Bioinspired Mineral–Organic Bioresorbable Bone Adhesive

Abstract

Bioresorbable bone adhesives have potential to revolutionize the clinical treatment of the human skeletal system, ranging from the fixation and osteointegration of permanent implants to the direct healing and fusion of bones without permanent fixation hardware. Despite an unmet need, there are currently no bone adhesives in clinical use that provide a strong enough bond to wet bone while possessing good osteointegration and bioresorbability. Inspired by the sandcastle worm that creates a protective tubular shell around its body using a proteinaceous adhesive, a novel bone adhesive is introduced, based on tetracalcium phosphate and phosphoserine, that cures in minutes in an aqueous environment and provides high bone-to-bone adhesive strength. The new material is measured to be 10 times more adhesive than bioresorbable calcium phosphate cement and 7.5 times more adhesive than non-resorbable poly(methyl methacrylate) bone cement, both of which are standard of care in the clinic today. The bone adhesive also demonstrates chemical adhesion to titanium approximately twice that of its adhesion to bone, unlocking the potential for adherence to metallic implants during surrounding bony incorporation. Finally, the bone adhesive is shown to demonstrate osteointegration and bioresorbability over a 52-week period in a critically sized distal femur defect in rabbits.

Bioinspired Mineral–Organic Bone Adhesives for Stable Fracture Fixation and Accelerated Bone Regeneration

“…Conventional technologies, including the use of metallic plates and screws, are safe and serviceable but often suffer from foreign‐body reactions, aseptic loosening, and the need to be surgically replaced or removed . Bone adhesives, such as poly(methyl methacrylate) (PMMA) and calcium phosphate (CPC) bone cements, are gaining special attention as alternative treatments that have the potential to revolutionize procedures towards more personalized bone repair . Despite their routine use, severe deficiencies remain in current products, including cytotoxicity concerns, inappropriate mechanical strength, poor fixation performance in biological environments, and consequently notoriously high failure rates for bone healing .…”

A biomechanical test model for evaluating osseous and osteochondral tissue adhesives

“…A number of adhesives have been proposed for fracture repair, including acrylate-based glue [12], collagen or fibrin glues [13], click chemistry-based glues [14], and, more recently, adhesive ceramics [15][16][17]. While naturally derived adhesives, such as fibrin glue (Tisseel), are cyto-and biocompatible and may retain biologic elements that enhance healing, their bond strengths KiloPascal (KPa) are relatively poor compared to the properties of cancellous and cortical bone [11,18].…”

Factors That Determine the Adhesive Strength in a Bioinspired Bone Tissue Adhesive

“…(A) Different curing environments (phosphate-buffered saline (PBS), water, or 100% humidity) and grip duration (24 h, blue box; or 5 min, red box) before curing did not affect the adhesive strength of 27% PMC (from left to right: groups #1, 4, 2, 5, 3, 6). (B) When the grip duration was shortened and the grip force reduced to mimic clinical conditions, comparable adhesive strength was observed in all samples except the automated mixing sample (red border) and low grip force (3 N) samples gripped for 5 min (from left to right: groups #3, 9,6,10,7,11,8,12,33,34; the red border indicates high speed mixing; green border indicates bone samples). (C) Different mole ratios of phosphoserine to αTCP, and cure conditions, affected adhesive strengths (from left to right: groups #3, 14, 15; 19-21; 13, 16-18) (100% humidity samples were gripped for 1 min).…”

“…Coacervation and nanoscale electrostatic interactions are also sufficient to create relatively strong tissue adhesion [4][5][6][7]. Recently, strong adhesion has been created in biomaterials that are not adhesive (bioceramics) by incorporating a modified amino acid (phosphoserine) [8][9][10]. Phosphoserine-modified cements (PMCs) display a unique microstructure, appearing amorphous rather than crystalline [10], can stabilize bioactive phases and remodel into precursors of hydroxyapatite [11], and display significantly improved healing, compared to unmodified cements [12][13][14][15].…”

“…The mechanical properties of PMCs have been well described [8,10]. In contrast, PMC adhesive strength has not been investigated under varied test conditions, and in situations mirroring clinical complications (e.g., very uneven adhesive bond thickness).…”