Demineralized Bone Matrix (DBM) and Viscous Carriers: A Novel Approach to Bone Grafting

The Major Challenge of Bone Reconstruction

Reconstruction of large bone defects has always been one of the most challenging issues facing orthopedic surgeons. These defects are usually caused by severe trauma, removal of bone tumors, deep infections, or nonunion fractures. In such situations, surgeons need materials that can fill the lost bone space and stimulate the natural healing process.

Autograft Bone Grafting: The Gold Standard, but Not Perfect

Autograft bone, usually harvested from the iliac crest, is considered the “gold standard” of treatment. This approach simultaneously provides three critical properties: osteoconductivity (guiding bone growth), osteoinductivity (stimulating bone formation), and osteogenesis (production of new bone by living cells). However, this method is not without drawbacks. Harvesting bone from the pelvis requires an additional surgical procedure and may be associated with complications such as chronic pain, infection at the donor site, local numbness, and even pelvic fracture. In addition, the amount of bone that can be harvested is limited, and the shape of the harvested bone may sometimes not match the defect site. These limitations have led researchers and physicians to seek more suitable alternatives.

What Is Demineralized Bone Matrix (DBM)?

Demineralized bone matrix, or DBM, is a type of allograft bone graft (from another individual). It is generally produced by removing the mineral components of bone using acid, while retaining collagen, non-collagenous proteins, osteoinductive growth factors such as BMPs (bone morphogenetic proteins), and small amounts of residual minerals (between 1% and 6%). After this process, BMPs that were previously embedded within the mineral components are released and can exert their potential to stimulate new bone formation. The remaining collagen also provides a three-dimensional scaffold into which stem cells and new blood vessels can grow, supporting bone formation.

Advantages of Using DBM

Using DBM for bone reconstruction offers several advantages. First, there is no limitation on the amount of graft available, and large quantities can be obtained from bone banks. Second, it eliminates the need for a separate surgical procedure to harvest bone from the patient and the associated donor-site complications. Third, the demineralization process removes the original cells and potential bacteria present in the donated bone, which reduces the risk of immune rejection and infection. It also shortens surgical time and the patient’s recovery period.

History of DBM Use

The use of DBM dates back to 1889, when Sen first used demineralized bovine bone to repair skull and long-bone defects in humans. However, the major milestone occurred in 1965, when Urist and colleagues first used human-derived DBM to repair bone defects and lumbar spinal fusion. Since then, DBM has been increasingly used in orthopedic surgery, and extensive research has been conducted into its bone-regenerative capabilities.

Challenges of Using DBM Alone

Although DBM alone has osteoinductive and osteoconductive potential, using it as a powder or free particles presents several challenges. These particles have a loose structure and can easily disperse during surgery due to blood washout or irrigation fluids. In addition, filling irregular defects with prefabricated materials may leave dead space and result in nonunion or delayed healing. For this reason, today’s most popular DBM products are provided as moldable putties or pastes that can completely and firmly fill the defect site.

Viscous Carriers: A Solution for Adhesion and Moldability

To convert DBM powder into a usable putty, it is combined with biocompatible viscous carriers. These carriers should have the following properties: complete biocompatibility with body tissues (non-toxic, non-immunogenic, non-teratogenic, and non-carcinogenic), an appropriate biodegradation rate that is compatible with the bone-forming process, desirable viscosity and moldability, an osteoconductive three-dimensional microstructure, and optimal mechanical properties. Based on molecular weight, these carriers are generally divided into polymeric and low-molecular-weight groups.

Polymeric Carriers: Chitosan

Chitosan, derived from chitin (the main component of the hard exoskeleton of crustaceans and insects), is a linear polysaccharide with unique properties. It dissolves in acidic environments and can form porous sponges that are highly suitable for bone implantation. Chitosan is degraded in the body by the enzyme lysozyme, and its final products are non-toxic. Its degradation rate depends on the degree of deacetylation; forms with a high degree of deacetylation (more than 85%) degrade more slowly and remain in the body for months. One prominent feature of chitosan is its positive cationic charge, which attracts negatively charged proteoglycans and facilitates osteoblast adhesion. In addition, chitosan has antibacterial, antifungal, mucoadhesive, analgesic, and hemostatic properties and can be produced in various forms, including hydrogels, powders, microspheres, and nanofibers.

