The use of osteoconductive bone graft substitutes in orthopaedic trauma

Several bone graft substitutes are now available for use in augmenting bone healing following trauma. Many of these products are osteoconductive and are indicated for filling bone defects in conjunction with standard methods of internal and external fixation. Osteoconduction refers to a process in which the three-dimensional structure of a substance is conducive for the ongrowth and/or ingrowth of newly formed bone. Currently used bone graft substitutes that primarily offer osteoconductive properties include coralline hydroxyapatite, collagen-based matrices, calcium phosphate, calcium sulfate, and tricalcium phosphate. These products vary considerably in chemical composition, structural strength, and resorption or remodeling rates. Understanding these differences is important in selecting a bone graft substitute with the properties desired for a specific clinical situation. The limited number of clinical studies and lack of direct-comparison studies between these products require the surgeon to fully understand the properties of each product when choosing a bone graft substitute.     

Osteoinductive bone graft substitutes

This review will summarize the major efforts currently underway to develop osteoinductive bone graft substitutes for minimally invasive spine fusions. The primary categories of substitute include purified bone growth factors, recombinant bone growth factors, and growth factors delivered by gene therapy approaches. Clinical trials are underway for the purified and recombinant bone growth factors and pre-clinical studies have yielded promising results for a variety of gene therapy techniques for generating bone.     

Osteoinductive bone graft substitutes

This review will summarize the major efforts currently underway to develop osteoinductive bone graft substitutes for minimally invasive spine fusions. The primary categories of substitute include purified bone growth factors, recombinant bone growth factors, and growth factors delivered by gene therapy approaches. Clinical trials are underway for the purified and recombinant bone growth factors and pre-clinical studies have yielded promising results for a variety of gene therapy techniques for generating bone.     

Synthetic bone graft substitutes

Replacement of extensive local bone loss is a significant clinical challenge. There are a variety of techniques available to the surgeon to manage this problem, each with their own advantages and disadvantages. It is well known that there is morbidity associated with harvesting of autogenous bone graft and limitations in the quantity of bone available. Alternatively allografts have been reported to have a significant incidence of postoperative infection and fracture as well as the potential risk of disease transmission. During the past 30 years a variety of synthetic bone graft substitutes has been developed with the aim to minimize these complications. The benefits of synthetic grafts include availability, sterility and reduced morbidity. The present article examines the relevance of synthetic bone graft substitutes, their mechanical properties and clinical application.     

Coralline bone graft substitutes.

Coralline porous ceramics are biocompatible and osteoconductive implants. They have proven to be effective as bone graft substitutes in large animal models and in humans. Bone and supporting soft tissue grow into and throughout their porosity if the implant is placed in direct apposition to viable bone and the interfaces are stabilized. The bone within the implant remodels in response to Wolff's law. Both the implant properties (chemistry and porosity) and the biologic environment modulate the rate of implant resorption. Composite technology with resorbable polymers can improve the mechanical properties of these ceramics.     

Bone repair techniques, bone graft, and bone graft substitutes

This paper reviews the techniques and materials (bone graft and bone graft substitutes) that currently are used to treat nonunions and bone defects. The techniques reviewed are intramedullary nailing, plating, distraction osteogenesis, and electric stimulation. Bone graft and bone graft substitutes reviewed are as follows: vascularized bone transfers; autogenous bone graft; autogenous bone marrow; dimineralized bone matrix; growth factors; calcium sulphate; calcium phosphates; and allograft. The goal of management of fractures, nonunions, and segmental bony defects, is the return of function as quickly and completely as possible. Techniques and management strategies constantly are evolving to accomplish this goal. This paper reviews the history, indications, and limitations of bone repair techniques, methods of bone grafting, and materials available as bone graft substitutes.     

