| Developments in orthopedic biomaterials research are steadily emerging to challenge the standard use of allografts and autografts as the preferred options for the nearly half-million spinal fusion procedures and other bone grafts annually performed in the United States. Among recent product introductions, two companies are offering promising alternatives to longstanding bone grafting techniques. Orthovita Inc. manufacturers VITOSS, a â- tricalcium phosphate composite. Interpore Cross International produces Pro Osteon, a hydroxyapatite compound derived from marine coral.
Autogenous (autologous) bone has long been the preferred implant for most bone graft procedures in the United States. Autogenous bone was the graft source in approximately 60 percent of bone grafts in 1996, compared with 34 percent allograft and 7 percent other materials.1 Autogenous bone is a desirable graft source insofar as it provides a scaffold for osteoconduction, contains noncollagenous bone matrix proteins that stimulate osteoinduction, and incorporates progenitor stem cells for osteogenesis.
Despite its wide prevalence, however, the use of autograft material poses several disadvantages. At best, the need to harvest the autograft from the iliac crest, proximal tibia or distal femur presents the obvious drawbacks of the discomfort, time and expense of two procedures to accommodate the patient’s need for bone grafting. At worst, the initial harvesting procedure can precipitate chronic pain, significant blood loss, infection and other iatrogenic complications, prolonged hospital stay and recovery time. The second surgery also adds substantially to the cost of the overall bone graft process.
While cadaver-derived allograft, the second most frequent technique, precludes the need for a second surgery, the grafted bone may be incompatible with and ultimately rejected by the host bone. Allograft also presents some risk of viral infection. In addition, the effectiveness of allograft material is inconsistent. The processing of allograft tissue to lower contamination risk can also substantially degrade the biologic and mechanical properties initially present in the donated tissue. Moreover, an ample supply is not assured; processed and banked donor bone is not always available at the time of surgery.2
The inherent shortcomings of both autografts and allografts and considerable recent progress in bioscience have driven the development of important emergent technologies.
During the past 30 years a variety of synthetic bone graft substitutes has become available. Synthetic materials are currently used in only 10 percent of orthopedic procedures worldwide, yet the progress and evaluation of these products demonstrate the prospect of rapid evolution. Through preclinical and clinical trials, all of the synthetic materials available are being monitored.3
Biosynthetic and synthetic materials now available to orthopedic and spinal surgeons include demineralized bone matrix, collagen, ceramics, cements, and polymers, such as silicone and some acrylics. These materials can serve as a structure on which new bone can grow. Many of these materials then dissolve over time, leaving only new bone behind. The benefits of these synthetic grafts include availability, sterility and reduced morbidity.4 In the table below, Betz5 identifies the features of the various bone replacement options:
Emerging Products
Two of the graft materials options listed above—â-tricalcium phosphate composite and a derived hydroxyapatite compound—are represented by products recently approved in the U.S.
Orthovita, Inc. of Malvern Penn., manufactures VITOSS, a resorbable, â-tricalcium phosphate scaffold intended as bone void filler in trauma and spinal procedures. During 2000, Orthovita gained regulatory clearance for VITOSS in the U.S. from the FDA and CE Certification in the European Union. These regulatory approvals allow the company to market VITOSS for use as cancellous bone void filler for bony voids including the extremities, spine and pelvis. Marketing of the product in the U.S. began in 2001.
With the intromission of VITOSS, when healing begins, cellular activity initiates remodeling throughout the entire structure of the implanted material scaffold. A porous, fine-particle structure encourages the flow of blood and nutrients through the matrix which is gradually replaced by structured bone similar to adjacent trabecular bone. The matrix guides regeneration of host bone in three dimensions. The polyporosity of resorbable calcium phosphate allows interaction with host bone. Fine nano-particle composition enhances resorption, facilitating rapid, effective bone remodeling. VITOSS has a full range of pore sizes to allow optimum resorption, fluid communication and bone ingrowth. The use of this product rules out rejection since bone redevelopment is autologous. As new bone permeates the matrix, the VITOSS dissolves.
VITOSS is the first of a suite of products to apply synthetic bone graft technology to mainstream clinical practice that Orthovita plans to bring to market. The company describes CORTOSS as a high-strength, bone-bonding, self-setting composite engineered specifically to mimic the characteristics of human cortical bone. In 2001 the product gained CE Certification for use in screw augmentation procedures in the European Union and regulatory approval in Australia. In 2003 CE Certification expanded to vertebral augmentation including compression fractures caused by osteoporosis and invasive tumors.
In the U.S., the company gained investigational device exemption (“IDE”) approval from the FDA in 2002 and began enrolling patients in a pilot clinical study in the U.S. for the use of CORTOSS in vertebral augmentation using the vertebroplasty surgical technique. Patient enrollment in this pilot clinical study was completed in May 2003. A pilot clinical study in the U.S. is also under way for the use of CORTOSS in vertebral augmentation using the kyphoplasty surgical technique.
A third product, RHAKOSS, is under development as a synthetic bioactive bone-bonding, load-bearing pre-formed spinal implant product for use in spinal repair procedures including vertebral interbody fusion and spine reconstruction. Clinical studies are proceeding in Europe. The companty has also filed an IDE with the FDA seeking approval to initiate human clinical studies for the use of RHAKOSS in cervical spinal fusion.