Hyaluronic Acid

Hyaluronic acid is a large linear molecule with unique viscoelastic properties that naturally occurs in various tissues of the body, including joints, the vitreous humor of the eye, synovial fluid, cartilage, and skin. Because it contains numerous carboxyl and hydroxyl groups, it has a high capacity for water retention and can absorb more than 400 times its own weight in water. Hyaluronic acid plays an important role in tissue repair and regeneration. Studies have shown that its hydrogels can retain BMPs and influence interactions between osteoclasts and osteoblasts, which are critical for bone regeneration and fracture healing. Most absorbed hyaluronic acid is ultimately broken down into monosaccharides and converted to carbon dioxide and water, without toxic effects on the body.

Sodium Alginate

Alginate is the most abundant marine biopolymer and is extracted from brown algae. It provides plants with the flexibility and strength needed for growth in the sea. Alginate polymers are unbranched linear chains composed of guluronic acid and mannuronic acid units. Only the guluronic acid blocks can form cross-links with divalent cations such as calcium, producing soft gels that underlie many applications of this material. Sodium alginate dissolves slowly in cold water and forms a viscous colloidal solution. Regarding alginate biocompatibility, studies have shown that, provided it has high purity, it has excellent compatibility with body tissues. The G/M ratio (mannuronic acid to guluronic acid) and molecular weight are important factors affecting biocompatibility.

Carboxymethyl Cellulose

Carboxymethyl cellulose, or CMC, is a derivative of plant cellulose that is widely used in the pharmaceutical industry. It is a white to off-white, odorless, slightly moisture-retaining powder that dissolves in water at all temperatures but is practically insoluble in organic solvents. CMC acts as a stabilizer, emulsifier, thickener, and adhesive and can retain water and form a protective film. One of its most important applications is its anti-adhesion property, which mainly acts through mechanical separation of tissues. This material can reduce fibroblast activity or proliferation, prevent fibrin deposition on injured serosal surfaces, and prevent plasminogen removal from the wound surface. CMC also has hemostatic properties and can reduce adhesion by regulating urokinase-type plasminogen activator and its cellular receptor.

Type I Collagen

Type I collagen is the most abundant protein in the mammalian body and accounts for more than 90% of the organic mass of bone. It is also the primary collagen in tendons, skin, ligaments, and many connective tissues. Type I collagen has a right-handed triple-helix structure composed of two alpha-1 chains and one alpha-2 chain. Because of properties such as biodegradability, low immunogenicity, induction of BMP-2 receptor expression, and the possibility of large-scale extraction, type I collagen is highly attractive for medical applications. It contributes to the capture, local storage, and delivery of growth factors and cytokines and plays an important role in organ development, wound healing, and tissue repair.

Poloxamer 407

Poloxamer 407 is a triblock copolymer consisting of a hydrophobic central block of polyoxypropylene and two hydrophilic side blocks of polyoxyethylene. At concentrations of 20–30%, its aqueous solution exhibits reverse thermal gelation: it is liquid at refrigerator temperature (4–5°C) but becomes a gel at body temperature. This unique property makes Poloxamer 407 an ideal carrier for injection because it can be injected as a cold liquid and then transform into a gel at the target site, retaining DBM within it. However, long-term use of Poloxamer 407 in mice has produced changes in lipid metabolism, indicating a need for further research.

Low-Molecular-Weight Carriers: Glycerol

Glycerol is a sweet, colorless, clear, odorless organic compound that is miscible in all proportions with water, alcohol, amines, and phenol. It has good biocompatibility and viscosity and is one of the most common viscous carriers for DBM. However, glycerol is water-soluble and may not be stable and may have toxic potential with extensive use. Nevertheless, clinical studies and published reports on glycerol-containing products have not reported serious adverse effects associated with it.