人工骨生物材料的研究进展

在骨科领域,由于严重创伤、骨肿瘤、骨髓炎等多种原因所致的骨缺损十分常见,采取何种材料、以何种方式进行骨移植术,一直是人类几个世纪以来不断深入研究的重要课题。然而迄今为止,临床上对大范围骨缺损的治疗仍是较为棘手的难题。自体骨虽然是理想的骨缺损修复材料,但自体取骨增加了患者的创伤和痛苦,并且供骨的来源有限,难以满足大段骨移植的要求;同种异体骨因存在免疫排斥反应,可能传播疾病和术后并发症而受到限制;     

Clinical applications of bone graft substitutes

Autogenous bone grafting remains the gold standard for osseous reconstruction in clinical practice. It is associated with several limitations. The search for an alternative bone graft substitute with combined osteoinductive, osteoconductive, and osteogenic properties continues. This article highlights the properties of the various bone grafting materials currently available and discusses their efficacy in clinical practice.     

Allograft bone matrix versus synthetic bone graft substitutes

Autologous bone is used very often in the treatment of fresh fractures, delayed unions and non-unions. Alternatives have included allografts and in recent years also demineralized bone matrix. The growing availability of good synthetic bone grafts and their advantages in safety and avoiding donor-site morbidity are the reasons that these products are being used more and more. There are on the market a wide variety of substitutes with different capabilities. Nevertheless autologous bone graft is still considered as the gold standard and will be discussed here in that context. Osteoconductive, osteogenic and osteoinductive products will also be classified and their advantages and disadvantages described.     

Hydroxyapatite and tricalcium phosphate bone graft substitutes

Autografts have consistently outperformed calcium phosphate implants in most experimental models and clinical applications. However, human trials in metaphyseal defects demonstrate comparable results with autograft, hydroxyapatite, and TCP. Diaphyseal fractures and segmental defects represent more challenging problems, with less predictable results achieved with the synthetic bone graft substitutes. Improvements in the pore configuration, mechanical properties, and osteoinductive capacity of these implants should widen their future clinical application.     

Cellular bone matrices: viable stem cell-containing bone graft substitutes

Background contextAdvances in the field of stem cell technology have stimulated the development and increased use of allogenic bone grafts containing live mesenchymal stem cells (MSCs), also known as cellular bone matrices (CBMs). It is estimated that CBMs comprise greater than 17% of all bone grafts and bone graft substitutes used.PurposeTo critically evaluate CBMs, specifically their technical specifications, existing published data supporting their use, US Food and Drug Administration (FDA) regulation, cost, potential pitfalls, and other aspects pertaining to their use.Study designAreview of literature.MethodsA series of Ovid, Medline, and Pubmed-National Library of Medicine/National Institutes of Health (www.ncbi.nlm.nih.gov) searches were performed. Only articles in English journals or published with English language translations were included. Level of evidence of the selected articles was assessed. Specific technical information on each CBM was obtained by direct communication from the companies marketing the individual products.ResultsFive different CBMs are currently available for use in spinal fusion surgery. There is a wide variation between the products with regard to the average donor age at harvest, total cellular concentration, percentage of MSCs, shelf life, and cell viability after defrosting. Three retrospective studies evaluating CBMs and fusion have shown fusion rates ranging from 90.2% to 92.3%, and multiple industry-sponsored trials are underway. No independent studies evaluating spinal fusion rates with the use of CBMs exist. All the commercially available CBMs claim to meet the FDA criteria under Section 361, 21 CFR Part 1271, and are not undergoing FDA premarket review. The CBMs claim to provide viable MSCs and are offered at a premium cost. Numerous challenges exist in regard to MSCs' survival, function, osteoblastic potential, and cytokine production once implanted into the intended host.ConclusionsCellular bone matrices may be a promising bone augmentation technology in spinal fusion surgery. Although CBMs appear to be safe for use as bone graft substitutes, their efficacy in spinal fusion surgery remains highly inconclusive. Large, nonindustry sponsored studies evaluating the efficacy of CBMs are required. Without results from such studies, surgeons must be made aware of the potential pitfalls of CBMs in spinal fusion surgery. With the currently available data, there is insufficient evidence to support the use of CBMs as bone graft substitutes in spinal fusion surgery.     

