Biocompatibility of adhesive complex coacervates modeled after the sandcastle glue of Phragmatopoma californica for craniofacial reconstruction

Abstract

Craniofacial reconstruction would benefit from a degradable adhesive capable of holding bone fragments in three-dimensional alignment and gradually being replaced by new bone without loss of alignment or volume changes. Modeled after a natural adhesive secreted by the sandcastle worm, we studied the biocompatibility of adhesive complex coacervates in vitro and in vivo with two different rat calvarial models. We found that the adhesive was non-cytotoxic and supported the attachment, spreading, and migration of a commonly used osteoblastic cell line over the course of several days. In animal studies we found that the adhesive was capable of maintaining three-dimensional bone alignment in freely moving rats over a 12 week indwelling period. Histological evidence indicated that the adhesive was gradually resorbed and replaced by new bone that became lamellar across the defect without loss of alignment, changes in volume, or changes in the adjacent uninjured bone. The presence of inflammatory cells was consistent with what has been reported with other craniofacial fixation methods including metal plates, screws, tacks, calcium phosphate cements and cyanoacrylate adhesives. Collectively, the results suggest that the new bioadhesive formulation is degradable, osteoconductive and appears suitable for use in the reconstruction of craniofacial fractures.

Lessons from Sea Organisms to Produce New Biomedical Adhesives

“…Moreover, it was found that the highly condensed complex coacervates significantly increased Figure 12.5 Potential medical applications of adhesive materials inspired by mussels (blue), tube worms (red), and brown algae (green). (A) Bone adhesive for the reconstruction of craniofacial features [67], (B) adhesive-coated vascular scaffold promoting endothelial cell proliferation [68], (C) vascular sealant for surgical adjunctive leakage control [69], (D) adhesive for immobilization of pancreatic transplants on liver surface [70], (E) adhesive-coated biologic meshes for hernia repair [71], (F) sealant for fetal membrane repair [72], (G) adhesive-coated titanium bone implant promoting osteoblast proliferation [66], (H) adhesive for skin incision closure [73], and (I) adhesive-coated biologic scaffold for Achilles tendon repair [74]. All these biomimetic adhesives have been successfully tested in vitro with cultured cells or in vivo in animal models.…”

“…Moreover, a biodegradable version of the adhesive coacervate was designed by replacing the APMA/acrylamide copolymer by an amine-modified collagen hydrolysate [86]. This adhesive coacervate was used to repair rat calvarial bone defect and was capable of maintaining three-dimensional bone alignment in freely moving rats over a 12 week indwelling period [67]. Histological evaluation demonstrated that the adhesive was gradually resorbed and replaced by new bone with an inflammatory response commensurate with normal wound healing.…”

“…Histological evaluation demonstrated that the adhesive was gradually resorbed and replaced by new bone with an inflammatory response commensurate with normal wound healing. This noncytotoxic degradable coacervate therefore appears to be suitable for use in the reconstruction of craniofacial features (Figure 12.5) [67].…”

Cryopreserved human amniotic membrane and a bioinspired underwater adhesive to seal and promote healing of iatrogenic fetal membrane defect sites

“…In that study, the synthetic adhesive was shown to be non-cytotoxic using live ex vivo human amniotic membranes. A similar condensed polyelectrolyte adhesive formulation was biocompatible and effectively secured and maintained alignment of rat skull fragments during healing 20 .…”

Localization of the bioadhesive precursors of the sandcastle worm, Phragmatopoma californica (Fewkes)

“…These qualities have sparked interest in the sandcastle worm glue (Shao et al, 2009), as well as in other marine bioadhesives, notably the byssal adhesive plaques of mytilid mussels , as sources of natural materials and design principles for underwater adhesives. The potential applications of these bioinspired synthetic adhesives include the repair of wet living tissues (Winslow et al, 2010;Lee et al, 2011).…”