Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness.

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The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence

The bio-mechanical phenomena occurring in bones grafted with the inclusion of artificial materials demand the formulation of mathematical models which are refined enough to describe their not trivial behavior. A 3D theoretical model, previously developed and used in 1D space, is employed to investigate and explain possible effects resulting from 2D interactions, which may not be present in 1D case so more realistic situations are approached and discussed. The enhanced model was used to numerically analyze the physiological balance between the processes of bone apposition and resorption and material resorption in a bone sample under plain stress state. The specimen was constituted by a portion of bone living tissue and one of bio-resorbable material and was acted by an in-plane loading condition. The signal intensity between sensor cells and actor cells was assumed to decrease exponentially with their distance; the effects of adopting two different laws, namely an absolute and a quadratic functions, were compared. Ranges of load magnitudes were identified within which physiological states are established. A parametric analysis was carried out to evaluate the sensitivity of the model to changes of some critical quantities within physiological ranges , namely resorption rate of bio-material, load level and homeostatic strain. In particular the spatial distribution of mass densities of bone tissue and of resorbable bio-material and their time evolution were considered in order to analyze the biological effects due to the parameter's changes. Synthetically, these biological effects can be associated to different ratios between bone and bio-material densities at the end of the process and to different delays in the bone growth and material resorption. These numerical analyses allowed for finding the most desirable situations in which a gradual resorption of the artificial graft occurs together with the simultaneous formation of new bone, finally leading to an almost complete substitution of the bio-resorbable material with living tissue.

https://hal.archives-ouvertes.fr/hal-00842604/document

A 2-D continuum model of a mixture of bone tissue and bio-resorbable material for simulating mass density redistribution under load slowly variable in time

https://www.materialstoday.com/download/51100/

Hydrogels in calcium phosphate moldable and injectable bone substitutes: Sticky excipients or advanced 3-D carriers?

The use of rabbits for experimental research has a long historical tradition. The aim of this review consists in outlining the use of the rabbit for research in implant dentistry and related tissue regeneration. Rabbits appear as a first-hand choice for fundamental implant design studies because of their size, easy handling, short life span, and economical aspects in purchasing and sustaining. In the following, the various anatomical sites in the rabbit will be summarized to provide an overview of current possibilities and limitations of this model for bone research in oral implantology.

The Rabbit as Experimental Model for Research in Implant Dentistry and Related Tissue Regeneration

To investigate the potential application of bone marrow stromal cells (BMSCs) and an injectable sodium alginate/gelatin scaffold for bone tissue engineering (BTE). The phenotype of osteogenic BMSCs was examined by mineralized nodules formation and type I collagen expression. Cell proliferation was evaluated by MTT assay. The biocompatibility of scaffold and osteogenic cells were examined by hematoxylin and eosin (H&E) staining. Ectopic bone formation as well as closure of rabbit calvarial critical-sized defects following scaffold-cell implantation were analyzed by histological examination and computed tomography (CT) scanning. Spindle-shaped osteogenic cells of high purity were derived from BMSCs. The osteogenic cells and sodium alginate/gelatin (2:3) scaffold presented fine biocompatibility following cross-linking with 0.6% of CaCl2. After implantation, the scaffold-cell construct promoted both ectopic bone formation and bone healing in the rabbit calvarial critical-sized defect model. Our data demonstrated that the sodium alginate/gelatin scaffold could be a suitable biomaterial for bone engineering, and the scaffold-osteogenic cells construct is a promising alternative approach for the bone healing process. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

Bone tissue engineering using bone marrow stromal cells and an injectable sodium alginate/gelatin scaffold.

Objectives. The aims of this study were to test whether or not the application of an in situ–formed synthetic polyethylene glycol hydrogel (PEG) used as a biodegradable membrane for guided bone regeneration with a variety of graft materials and ambient oxygen or hyperbaric oxygen (HBO) environments would result in enhanced bone regeneration, and to observe the histologic and histomorphometric aspects of bone healing of the calvarial defects with and without a PEG membrane. Study design. Thirty adult, skeletally mature, male New Zealand white rabbits were randomly divided into 3 groups of 10 animals each. Bilateral 15-mm-diameter critical-size defects were created in the parietal bones of each animal. Group 1 served as a control with unfilled bilateral calvarial defects, group 2 had bilateral calvarial defects filled with morcelized autogenous calvarial bone, and group 3 had bilateral calvarial defects filled with a biphasic calcium phosphate ceramic. One of the calvarial defects was randomly protected with a PEG resorbable liquid membrane in each animal. Five animals from each group underwent a course of HBO treatment (2.4 ATA 100% oxygen for 90 minutes 5 days a week for 4 weeks) and the other 5 served as control and did not receive any supplemental oxygen (normobaric). The animals were killed 6 weeks after their surgery, and their parietal bones were harvested. The specimens were analyzed with microscopic computerized tomography (microCT) scans and histomorphometrics. Results. The unfilled normobaric control bony defects did not heal, proving the critical-size nature of these defects. The presence of autogenous bone or bone ceramic in the defects increased the bone volume fraction and bone mineral density of the defects (P .001). The presence of a membrane in the ungrafted and autogenous bone grafted defects resulted in a decrease in the corrected bone volume fraction (P .002) but not in the bone ceramic grafted defects (P .580). Bony healing of defects where the membrane was unsupported was compromised; the membrane did not maintain the desired bone regeneration volume with the unfilled and autogenous bone grafted groups. The PEG resorbable liquid membrane worked best with the bone ceramic material. HBO did not ameliorate the healing of the autogenous bone graft or ceramic filled defects in the 6week time period of this study. Conclusions. Although the PEG resorbable liquid membrane is easy to use and forms an occlusive layer, caution is recommended when using the membrane over an unsupported defect. HBO did not ameliorate bony healing with the membrane at the early 6-week time point. The authors recommend future assessment with HBO at the 12-week time

Joel M. Davis

Papers

Bone healing with an in situ-formed bioresorbable polyethylene glycol hydrogel membrane in rabbit calvarial defects.