Guided bone regeneration

Overview
'Guided bone regeneration or GBR is a surgical procedure that uses barrier membranes to direct growth of new bone at sites having insufficient volumes or dimensions for function or prosthesis placement. GBR is similar to guided tissue regeneration (GTR) but is focused on development of hard tissues instead of soft tissues of periodontal attachment. At present, guided bone regeneration is predominantly applied in the oral cavity to support new hard tissue growth on an alveolar ridge to allow stable placement of dental implants. Used in conjunction with sound surgical technique, GBR is a reliable and validated procedure.

History
Use of barrier membranes to direct bone regeneration was first described in the context of orthopaedic research by Hurley et al., in 1959. . The theoretical principles basic to guided tissue regeneration were developed by Melcher in 1976, who outlined the necessity of excluding unwanted cell lines from healing sites to allow growth of desired tissues. Based on positive clinical results of regeneration in periodontology research in the 1980's, research began to focus on the potential for re-building alveolar bone defects using guided bone regeneration.

Basic Principles
'The PASS Principle' published by Wang & Boyapati is an acronym outlining the fundamental rationale and stages of successful barrier membrane regeneration, both for bone and other tissues, and is a guide to the physiological processes central in tissue regeneration.
 * 1) PRIMARY CLOSURE of the wound to promote undisturbed and uninterrupted healing
 * 2) ANGIOGENESIS to provided necessary blood supply and undifferentiated mesenchymal cells
 * 3) SPACE creation and maintenance to facilitate space for bone in-growth
 * 4) STABILITY of the wound to induce blood clot formation and allow uneventful healing

GBR in dentistry
The first application of barrier membranes in the oral cavity was by Nyman, Lindhe, Karring and Gottlow  in the context of regeneration of periodontal tissues via GTR, as an alternative to ressective surgical procedures to reduce pocket depths.

Types of Barrier Membranes Used
Barrier membranes have been derived from a variety of sources, both natural and synthetic, and are marketed under various trade names. Membranes used in GBR and grafting may be of two principal varieties, non-resorbable and resorbable.

Non-Resorbable Membranes
Historically, GBR and grafting techniques began with impractical millipore (paper) filter barriers. Expanded polytetrafluoroethylene (ePTFE) membranes were first used by Gottlow et al. which are non-resorbable but biocompatible synthetic polymer membranes of the Teflon trade name. Although ePTFE are considered the standard for membranes and excellent outcomes have been achieved with this material, it is desirable to both the clinician and patient to minimize risk by reducing the frequency of surgical intervention. Consequently, resorbable or bioabsorbable membranes have been developed to avoid the limitations of ePTFE, which must be surgically retrieved in 4-6 weeks and are often contaminated by bacteria through premature exposure, limiting potential increases in bone volume. Non-absorbable ePTFE membranes are still used clinically on a regular basis, and long-term studies have shown ePTFE GBR bone responds to implants like non-augmented naive bone.

Resorbable Membranes
Resorbable membranes are either animal-derived or synthetic polymers. They are gradually hydrolyzed or enzymatically degraded and therefore do not require a second surgical stage of membrane removal. Their sources are varied, beginning in early years with rat collagen, bovine collagen, ox cecum cargile membrane, polylactic acid, polyacetic acid, polyglycolic acid, polyglactin 910(Vicryl), synthetic skin (Biobrane) and freeze-dried dura mater. Recently developed synthetic membranes are often combinations of various materials.


 * 1) Collagen resorbable membranes -  Collagen membranes are of either type I or II collagen from bovine or porcine sources.  They are often cross-linked and resorbed between 4 - 38 weeks depending on the type.  Brands of collagen barriers include Biomend, Biomend Extend, OSSIX, Neomem, and Hypro-Sorb.   Collagen absorbable barrier membranes are being used more frequently for their specific advantages over non-absorbable ones.  They relieve the need for a second stage surgery, inhibit migration of epithelial cells and promote new connective tissue attachment, have low antigenic properties, and assist in haemostasis by platelet aggregation leading to early clot formation and wound stabilization.8,11  Collagen membranes may also facilitate primary wound closure via fibroblast chemotactic properties,11  even after membrane exposure.  Compared to ePTFE membranes, resorbable barriers allow for fewer exposures and therefore reduce the effects of infection on newly formed bone.   Use of collagen membranes in particular, with bone mineral as a support and space maintainer, has achieved predictable treatment outcomes.


 * 1) Synthetic resorbable membranes - Synthetic membranes may be polymers of lactic acid or glycolic acid.  Their ester bonds are degraded over 30-60 days, leaving free acids that may be pro-inflammatory.  The majority of studies consider synthetics comparable to other membranes like ePTFE and collagen, and one author has found synthetics clinically superior to collagen membranes.  There are several types of synthetics: Vicryl, Atrisorb, Atrisorb-FreeFlow, Arisorb-D, Resolut XT, Epi-Gide and Gore Resolut Adapt, each made predominantly of acid polymers.  In addition, Capset is a calcium sulphate derivative synthetic membrane.

The integrity of resorbable membranes over the healing period has been questioned, relative to the ePTFE membranes, however, Hammerle et al (2007) indicate that the barrier function of the collagen membranes does allow for bone regeneration, provided that it is used with appropriate case selection. Donos et al (2002) also indicates that synthetic resorbable membranes hold their barrier capabilities for at least 30 days after insertion. Appreciation of the clinical success or failure for a specific membrane type is difficult to derive, since most studies do not use appropriate controls or fail to separate data by which type resorbable membrane was used.