) strut sizes measured in the different directions (modified by [90] under the CCC license n. 5766120654002); (e) irregular shape of a PCL/HA scaffold (modified by [91] under the open access Creative Common CC BY license); (f) a digital photo of a PCL scaffold fabricated by SLA and its related microstructure at lower (g) and higher (h) magnification (modified by [96] under the CCC license n. 5766540484597 and 5766550004916).

Figure 5

The relevant features of PCL-based 3D scaffolds blended with calcium phosphates designed for bone tissue engineering.

Figure 6

Results of the cytocompatibility experiments of the PCL-based scaffolds when posed in contact with eukaryotic cells.