Degradable polymer bone adhesives

Abstract

Highly comminuted fractures and bone defects pose a significant challenge for orthopedic surgery. Current surgical procedures commonly rely on metal implants (such as bone plates, nails and pins) for fracture internal and external fixations, but they are likely to result in problems, such as stress shielding and poor bone healing. Bone adhesive represents an attractive alternative for the treatment of fracture. The ideal bone adhesive should satisfy several performance requirements, including high adhesion strength for bone tissues, rapid in-situ curing in a physiological environment, good biocompatibility with no toxicity, degradability, and good stability in vivo. Among these requirements, degradability is a crucial characteristic of bone adhesives. This property enables the material to be easily removed without the need for surgery at a later stage, ensuring the regeneration of bone tissue without any hindrance. The degradation rate of bone adhesive varies depending on the application scenarios and tissues, ranging from weeks to years. Many bone adhesives are unable to guarantee degradability while achieving other necessary performances. Therefore, this article provides a detailed overview of the strategies to fabricate biodegradable polymer bone adhesives that can maintain high bulk and adhesion strength, biocompatibility and other properties. Finally, the current challenges in the clinical translation of bone adhesives and their future development directions are discussed.

Keywords: Biodegradable materials; Bone adhesive; Bone fracture; Bone repair; Strong adhesion.

Fig. 1

Nature-derived Organic-inorganic strong bone adhesives. (a) The components and interactions of SF@TA@HA: the nucleophilic-phenol interaction and calcium-phenol coordination of TA with SF and HA respectively endow it with high toughness and adhesion strength . (b) Demonstration of the inorganic-organic strengthening of the adhesive via MBGN and GelDex, and bone glue as an all-in-one tool to flexibly adhere comminuted fragments . (c) Multifunctional bone adhesive with anti-infection and osteogenic activity by doping porous nanobioactive glass loaded with vancomycin in modified gelatin and oxidized starch . (d) Percentages of bone contact, bone area, and implant area over the 8–52 week period .

Fig. 2

Bone adhesives based on PU. (a) Schematic representation of the adhesion mechanism of a two-component PU adhesive composed of positively charged A and negatively charged B nanodispersions . (b) Histological analysis of transverse bone sections of PUA at 4, 12 and 24 weeks. NB: new bone, P: polymer, HB: host bone . (c) The structures and synthetic routes of DACO and PU-DACO .

Fig. 3

Bone adhesives based on PEG. (a) Schematic diagram of a hydrogel adhesive: The dissipative matrix consists of covalently cross-linked PEGDMA and ionic cross-linked natural alginate reinforced by cellulose fibers (NFC) . (b) Structure composition and adhesion mechanism of CS-PEG .

Fig. 4

Catechol-functionalized PEG adhesives. (a) Synthesis of iC-EPE prepolymer, and magnesium oxide (MgO) serves both as a crosslinker and composite filler to form injectable citrate-based mussel-inspired bioadhesives . (b) Structure of dopamine-functionalized four-arm PEG nanocomposite adhesives: curing, interfacial interactions and reversible physical crosslinking .

Fig. 5

Strategies for improving adhesion and mechanical properties of polyester adhesives. (a) Hyperbranched polyester was cured by photoinitiation of the thiol-ene click reaction to create a highly crosslinked tissue adhesive . (b) Nanobioactive glass-reinforced propylene fumarate (PPF) bone adhesives . (c) NHS-modified PLGA biodegradable nanoparticles with dopamine-modified alginate to enhance tissue adhesion through three interactions between tissues and nanocomposite adhesive . (d) Schematic illustration of flexible gelatin coated PCL nanopatch .

Fig. 6

Degradable crosslinkers: (a) Hydrolyzed poly(ethylene glycol) diacrylate (PEGDA) and oxidized alginate methacrylate (OxAlgMA) ,. (b) Enzyme-degraded gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) ,. (c) Disulfide bonds- containing bis(2-methacryloxyethyl) disulfide (MAD) and N,N’-bis (acryloyl) cystamine (BACA) ,.

Fig. 7

Strategies to improve the mechanical properties and stability of degradable crosslinker-crosslinked bone adhesives. The stress-stretch curve (a), maximum stress (b) and adhesion energy (c) of hydrogel adhesives with different crosslinkers, with N,N′-methylene bis(acrylamide) (MBAA, nondegradable crosslinker) as the control group . (d) The crosslinking and adhesion mechanism of the hydrogel adhesive AG-PEG . (e) The p(APMA-co-THMA) crosslinked with dextran-CHO to form a biodegradable adhesive hydrogel with high a density of hydrogen bonds by introducing “triple hydrogen bonding clusters (THBC)” .

Fig. 8

Strategies for introducing degradable units into the polymer backbone. (a) Preparation process of biodegradable adhesives based on UV light-initiated cross-linking of lactic acid and polycaprolactone oligomers . (b) Degradable mussel-like adhesive prepared by copolymerizing glycerol and methacrylic anhydride-modified PCL units with 3,4-dihydroxyphenyl-l-alanine acrylamide (L-DMA) molecular chains via UV polymerization . (c) Degradable hyperbranched tissue adhesive process prepared by introducing polyethylene glycol esters into the polymer backbone. Yellow: poly(trimethylene carbonate), blue: PEG, black: citric acid, green: hexamethylene diisocyanate . (d) Synthesis of poly (MDO-co-GMA-co-OEGMA) via rROP and its catechol-functionalized reaction process .