Poly(Thioketal Urethane) Autograft Extenders in an Intertransverse Process Model of Bone Formation

Abstract

Iliac crest autograft (AG) is the gold standard for bone grafting. Due to the limited supply of autograft, synthetic materials such as ceramics and polymers have been proposed as AG extenders to minimize the volume of AG required for induction of new bone formation. However, the feasibility of reactive polymers for use as settable AG extenders has not been previously investigated. In this study, a reactive oxygen species-degradable poly(thioketal urethane) (PTKUR) was evaluated as a settable AG extender. AG was anticipated to enhance infiltration of cells into the defect and induce new bone formation. Histological analysis of a preliminary study in a rat femoral segmental defect model showed that cells infiltrated PTKUR/AG implants at 4 weeks. In a second experiment, implantation into an intertransverse process model of bone formation showed bone remodeling from the superior and inferior transverse processes. Histological analysis combining data from stains and fluorochrome injections showed lamellar bone formation ongoing near the base of the transverse processes after 8 weeks. Similar findings were observed for a second group, in which 35% of the AG was replaced with calcium phosphate granules. These observations highlight the potential of PTKUR for use as a settable AG extender.

Settable Polymeric Autograft Extenders in a Rabbit Radius Model of Bone Formation

“…In agreement with an earlier PTKUR-AG study in a biologically stringent intertransverse process defect [ 39 ], residual polymer was observed in PTKUR-AG extenders at 12 weeks. PEUR degradation occurred more rapidly than PTKUR degradation, as evidenced by significantly less residual polymer within the defect at 12 weeks.…”

“…Previous studies in the spine and mandible demonstrated that an elastic modulus >1 MPa provided compression-resistant properties [ 46 , 47 ]. We previously reported PTKUR-AG and PEUR-allograft moduli of 6.08 MPa and 4.38–9.47 MPa, respectively [ 39 , 48 ].…”

“…PTKUR- and PEUR-AG extenders were fabricated by adapted two-component reactive-liquid molding methods as previously described [ 39 ]. Briefly, polyisocyanate comprised of either TK diol or polyester triol, 10 pphp iron acetylacetonate (FeAA) catalyst in ϵ-caprolactone 0.5% ( w / w ), and LTI-PEG prepolymer were mixed together.…”

“…Previous work has demonstrated selective, cell-mediated, first-order degradation of PTKUR in vivo [ 38 ]. Furthermore, low-porosity PTKURs utilized in rabbit intertransverse processes [ 39 ] and femoral plugs [ 33 ] exhibited new bone formation, but minimal PTKUR degradation was observed. Slow degradation is advantageous in applications in which mechanical stability is required; however, in applications utilizing biologics, faster graft resorption is necessary to harness the osteoinductivity.…”

In vitro cytocompatibility testing of oxidative degradation products

“…Polymers have also been designed to degrade upon exposure to reactive oxygen species for use in drug delivery, biosensing, and tissue engineering applications. 8,[23][24][25][26][27] The methods described here could be used to evaluate degradation products from these systems for toxicity or for their impact on the desired outcomes after implantation. These methods may also be useful in evaluating other polymers that may degrade by oxidation as one of multiple mechanisms as is proposed of some other polyurethane scaffolds and poly (ethylene glycol) hydrogels.…”