Injectable and compression-resistant low-viscosity polymer/ceramic composite carriers for rhBMP-2 in a rabbit model of posterolateral fusion: a pilot study

Abstract

BackgroundThe challenging biological and mechanical environment of posterolateral fusion (PLF) requires a carrier that spans the transverse processes and resists the compressive forces of the posterior musculature. The less traumatic posterolateral approach enabled by minimally invasive surgical techniques has prompted investigations into alternative rhBMP-2 carriers that are injectable, settable, and compression-resistant. In this pilot study, we investigated injectable low-viscosity (LV) polymer/composite bone grafts as compression-resistant carriers for rhBMP-2 in a single-level rabbit PLF model.MethodsLV grafts were augmented with ceramic microparticles: (1) hydrolytically degradable bioactive glass (BG), or (2) cell-degradable 85% β-tricalcium phosphate/15% hydroxyapatite (CM). Material properties, such as pore size, viscosity, working time, and bulk modulus upon curing, were measured for each LV polymer/ceramic material. An in vivo model of posterolateral fusion in a rabbit was used to assess the grafts’ capability to encourage spinal fusion.ResultsThese materials maintained a working time between 9.6 and 10.3 min, with a final bulk modulus between 1.2 and 3.1 MPa. The LV polymer/composite bone grafts released 55% of their rhBMP-2 over a 14-day period. As assessed by manual palpation in vivo, fusion was achieved in all (n = 3) animals treated with LV/BG or LV/CM carriers incorporating 430 μg rhBMP-2/ml. Images of μCT and histological sections revealed evidence of bone fusion near the transverse processes.ConclusionThis study highlights the potential of LV grafts as injectable and compression-resistant rhBMP-2 carriers for posterolateral spinal fusion.

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

“…In a previous study, local delivery of rhBMP-2 from a PEUR scaffold showed complete bridging of the processes and nearly complete degradation at 8 weeks. 68 While a slowly degrading settable polymer reduces the induction of new bone formation, it may also protect the implant against premature AG resorption and loss of mechanical integrity. The effects of the polymer degradation rate on new bone formation will be assessed in future studies.…”

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

“…No graft failure was observed in any of the groups throughout the 12 weeks, suggesting that AG extenders exhibited sufficient compression-resistant properties. 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 ].…”

Biodegradable polyurethane scaffolds in regenerative medicine: Clinical translation review

“…The laboratory of Guelcher and collaborators has pioneered the use of biodegradable PUs in orthopedics and has published an appreciable body of work using biodegradable PU scaffolds in combination with osteogenic material such as nanocrystalline hydroxyapatite (nHA), bioactive glass, calcium phosphates, recombinant human bone morphogenetic protein-2 (rhBMP-2), and bone autograft in a variety of pre-clinical bone defect models. [140][141][142][143][144][145][146][147][148][149][150] Although they have utilized several formulations, their PU chemistry most often comprises lysine triisocyanate (LTI) reacted via hand mixing or mixed injection with a variety of polyols such as a polyester triol synthesized from glycerol, ε-caprolactone, glycolide, and D,L-lactide 141 or thioketal-diol (TKdiol) 140 to form poly(ester urethane) (PEUR) or poly(thioketal urethane) (PTKUR), respectively. The main difference between these two PU formulations is their mode of degradation.…”

“…While PEUR degrades by hydrolysis and oxidation in vivo, PTKUR degrades only in the presence of ROS‐producing cells. The PEUR, combined with MasterGraft™ (MG; Medtronic) ceramic mixture (85% β‐tricalcium phosphate/15% hydroxyapatite), served as a carrier for rhBMP‐2 in several pre‐clinical models ranging from small to large animals and has been used in femoral condyle plug defects, 141 posterolateral lumbar fusion, 142 and mandibular ridge augmentation 143,145,148 . In a femoral condyle plug defect in sheep, the PEUR‐MG without rhBMP‐2 did not heal as completely after 12–15 months as the ceramic alone or PEUR‐autograft scaffolds 141 .…”