3D printing of PLA/n-HA composite scaffolds with customized mechanical properties and biological functions for bone tissue engineering

Abstract

Bone defect caused by trauma, tumor, infection, and other reasons is a thorny problem that needs to be solved in orthopedic clinic. Customized bone repair biomaterials and their fabrication still need to be explored. Three-dimensional (3D) printing is a high-speed fabrication process for bone tissue biomaterials, which paves the way of solving clinical bone defect problems in a new way. In this study, the fused deposition modeling (FDM) technology was used to prepare the composite scaffolds of polylactic acid (PLA) and nano-hydroxyapatite (n-HA). The composite scaffold was optimized by material characterization, mechanical property test, and in vitro bone marrow mesenchymal stem cells biocompatibility test. Finally, a rabbit model was established to evaluate the osteogenic ability of PLA/n-HA scaffolds in vivo. The results showed that the PLA/n-HA composites proposed in this study were highly printable, and the printed scaffold showed tunable mechanical strength accompanied by the proportion of n-HA components. The biocompatibility and osteogenic induction properties were proved better than that of the pure PLA scaffold. This composite scaffold of PLA and n-HA provides a promising strategy for the repair of large bone defects.

Introduction

Bone is a kind of dynamic hard tissue, which is usually characterized by high hardness and moderate self-healing ability. However, trauma, resection of tumor, and infection often cause large bone defects. Once the size of the bone defect exceeds the critical value, self-healing would be impossible [1]. The treatment of critical bone defects often requires the implantation of bone substitutes. As the gold standard for bone defects, autologous bone grafts are often difficult to perform due to limited quantity, painful bone extraction, pain at the donor site, and potential infection. Allograft has a wide range of sources, but its biological activity is low, and it is easy to cause pathogen infection and immune rejection [2,3]. Therefore, researchers have explored many biomaterials as a suitable bone substitute [4]. Various materials such as metal, ceramic, and polymer scaffolds were served as bone substitutes. However, these scaffolds showed low osteogenic activity, poor histocompatibility, and slow degradation rate, making it difficult to achieve satisfactory results [5]. To solve these problems, novel bone tissue repair biomaterial, including its fabrication process, was developed for the treatment of critical bone defects regeneration [6,7].

In recent years, 3D printing breaks through the limitations of traditional material processing [8,9]. The specific 3D printing bio-ink can be developed by adjusting the ratio parameters of different materials, such as printing performance, mechanical performance and, biological activity [10,11]. Fused deposition modeling (FDM) allows printing various materials, including ceramics, polymers, and composites [12]^. Through FDM 3D printing technology, the internal porosity, pore size, and interconnected structure of biomaterials can be well controlled [13,14].

The scaffold requirements for critical bone defects need excellent bioactive properties and need good mechanical strength [4]. Poly-lactic acid (PLA) is a kind of potential clinical polymer that can be biodegraded, has similar compressive strength (2–39 MPa) to natural bone (2–12 MPa) [15]. Although the PLA has excellent mechanical properties, it shows the disadvantage of low biological activity [13,16]. The advantage of composite materials is that they can maintain the edges of each material and make up for each other's shortcomings [17,18]. Nano-hydroxyapatite (n-HA) usually be used as a coating material to increase the surface activity, due to the similar size of the apatite in natural bones [19]. In addition to increased biological activity, the combination of PLA and n-HA has additional benefits. PLA degradation will produce acidic degradation products that affect the acid-base balance of the defect site, and n-HA can be added to neutralize the acid [20,21].

In this study, PLA/n-HA composite scaffolds with 0%, 10%, 20%, 30%, 40% and, 50% n-HA gradients were fabricated for 3D printing of porous bone tissue scaffold. The characterization, mechanical properties, and in vitro biocompatibility of PLA/n-HA composite scaffolds were systematically studied and analyzed, and the best n-HA ratio was proposed to cure critical bone defect. The results show these optimized scaffolds simulate the organic combination of collagen and calcium in bone tissue, which mimics the natural bone matrix environment, and can to be used in critical bone defects repair.