骨移植替代材料在加速骨折治疗中的应用

具有骨不连倾向的高能骨折,传统的治疗方法是先切开复位内固定,待骨不连发生后,再植骨治疗。这一方法的最大缺点是治疗周期长,二次手术增加了患者的痛苦,且并发症高,不利于早日康复。C harnley早在1961年就提出对此类骨折应早期植骨,以缩短骨愈合时间。近年来,自体骨因取骨量受限、供骨区并发症高,一些生长因子、生物陶瓷以及复合材料等骨移植替代材料,已成为替代自体骨加速骨愈合的早期植入材料。     

Comparative performance of three ceramic bone graft substitutes.

BACKGROUND CONTEXT: A number of different synthetic calcium-based bone graft substitutes (BGS) are currently available for clinical use. There is, however, a lack of comparative performance data regarding the relative efficacy of these materials when placed in an osseous defect site. PURPOSE: To compare the rate, quality, and extent of osseous healing in a standard rabbit defect model for three commercially available BGS materials by measuring early bone formation and completion of defect healing and to identify whether rapid scaffold resorption stimulated or impaired bone healing. STUDY DESIGN: Osteochondral defects, 4.8 mm in diameter and 6 to 7 mm deep, were made through the articular surface into the subchondral bone of the femoral condyle of New Zealand White rabbits and filled with cylindrical pellets of one of three commercially available BGS materials: dense calcium sulfate (DCaS), ultraporous tricalcium phosphate (beta-TCP), and porous silicated calcium phosphate (Si-CaP). The repair response was examined at 1, 3, 6, and 12 weeks after surgery (n=4 per BGS per time point). METHOD: Qualitative histological and quantitative histomorphometric (% new bone, % bone graft substitute, capillary index, and mineral apposition rates) analysis. RESULTS: Rapid resorption of D-CaS, primarily through dissolution, elicited a mild inflammatory response that left the defect site empty before significant quantities of new bone were formed. Both beta-TCP and Si-CaP scaffolds supported early bone apposition (<1 week). However, beta-TCP degradation products subsequently provoked an inflammatory response that impaired and reversed bone apposition within the defect site. The Si-CaP scaffolds appeared to be more stable and supported further bone apposition, with the development of an adaptive bone-scaffold composite; cell-mediated resorption of scaffold and new bone were observed in response to local load and contributed to the production of a functional repair within the defect site. CONCLUSIONS: Rapid BGS resorption impaired the regenerative ability of local bone via three pathways: 1) insufficient persistence of an osteoconductive scaffold to encourage bone apposition, 2) destabilization of early bony apposition through scaffold disintegration, and 3) stimulation of an inflammatory response by elevated levels of particulate degradation products. This had a significant impact on the ultimate rate of healing. D-CaS did not stimulate early bone apposition, but bone repair was more advanced in D-CaS-treated defects at 12 weeks as compared with those treated with beta-TCP, despite the beta-TCP supporting direct bone apposition at 1 week. Si-CaP appeared to provide a more stable osteoconductive scaffold, which supported faster angiogenesis and bone apposition throughout the defect site, with the development of a functionally adaptive trabecular structure through resorption/remodelling of both scaffold and new bone. There was rapid formation of mineralized tissue at week 1 within the center of the defect and complete infiltration with dense, predominantly mature bone by weeks 3 to 6. The progressive remodeling of bone ingrowth and scaffold to reflect the distribution of local host tissue, combined with histological evidence of targeted osteoclastic resorption of both scaffold and bone, suggest that bone adaptation within the scaffold could be in response to Wolff's law. Although this model may not directly translate to a spinal fusion model and the products may vary according to the environment, these results suggest that, in patients in whom bone regeneration may be compromised, the degradation observed with some resorbable bone grafts may contribute to the decoupling of bone regeneration and resorbtion within the graft site, which may ultimately lead to incomplete bone repair.     

