Cranial flap fixation in sheep using a resorbable bone adhesive

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>The authors’ goal in this study was to investigate the use of a novel, bioresorbable, osteoconductive, wet-field mineral-organic bone adhesive composed of tetracalcium phosphate and phosphoserine (TTCP-PS) for cranial bone flap fixation and compare it with conventional low-profile titanium plates and self-drilling screws.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>An ovine craniotomy surgical model was used to evaluate the safety and efficacy of TTCP-PS over 2 years. Bilateral cranial defects were created in 41 sheep and were replaced in their original position. The gaps (kerfs) were completely filled with TTCP-PS (T1 group), half-filled with TTCP-PS (T2 group), or left empty and the flaps fixated by plates and screws as a control (C group). At 12 weeks, 1 year, and 2 years following surgery, the extent of bone healing, local tissue effects, and remodeling of the TTCP-PS were analyzed using macroscopic observations and histopathological and histomorphometric analyses. Flap fixation strength was evaluated by biomechanical testing at 12 weeks and 1 year postoperatively.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>No adverse local tissue effects were observed in any group. At 12 weeks, the bone flap fixation strengths in test group 1 (1689 ± 574 N) and test group 2 (1611 ± 501 N) were both statistically greater (p = 0.01) than that in the control group (663 ± 385 N). From 12 weeks to 1 year, the bone flap fixation strengths increased significantly (p &lt; 0.05) for all groups. At 1 year, the flap fixation strength in test group 1 (3240 ± 423 N) and test group 2 (3212 ± 662 N) were both statistically greater (p = 0.04 and p = 0.02, respectively) than that in the control group (2418 ± 1463 N); however, there was no statistically significant difference in the strengths when comparing the test groups at both timepoints. Test group 1 had the best overall performance based on histomorphometric evaluation and biomechanical testing. At 2 years postoperatively, the kerfs filled with TTCP-PS had histological evidence of osteoconduction and replacement of TTCP-PS by bone with nearly complete osteointegration.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>TTCP-PS was demonstrated to be safe and effective for cranial flap fixation in an ovine model. In this study, the bioresorbable, osteoconductive bone adhesive appeared to have multiple advantages over standard plate-and-screw bone flap fixation, including biomechanical superiority, more complete and faster bony healing across the flap kerfs without fibrosis, and the minimization of bone flap and/or hardware migration and loosening. These properties of TTCP-PS may improve human cranial bone flap fixation and cranioplasty.</jats:p></jats:sec>

Gluing Living Bone Using a Biomimetic Bioadhesive: From Initial Cut to Final Healing

“…PSer in combination with tetracalcium phosphate (TTCP) was shown to have good long-term osseointegration and bioresorbability at 52 weeks in a lapine model ( Kirillova et al, 2018 ). The same cement used to fill cranial defects in sheep demonstrated new bone formation and increased strength at 12 weeks, and further osseoinegration and strength versus control at 1 and 2 year follow-up ( Foley et al, 2020 ). In a study of simulated canine mandible repair procedures, while control (unfractured bone) was strongest in mechanical testing, the fixation with TTCP + PSer glue showed promise with greater strength than dental wire when either was combined with dental composite ( Geddes et al, 2020 ).…”

A new bone adhesive candidate- does it work in human bone? An ex-vivo preclinical evaluation in fresh human osteoporotic femoral head bone

“…In addition, long term biocompatibility was shown in a lapine model up to 52 weeks for a similar class of PMC adhesive where tetra-calcium phosphate was used [15] . At 2 years PMC adhesive, in a large animal (ovine) model [16] , showed no adverse local effects, signs of infection or cytotoxicity in tissues either at or adjacent to implantation sites. It should be noted that at the time of writing there is no human tissue data that confirm these results to the appropriate ISO standards for genotoxicity, carcinogenicity and reproductive toxicity of the adhesive biomaterial and its degradation products.…”

In vitro and in vivo evaluation of a bio-inspired adhesive for bone fixation

“…Among them, Tetranite® adhesive (Revbio, Lowell, Massachusetts, United States), which is composed of TTCP and OPS, self-sets to a multiphasic solid within a few minutes. It was claimed to display high bone-to-bone and bone-to-metal adhesive strength in a wet environment, in addition to excellent bioresorbability, osteoconductivity, and biocompatibility (15,(18)(19)(20). Pujari-Palmer et al (16,(21)(22)(23)(24) have also reported a bone adhesive (OsStic ™ ), based on OPS, α-TCP and calcium metasilicate, with a similar performance as Tetranite®.…”

“…Several mechanical testing methods for evaluating the adhesive strength and the compressive resistance of bone adhesives in vitro/ ex vivo have been described (15,16,18,19,(37)(38)(39)(40), showing a wide range of bone bond strength values depending on the type of bone as well as bone condition and surface preparation. So far, biomimetic CPC/OPS glues have been evaluated in vivo mostly regarding their biocompatibility, osseointegration or bioresorbability (15,18,20,23,24). However, animal models used for assessing their in vivo e cacy are scarcely reported (41).…”