Bone Regeneration by Controlled Release of Bone Morphogenetic Protein-2: A Rabbit Spinal Fusion Chamber Molecular Study.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spine fusion surgery. However, high doses of rhBMP-2 delivered with absorbable collagen sponge (ACS) have led to inflammation-related adverse conditions. Polyelectrolyte complex (PEC) control release carrier can substantially reduce the rhBMP-2 dose and complication without compromising fusion. The molecular events underlying controlled release and their effects on spinal fusion remain unknown. In this study, a rabbit interbody spinal fusion chamber was designed to provide a controlled environment for profiling molecular events during the fusion process. Study groups included Group 1, PEC with 100 µg rhBMP-2; Group 2, ACS with 100 µg rhBMP-2; Group 3, ACS with 300 µg rhBMP-2; Group 4, autologous bone graft; and Group 5, empty chamber. Manual palpation, microcomputed tomography, and histological analysis showed that Group 1 and 3 achieved bone fusion, while the other groups showed no signs of fusion. Gene expression profiling showed robust induction of osteogenic markers in Groups 1 and 3, with modulated early induction of inflammatory genes in the PEC group. Delivery of 100 µg rhBMP-2 with ACS (Group 2) resulted in less upregulation of osteogenic genes, increased inflammatory genes expression, and upregulation of osteoclastic genes compared to Group 1. These results suggest that the manner of BMP-2 release at the interbody spinal defect site could dictate the balance of in-situ osteogenic and antiosteogenic activities, affecting fusion outcomes. The molecular evidence supports PEC for sustained release of BMP-2 for spinal interbody fusion, and the feasibility of employing this novel interbody spinal fusion chamber for future molecular studies. Impact Statement A radiolucent rabbit interbody spinal fusion chamber was developed to study the molecular events during spinal fusion process. The gene expression profile suggests that control release of bone morphogenetic protein-2 (BMP-2) resulted in lower inflammatory and osteoclastic activities, but elicited higher osteogenic activities, while burst release of BMP-2 resulted in predominantly inflammation and osteoclastogenesis with minimum osteogenic activity. This study provides the molecular evidence that underscores the regeneration outcomes from the two different BMP-2 delivery systems. This spinal fusion chamber could be used for future molecular studies to optimize carrier design for spinal fusion.

State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective.

Scaffold-based bone tissue engineering aims to repair/regenerate bone defects. Such a treatment concept involves seeding autologous osteogenic cells throughout a biodegradable scaffold to create a scaffold-cell hybrid that may be called a tissue-engineered construct (TEC). A variety of materials and scaffolding fabrication techniques for bone tissue engineering have been investigated over the past two decades. This review aims to discuss the advances in bone engineering from a scaffold material point of view. In the first part the reader is introduced to the basic principles of bone engineering. The important properties of the biomaterials and the scaffold design in the making of tissue engineered bone constructs are discussed in detail, with special emphasis placed on the new material developments, namely composites made of synthetic polymers and calcium phosphates. Advantages and limitations of these materials are analysed along with various architectural parameters of scaffolds important for bone tissue engineering, e.g. porosity, pore size, interconnectivity and pore-wall microstructures.

Cranioplasty after trephination using a novel biodegradable burr hole cover: technical case report.

OBJECTIVE AND IMPORTANCE: We have developed novel biodegradable polymer implants by using the rapid prototyping technology fused deposition modeling. Early results of a clinical pilot study for cranioplasty are presented. CLINICAL PRESENTATION: Five patients with the diagnosis of chronic subdural hematoma were included in the study. After trephination and evacuation of the subdural hematoma, burr holes (diameter, 14 mm) were closed using a biodegradable implant made of polycaprolactone. Implants were computer designed with an upper rim diameter of 16 mm and a 14 mm body diameter with a fully interconnected, honeycomb-like architecture of 400 to 600 microm in pore size. INTERVENTION: Postoperative computed tomographic scans indicated that the plugs were stably anchored in the osseous host environment with no fluid collection detectable. The postoperative course was uneventful, and patients were discharged after 5 days. Follow-up scans after 3, 6, and 12 months showed that the implants were well integrated in the surrounding calvarial bone with new bone filling the porous space. CONCLUSION: These novel polymer scaffolds made of the slow-degrading material polycaprolactone represent a suitable implant for closure of post-trephination defects.

Fused deposition modeling of novel scaffold architectures for tissue engineering applications.

Fused deposition modeling, a rapid prototyping technology, was used to produce novel scaffolds with honeycomb-like pattern, fully interconnected channel network, and controllable porosity and channel size. A bioresorbable polymer poly(epsilon-caprolactone) (PCL) was developed as a filament modeling material to produce porous scaffolds, made of layers of directionally aligned microfilaments, using this computer-controlled extrusion and deposition process. The PCL scaffolds were produced with a range of channel size 160-700 microm, filament diameter 260-370 microm and porosity 48-77%, and regular geometrical honeycomb pores, depending on the processing parameters. The scaffolds of different porosity also exhibited a pattern of compressive stress-strain behavior characteristic of porous solids under such loading. The compressive stiffness ranged from 4 to 77 MPa, yield strength from 0.4 to 3.6 MPa and yield strain from 4% to 28%. Analysis of the measured data shows a high correlation between the scaffold porosity and the compressive properties based on a power-law relationship.