The Use of Fibers in Bone Tissue Engineering.

Bone tissue engineering aims to restore and maintain the function of bone by means of biomaterial-based scaffolds. This review specifically focuses on the use of fibers in biomaterials used for bone tissue engineering as suitable environment for bone tissue repair and regeneration. We present a bioinspired rationale behind the use of fibers in bone tissue engineering and provide an overview of the most common fiber fabrication methods, including solution, melt, and microfluidic spinning. Subsequently, we provide a brief overview of the composition of fibers that are used in bone tissue engineering, including fibers composed of (i) natural polymers (e.g., cellulose, collagen, gelatin, alginate, chitosan, and silk, (ii) synthetic polymers (e.g., polylactic acid [PLA], polycaprolactone, polyglycolic acid [PGA], polyethylene glycol, and polymer blends of PLA and PGA), (iii) ceramic fibers (e.g., aluminium oxide, titanium oxide, and zinc oxide), (iv) metallic fibers (e.g., titanium and its alloys, copper and magnesium), and (v) composite fibers. In addition, we review the most relevant fiber modification strategies that are used to enhance the (bio)functionality of these fibers. Finally, we provide an overview of the applicability of fibers in biomaterials for bone tissue engineering, with a specific focus on mechanical, pharmaceutical, and biological properties of fiber-functionalized biomaterials for bone tissue engineering. Impact statement Natural bone is a complex composite material composed of an extracellular matrix of mineralized fibers containing living cells and bioactive molecules. Consequently, the use of fibers in biomaterial-based scaffolds offers a wide variety of opportunities to replicate the functional performance of bone. This review provides an overview of the use of fibers in biomaterials for bone tissue engineering, thereby contributing to the design of novel fiber-functionalized bone-substituting biomaterials of improved functionality regarding their mechanical, pharmaceutical, and biological properties.

Micro- and macromechanical characterization of the influence of surface-modification of poly(vinyl alcohol) fibers on the reinforcement of calcium phosphate cements.

Calcium phosphate cements (CPCs) are frequently used as synthetic bone substitute materials due to their favorable osteocompatibility and handling properties. However, CPCs alone are inherently brittle and exhibit low strength and toughness, which restricts their clinical applicability to non-load bearing sites. Mechanical reinforcement of CPCs using fibers has proven to be an effective strategy to toughen these cements by transferring stress from the matrix to the fibers through frictional sliding at the interface. Therefore, tailoring the fiber-matrix affinity is paramount in designing highly toughened CPCs. However, the mechanistic correlation between this interaction and the macromechanical properties of fiber-reinforced CPCs has hardly been investigated to date. The aim of this study was to tailor the fiber-matrix interface affinity by modifying the surface of poly(vinyl alcohol) (PVA) fibers and correlate their interfacial properties to macromechanical properties (i.e. fracture toughness, work-of-fracture and tensile strength) of CPCs. Results from single fiber pullout tests reveal that the surface modification of PVA fibers increased their hydrophilicity and improved their affinity to the CPC matrix. This observation was evidenced by an increase in the interfacial shear strength and a reduction in the critical fiber embedment length (i.e. maximum embedded length from which a fiber can be pulled out without rupture). This increased interface affinity facilitated energy dissipation during fracture of CPCs subjected to macromechanical three-point flexure and tensile tests. The fracture toughness also significantly improved, even for CPCs reinforced with fibers of lengths greater than their critical fiber embedment length, suggesting that other crack-arresting mechanisms also play an important role in mechanically reinforcing CPCs. Overall, these basic insights will improve the understanding of the correlation between micro- and macromechanical characteristics of fiber-reinforced CPCs.

Thermoresponsive Brushes Facilitate Effective Reinforcement of Calcium Phosphate Cements.

Calcium phosphate ceramics are frequently applied to stimulate regeneration of bone in view of their excellent biological compatibility with bone tissue. Unfortunately, these bioceramics are also highly brittle. To improve their toughness, fibers can be incorporated as the reinforcing component for the calcium phosphate cements. Herein, we functionalize the surface of poly(vinyl alcohol) fibers with thermoresponsive poly(N-isopropylacrylamide) brushes of tunable thickness to improve simultaneously fiber dispersion and fiber-matrix affinity. These brushes shift from hydrophilic to hydrophobic behavior at temperatures above their lower critical solution temperature of 32 °C. This dual thermoresponsive shift favors fiber dispersion throughout the hydrophilic calcium phosphate cements (at 21 °C) and toughens these cements when reaching their hydrophobic state (at 37 °C). The reinforcement efficacy of these surface-modified fibers was almost double at 37 versus 21 °C, which confirms the strong potential of thermoresponsive fibers for reinforcement of calcium phosphate cements.

Surface functionalization of polylactic acid fibers with alendronate groups does not improve the mechanical properties of fiber-reinforced calcium phosphate cements.

Calcium phosphate cements (CPCs) are frequently used as synthetic bone substitute, but their intrinsic low fracture toughness impedes their application in highly loaded skeletal sites. However, fibers can be used to reduce the brittleness of these CPCs provided that the affinity between the fibers and cement matrix facilitates the transfer of loads from the matrix to the fibers. The aim of the present work was to improve the interface between hydrophobic polylactic acid (PLA) microfibers and hydrophilic CPC. To this end, calcium-binding alendronate groups were conjugated onto the surface of PLA microfibers via different strategies to immobilize a tunable amount of alendronate onto the fiber surface. CPCs reinforced with PLA fibers revealed toughness values which were up to 50-fold higher than unreinforced CPCs. Nevertheless, surface functionalization of PLA microfibers with alendronate groups did not improve the mechanical properties of fiber-reinforced CPCs.

Fiber-reinforced colloidal gels as injectable and moldable biomaterials for regenerative medicine.

Hydrogels are the preferred material choice for various strategies in regenerative medicine. Nevertheless, due to their high water content and soft nature, these materials are often mechanically weak, which limits their applicability. This study demonstrates mechanical reinforcement of colloidal gels at microscale using discrete polyester fibers, as confirmed by rheological, compression and nanoindentation tests. This reinforcement strategy results in injectable and moldable colloidal gels with improved mechanical performance. The fully organic gels presented here are cytocompatible and can maintain their mechanical integrity under physiological conditions. Consequently, these gels exhibit a strong potential for applications in tissue engineering and regenerative medicine.

Polyester fibers can be rendered calcium phosphate-binding by surface functionalization with bisphosphonate groups.

Fibers are often used as structural elements to improve the mechanical properties of materials such as brittle ceramic matrices by facilitating the dissipation of energy. However, this energy dissipation is mainly controlled by the interface between the two components, and a poorly designed fiber-matrix interface strongly reduces the efficacy of fiber reinforcement. Here, we present a versatile approach to control the affinity of biocompatible fibers to calcium-containing matrices to maximize the efficacy of reinforcement of calcium phosphates-based bioceramics by means of polymeric fibers. To this end, polyester fibers of tunable length were produced by electrospinning and aminolysis, followed by covalent attachment of alendronate, a bisphosphonate molecule with strong calcium-binding affinity, to the surface of the fibers. The proposed method allowed for selective control over the amount of alendronate conjugation, thereby improving the affinity of polyester fibers toward calcium phosphate bioceramics. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2335-2342, 2017.