Coralline hydroxyapatite bone graft substitutes: radiographic evaluation.

The authors discuss a recently described bone graft material substitute derived from sea corals. They briefly review its background leading to the potential for clinical use. Radiologic evaluation is provided, with attention directed to its characteristics, compared with other bone grafts.     

Calcium phosphate ceramics as bone graft substitutes in filling bone tumor defects

Background:

Synthetic bio-inert materials are currently used as an alternative to autogenous bone graft. Calcium hydroxyapatite (HA) and Beta tri-calcium phosphate (β-TCP), which belong to the calcium phosphate ceramics group, are biocompatible and osteo-conductive. The purpose of this study is to analyse the use of HA and β-TCP in their ceramic forms as a bone graft substitute in filling bone voids after curettage of benign bone tumors.

Materials and Methods:

Twenty-four patients in the age range of 3.5-55 years (mean 14.3 years) having benign bone tumors with bone defects were filled with bone graft substitute following curettage. In 20 patients bone defects were filled with block/granules of HA ceramic and in four with β-TCP. Fibular strut graft was packed with HA in four patients. The patients were followed up for an average of 18 months (range 12-36 months).

Results:

The functional status of the patients at follow-up was evaluated and compared with preoperative functional status. Early incorporation of graft substitutes became evident radiologically between 6 and 10 weeks (Stage I). Complete incorporation (Stage III) was observed in an average of nine months (6-18 months). Clinical healing was observed before radiological healing. The average time taken to return to preoperative function was 14 weeks. There was no recurrence of lesion or growth retardation.

Conclusion:

Calcium hydroxyapatite and β-TCP are excellent bone graft substitutes for autogenous bone graft in filling voids after curettage of benign bone tumors.     

Modern issues in bone graft substitutes and advances in bone tissue technology

Autogenous bone grafting is the gold standard in repair of bony defects, fracture nonunion, and promoting arthrodesis. The complications related to obtaining autogenous grafts can be significant, and numerous materials are now available for augmentation or substitution. Allograft materials are highly effective for most applications; however, the surgeon needs to be acutely aware of the source of the tissue, for some tissue banks still use unacceptable processing techniques that destroy the structural and osteoinductive capacities of the graft. DBM products are unregulated and serious concerns exist as to the distribution of inactive products as commercially available to the practicing surgeon. Pressure from the orthopedic community has caused some manufacturers to test their products for activity before distribution. Calcium-based ceramic materials are effective as osteoconductive agents and work well alone as bone void fillers; however, augmentation of these implants with osteoinductive materials should be considered for use in nonunions and arthrodesis. Composite materials that incorporate osteoinductive materials in osteoconductive scaffolds are promising. New technology in isolation and creation of recombinant human bone morphogenic proteins and growth factors, and in the application of autogenous stem cells are emerging as the future of bone grafting procedures.     

Bone graft substitutes

Today’s surgeon faces many situations that require bone grafting. Autologous bone is the traditional standard for treating conditions requiring bone graft. However, autologous bone grafting has drawbacks such as donor site morbidity and increased operative time. Graft substitutes for autologous bone are an appealing alternative. Substitutes include allograft, mineral composites, ceramics, mineral cements, bioactive glass, proteins, and growth factors. The use and availability of these products has expanded exponentially. The large number of alternatives available and the relative lack of quality information regarding their indications and effectiveness leave the surgeon desiring to use the products with a daunting task. This article provides the surgeon with an overview of the basic concepts of bone grafting and discusses the most commonly used bone-graft substitutes and their potential indications.     

Use of bone graft substitutes in lower extremity reconstructive surgery

Autologous iliac crest graft has been a standard source of supplementary bone for treating bony defects, fractures and arthrodeses. Bone graft substitutes have recently become widely available. This paper reports on the use of bone graft substitute in 28 patients that otherwise would have required an iliac crest graft. Twenty-four of the 28 operations were successful in the primary procedure with four patients requiring a second procedure that was then successful.