Bone from the Sea
Another increasingly popular product that mimics natural bone material is a hydroxyapatite compound called Pro Osteon, made by Interpore Cross International, Irvine, Calif. The product is produced by treating a common, non-decorative form of marine coral with a patented chemical process that converts the coral to hydroxyapatite. The porous, interconnected structure of the coral remains intact, providing an ideal matrix through which new bone tissue can grow. One coral head weighing 150-200 pounds provides enough material for hundreds of bone grafts. 6
Pro Osteon’s interconnected, porous structure closely resembles the porosity of human cancellous or cortical bone. When placed in contact with viable bone the implant provides a strong natural foundation for new bone ingrowth and offers structural support during the healing process. Upon healing, the composite of bone and Pro Osteon is comparable in strength to the surrounding bone. 7
Pro Osteon is indicated for the repair of metaphyseal defects and long bone cysts and defects. The company advises that it should be used within one month of fracture. The product does not possess to support the reduction of a defect site prior to soft and hard tissue ingrowth Standard internal fixation techniques are required.
In a typical long bone application, an appropriately sized Pro Osteon block is fitted into the damaged area and stabilized with a metal plate, screws or some other form of internal fixation. This protects the bone graft area so it can grow strong and durable. Eventually, the Pro Osteon is replaced by bone, leaving the mended bone as strong as prior to fracture. Healing rates for Pro Osteon compare favorably to other products. Pro Osteon needs no special storage or handling. It is simply taken from the shelf and sculpted to fit the defect.8
Berkeley Products Offer Synthetic Options
Cem-Ostetic™, from Berkeley Advanced Biomaterials, Berkeley Calif., released outside the U.S. in 2002 and approved by the FDA for US market in 2003, is a neutral-pH bone putty that sets up quickly with marginal exothermic reaction (less than 4C). The product is available in doses ranging from 5cc to 30cc. Once mixed with water for 60 seconds, the Cem-Ostetic™ putty can be placed in contact with other fluids, bone chips, or demineralized bone matrix to enhance bone reconstruction.
The putty is compounded from pre-measured doses of water and powder and can be injected or formed into an implant. The product is indicated only for bony voids or gaps that are not intrinsic to the stability of the bone structure. The putty can be molded to specific shapes and placed into the bony void or gap (e.g., extremities, spine, pelvis, or cranium), or directly injected into it. This putty is biodegradable, biocompatible and provides ideal conditions for healing surrounding tissues. The Cem-Ostetic™ paste set in situ or ex situ provides an open void filler that can augment hardware to help support bone fragments during the surgical procedure. The set putty acts as a temporary support medium and is not intended to provide structural support during the healing process.
A second product, Bi-Ostetic™ is a synthetic bone filler tailored for slow resorbtion. Based on Tricalcium Phosphate (TCP) and Hydroxyapatite (HAP), Bi-Ostetic is formulated to enhance bone regeneration and provide optimal osteoconduction and complete bone ingrowth. The product is available either in granular form (cancellous, cortical or cortico-cancellous) or as blocks. The spongy Bi-Ostetic bioceramic granules resemble cancellous bone chips. Bi-Ostetic ranges in doses from 1cc to 60cc. The Bi-Ostetic implant is radio-opaque, biocompatible and resorbs in the body as bone ingrowth occurs.
Berkeley Advanced Biomaterials emphasizes the affordability of its products. According to Ken Trauner, MD, the company’s clinical director, "Bi-Ostetic™ gives surgeons a cost-effective alternative to other synthetic bone fill products on the market. With Bi-Ostetic™, Berkeley Advanced Biomaterials brings additional solutions to the operating room."
The company is also reportedly working to mix synthetic bones with chemotherapeutic compounds, antibodies and proteins to facilitate sustained drug release.
A Look Ahead
The biocompatibility, availability, reliability and cost savings provided by these and other emerging alternatives to traditional bone graft sources establish a compelling case for their growing use. It appears certain that the next several years will see a greatly expanded arsenal of synthetic products and technical advances that will bring revolutionary change to this mainstay of surgical practice.
1Boyce T, Edwards J. Scarborough N. Allograft bone: the influence of processing on safety and performance. Orthop Clin North Am. 1999; 30:571-581.
2Betz, Randal R., MD “Limitations of Autograft and Allograft: New Synthetic Solutions,” Orthopedics Journal, May 2002.
3D'Ambrosia, Robert D., MD, Supplemental Introduction, “Scaffolds, Cells, and Signals: Advances in Synthetic Bone Graft Materials for Orthopedic Surgery”, Orthopedics Journal, May 2002.
4 Moore WR, Graves SE, Bain GI, ANZ J Surg. 2000; 71: 354-361
5 Betz, Randal R., MD, op.cit.
6 http://www.arthroscopy.com/sp12013.htm
7 Vaccaro, Alexander R., MD, “The Role of the Osteoconductive Scaffold in Synthetic Bone Graft,” http://www.orthobluejournal.com/supp/0502/vaccaro/
8http://www.arthroscopy.com/sp12013.htm
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