Periosteum- a Breakthrough in Tissue Engineering

Reconstruction of lost tissues is a long cherished goal in medical field. A lot of research has been done in the past (Finley et al 1978, Reyenders et al 1998, Reyenders et al 1999), and still is going on to explore tools and techniques for regeneration of lost tissues as a result of the disease process. The use of various grafts and recent tissue engineering techniques including stem cell research are testimony to the ever increasing need for most suitable treatment option to replace/repair lost tissues due to various pathologic processes.
Use of autogenous periosteum in general medical treatment has been extensive and has shown promising results (Reyenders et al 1999); on the contrary in dentistry, the use of periosteum as a regenerative tool has been limited and highly underrated; therefore, the purpose of this paper is to highlight the current status of use of periosteum in dentistry as well as suggesting its future use in various treatment options related specifically to dental field.
The periosteum is a highly vascular connective tissue sheath covering the external surface of all the bones except for sites of articulation and muscle attachment (Provenza 1986). The periosteum comprises of at least two layers, an inner cellular or cambium layer, and an outer fibrous layer (Finley et al 1978). The inner layer contains numerous osteoblasts and osteoprogenitor cells, and the outer layer is composed of dense collagen fiber, fibroblasts, and their progenitor cells (Orban et al 2002); osteogenic progenitor cells from the periosteal cambium layer may work with osteoblasts in initiating and driving the cell differentiation process of bone repair characterized by the development of the initial fracture callus and subsequent remodeling.
Periosteum can be described as an osteoprogenitor cell containing bone envelope, capable of being activated to proliferate by trauma, tumors, and lymphocyte mitogens (PT Tran Van et al 1982). Research on the structure of periosteum has shown that it is made up of three discrete zones (Squier 1990).
Zone 1 has an average thickness of 10–20um consisting predominantly of osteoblasts representing 90% of cell population, while collagen fibrils comprise 15% of the volume. The majority of cells in zone 2 are fibroblasts, with endothelial cells being most of the remainder. Zone 3 has the highest volume of collagen fibrils and fibroblasts among all the three zones. Fibroblasts take up more than 90% of the cells in zone 3. The morphology of fibroblasts is variable across the three zones.
The structure of periosteum varies with age. In infants and children it is thicker, more vascular, active, and loosely attached as compared to adults where it is thinner, less active, and firmly adherent (Fan et al 2008). In all age groups, the cells of the periosteum retain the ability to differentiate into fibroblasts, osteoblasts, chondrocytes, adipocytes, and skeletal myocytes. The tissues produced by these cells include cementum with periodontal ligament fibers and bone.
The periosteum has a rich vascular plexus and is regarded as the “umbilical cord of bone” ( Chanavaz et al 1995). The vasculature system of the periosteum was first studied in detail by Zucman and later by Eyre-Brook (Eyre Book 1984). Bourke’s studies showed that the capillaries supplying blood to bone reside within the cortex linking the medullary and periosteal vessels; a recent study has even shown that periosteal cells release vascular endothelial growth factor (Bourke et al 2003 ) which promote revascularization during wound healing. Recently, studies have reported the existence of osteogenic progenitors, similar to mesenchymal stem cells (MSCs), in the periosteum (Tenenbaum et al 1985, Zohar et al 1997).
Under the appropriate culture conditions, periosteal cells secrete extracellular matrix and form a membranous structure (Mizuno et al 2006 ).The periosteum can be easily harvested from the patient’s own oral cavity, where the resulting donor site wound is invisible. Owing to the above reasons, the periosteum offers a rich cell source for bone tissue engineering; hence, the regenerative potential of periosteum is immense.
Developing bone substitutes for bone defect repair has inspired orthopedic surgeons, bone biologists, bioengineering researchers to work together in order to design and develop the promising products for clinical applications. Duhame in the year 1742 can be considered the first investigator to study the osteogenic potential of periosteum (Iilutmacher et al 2003). A century later, another French surgeon, Ollier, discovered that the transplanted periosteum could induce de novo bone formation.
One of the earliest experimental studies to demonstrate osteogenic potential of periosteum was that of Urist and McLean who reported that periosteum produced bone when transplanted to the anterior chamber of the eye of the rat (Urist et al 1952). Skoog subsequently introduced the use of periosteal flaps for closure of maxillary cleft defects in humans; he reported the presence of new bone in cleft defects within 3–6 months following surgery (Skoog et al 1985). Since then, surgeons have reported the successful use of maxillary periosteal flaps (O’Brien et al 1970, Rintala 1989) as well as periosteal grafts from the tibia or rib.
Melcher observed that new bone laid down in parietal bone defects of rats and was deposited by periosteum that had not been previously elevated or disturbed in any other way (Melcher et al 1969), while other investigators have suggested that the contact between the periosteal flap or graft and the underlying bone is crucial to stimulation of osteogenesis (Cestero et al 1975, Rauch et al 2007 ). More recently, the osteogenic/chondrogenic capacity of periosteum and related mechanisms have been confirmed, and the underlying biology is better understood through a number of studies (Seeman et al, 2003, Emans et al 2005, Eyckmans et al 2006, Tadjiargyrou et al 2000, Romana et al 1990, Iwasaki et al 1995, Sakata et al 2006, Wiesmann et al 2003, Zhang et al 2005).
The use of periosteums as Guided Tissue Regeneration has been suggested by many studies , although long-term results are still awaited to establish the regular and the most effective use of periosteal grafts as barrier membranes. The need for a graft, which has its own blood supply, which can be harvested adjacent to the recession defect in sufficient amounts without requiring any second surgical site and has a potential of promoting the regeneration of lost periodontal tissue is a long-felt need. The use of periosteum can revolutionize the success of various dental treatments which require either bone or soft tissue regeneration; particularly the future use of periosteum must be explored in periodontal and implant surgical procedures.

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