Calcium Sulfate

Calcium sulfate, commonly known as plaster, is an inorganic material with the formula calcium sulfate dihydrate. With controlled heating, it loses water and is converted into calcium sulfate hemihydrate (plaster of Paris), which has moldability and self-setting properties at the site. These properties make it suitable for filling and repairing bone defects. Calcium sulfate has a structure similar to bone, is osteoconductive, and is inexpensive. The exact mechanism by which calcium sulfate increases bone formation is not fully understood, but the release of calcium ions at the site is thought to stimulate osteoblast differentiation. In addition, local pH changes during dissolution may demineralize adjacent bone and release matrix-bound growth factors, thereby supporting bone formation. The biocompatibility of calcium sulfate has been demonstrated in numerous studies, and minimal inflammatory responses have been observed after implantation.

Bioactive Glass

Bioactive glass was developed by Hench in 1969 and has been used clinically since 1985. It has excellent biocompatibility and has not produced an inflammatory response in animal and human models. Bioactive glass is both osteoconductive and osteoinductive and can establish a strong chemical bond with bone. When bioactive glass is exposed to body fluids, its surface dissolves and releases calcium, phosphorus, and silicon ions. These ions lead to the formation of a silica gel layer on the surface, followed by deposition of amorphous calcium phosphate. Over time, this layer transforms into hydroxycarbonate apatite, which is essential for bonding to bone. Interestingly, bioactive glass can regulate important genes such as insulin-like growth factor and vascular endothelial growth factor, promoting osteoblast proliferation and increasing vascularization, which is essential for new bone formation.

Commercial DBM Products

Today, numerous commercial DBM products from different brands are available, each combined with a specific carrier.

Iranian Tissue Product, with a focus on the development and production of allograft products, operates in the field of providing tissue products for use in various medical and dental applications. The company uses specialized knowledge, advanced tissue-processing technologies, and quality standards to provide a diverse range of allograft products to healthcare professionals to support tissue repair and regeneration.

Within the allograft product portfolio of Iranian Tissue Product, DBM Putty is produced. This product is a demineralized bone matrix (DBM) provided as a putty and contains DBM particles smaller than 500 micrometers together with hyaluronic acid.

Iranian Tissue Product is a manufacturer of allograft products, including DBM Putty. DBM Putty is a demineralized bone matrix designed for bone reconstruction and repair applications, using DBM particles smaller than 500 micrometers together with hyaluronic acid.

Future Outlook

Despite significant advances in DBM and its viscous carriers, an ideal graft material that meets all the requirements of an excellent bone graft does not yet exist. In addition, different materials, different methods, and even identical processing conditions for DBM products can produce different osteogenic activity, and the optimal conditions for maximizing bone-forming capacity are still not fully understood. In the future, combining DBM with other materials such as bone-marrow-derived stem cells, mesenchymal stem cells, and new growth factors will be one of the major directions of research. The development of smart carriers capable of controlled growth-factor release, as well as the use of advanced technologies such as three-dimensional printing to create personalized scaffolds, will open new horizons for regenerative bone medicine.

Conclusion

Demineralized bone matrix combined with various viscous carriers is considered an available option for bone reconstruction. This technology, by reducing the complications associated with harvesting bone from the patient’s body and providing suitable moldability, has established its role in orthopedic surgery, particularly in spinal fusion, complex fracture repair, treatment of nonunion, and benign bone tumors. As research continues and new products are developed, DBM and its derivatives are expected to play an increasingly important role in regenerative medicine and transform the future of bone reconstruction.

Bone Allograft Products by Iranian Tissue Product

Iranian Tissue Product focuses on the processing and production of allograft products and offers a range of tissue-based products designed for bone reconstruction and regeneration. These products include various bone powders and bone particles, bone graft products, and DBM Putty. Each product is designed for specific bone regeneration applications based on its unique properties and characteristics.

For more information about the products and the features of each bone allograft, please visit the [Iranian Tissue Product Bone Allograft Products page].

Article Reference

Zhang H, Yang L, Yang XG, Wang F, Feng JT, Hua KC, Li Q, Hu YC. Demineralized Bone Matrix Carriers and their Clinical Applications: An Overview. Orthopaedic Surgery. 2019;11(5):725–737. doi:10.1111/os.12509.