Tuning of Silver Content on the Antibacterial and Biological Properties of Poly(ɛ-caprolactone)/Biphasic Calcium Phosphate 3D-Scaffolds for Bone Tissue Engineering

Abstract

There is a growing interest in tissue engineering, in which biomaterials play a pivotal role in promoting bone regeneration. Furthermore, smart functionalization can provide biomaterials with the additional role of preventing orthopedic infections. Due to the growing microbial resistance to antimicrobials used to treat those infections, metal ions, such as silver, thanks to their known wide range of bactericidal properties, are believed to be promising additives in developing antibacterial biomaterials. In this work, novel poly(ε-caprolactone) (PCL)-based 3D scaffolds have been designed and developed, where the polymer matrix was modified with both silver (Ag), to supply antibacterial behavior, and calcium phosphates (biphasic calcium phosphate, BCP) particles to impart bioactive/bioresorbable properties. The microstructural analysis showed that constructs were characterized by square-shaped macropores, in line with the morphology and size of the templating salts used as pore formers. Degradation tests demonstrated the important role of calcium phosphates in improving PCL hydrophilicity, leading to a higher degradation degree for BCP/PCL composites compared to the neat polymer after 18 days of soaking. The appearance of an inhibition halo around the silver-functionalized PCL scaffolds for assayed microorganisms and a significant (p < 0.05) decrease in both adherent and planktonic bacteria demonstrate the Ag+ release from the 3D constructs. Furthermore, the PCL scaffolds enriched with the lowest silver percentages did not hamper the viability and proliferation of Saos-2 cells. A synergic combination of antimicrobial, osteoproliferative and biodegradable features provided to 3D scaffolds the required potential for bone tissue engineering, beside anti-microbial properties for reduction in prosthetic joints infections.

Is Silver Addition to Scaffolds Based on Polycaprolactone Blended with Calcium Phosphates Able to Inhibit Candida albicans and Candida auris Adhesion and Biofilm Formation?

“…Conversely, besides the 3D structure, the scaffolds developed here are characterized by hierarchal porosity, where the micro- and macro-porosity have a synergic effect on osteointegration and osteogenesis, as required in bone tissue engineering [ 28 , 29 , 30 ]. In our previous research, we demonstrated that PCL and BCP/PCL can be added along with different antimicrobials—both silver and essential oils—without affecting their higher interconnected porosity [ 6 , 10 , 11 ]. Similarly, in research by Sadiasa and colleagues in 2014, the structure of a 3D scaffold based on poly(L-lactic acid) (PLLA) and PCL was evaluated; increased porosity and pore size were observed, particularly when PLLA was added [ 31 ].…”

“…In a previous study, we revealed that silver introduced at 1.67% into PCL-based 3D scaffolds significantly affects Saos-2 cell viability [ 10 ]; thus, we reduced its concentration to ~1%. Subsequently, when the silver content was decreased, the Saos-2 cells were viable and, additionally, proliferated into the constructs [ 6 ]. For these reasons, the following experiments were performed on PCL-based specimens with the lowest silver concentrations, which were 0.79% and 1% for the 3D scaffolds pored with NaNO 3 and NaCl, respectively.…”

“…In particular, PCL is a highly biocompatible and bioresorbable polymer that, upon its implantation, is not necessary to remove at the end of its function [ 4 , 5 ]. PCL is also a suitable biomaterial for producing three-dimensional (3D) constructs, called scaffolds, which are an advanced therapeutic solution for cavity-filling in bone disease or for the healing of fractured bone [ 6 , 7 , 8 ]. PCL-based devices might be produced using various methods: the salt-leaching method permits the preparation of highly porous scaffolds that can be used for long-term implants and in targeted drug release applications [ 5 ].…”

“…In our previous work, we established that PCL, either pure or blended with BCP, is a suitable matrix for creating 3D scaffolds able to promote osteoblast adhesion and proliferation without displaying cytotoxic behavior. Additionally, PCL could be used with silver to counteract both Gram-positive and Gram-negative bacterial growth/adhesion and biofilm formation [ 6 , 9 , 10 , 11 ]. However, until now, no data regarding its anti- Candida activities if incorporated in 3D PCL-based scaffolds re available in the scientific literature.…”

Use of Biomaterials in 3D Printing as a Solution to Microbial Infections in Arthroplasty and Osseous Reconstruction

“…An experimental BCP formulation has been proven capable of reliably eluting antibiotics [ 152 ]; combinations with silver ions [ 153 , 154 ] or chitosan [ 143 , 155 ] have also demonstrated antimicrobial properties. In the research of Chen et al [ 143 ], even though no testing was performed on bacterial cells, their compound promoted osteoblast differentiation and activity; this can have important implications given the interplay between osteoblasts and bacterial infections [ 156 , 157 , 158 , 159 ] ( Table 3 ).…”