CORR Insights®: Deep-freezing Temperatures During Irradiation Preserves the Compressive Strength of Human Cortical Bone Allografts: A Cadaver Study

Where Are We Now?

Structural bone allografts remain a staple in the orthopaedic surgical toolkit for treating large bone defects [8]. But how we select the allografts remains quite variable. The bone allograft selection and processing industry in the United States is overseen by the United States Food and Drug Administration and American Association of Tissue Banks [9]. Their guidelines focus primarily on disease and neoplasm transmission prevention, usually through the use of gamma irradiation [8]. However, the use of gamma irradiation also has deleterious effects on the structural integrity of structural bone allografts, which is critical for long-term patient success [7].

We are still learning about the factors affecting structural bone allograft quality. In the current study by Yang Harmony et al. [13], the authors found that gamma irradiation of cortical bone specimens below -40°C preserved the mechanical properties of bone compared with higher temperatures. This study calls to attention the importance of bone-processing considerations in affecting structural allograft quality. One of the greatest challenges in utilization of structural allograft bone is donor heterogeneity. Therefore, it is critical to study bone-processing practices, which are within our control, and, as demonstrated by Yang Harmony et al. [13], can have a major impact on structural integrity and, likely, clinical outcomes.

Where Do We Need To Go?

With long-term failure rates of cortical structural allografts reaching 15% for fracture and 12% for nonunion [3], there is a need to scrutinize the structural allografts that we use. There is no consensus among tissue banks regarding donor bone inclusion criteria or bone processing [8]. There is considerable variation in gamma radiation for sterilization of bone, ranging from 15 kGy to 35 kGy [12]. Bone-processing practices that can improve sterilization and structural integrity should be standardized and routinely reevaluated.

Methods to quantify the structural integrity of bone allografts also need further investigation. Conventional donor criteria such as age have been found to not be correlated with allograft strength [6]. Nondestructive methods of bone quality evaluation should be investigated. For example, novel tools, such as Raman spectroscopy, offer promising ability to assess the inherent collagen and mineral quality of bone allografts nondestructively [1, 5]. Conventional monotonic tests are valuable but do not simulate the cyclic stress that these structural allografts experience [7]. We still need to determine whether models that better simulate the physiologic stress and environment that structural allografts will be subjected to after implantation into the human body may improve the accuracy of bone-processing practices and structural integrity.

Finally, long-term clinical follow-up should be performed to monitor the rates of disease transmission, surgical site infection, and fracture after implantation into patients.

How Do We Get There?

As Mark Twain once said, “History doesn’t repeat itself, but it often rhymes.” There are approaches from the history of polyethylene manufacturing in total joint arthroplasty that may be applicable to structural bone processing. The granular study of polyethylene wear has led to innovations such as inert gas sterilization and vitamin E treatment [4]. Although bone specimens are inherently heterogeneous, bone-processing practices can be controlled and should be closely scrutinized. Perhaps we can learn from the trails blazed in polyethylene manufacturing research and apply the lessons to allograft bone. To start, research into ideal irradiation dosages and irradiation mediums should be performed.

Heterogeneity of donor structural bone allografts are a challenge. Unlike total joint implants, structural bone allografts cannot be precision manufactured, and are therefore variable in quality. It is critical to identify and select bone allografts that have the best structural integrity as possible to decrease risk of failure once implanted in patients. Conventional measurements, such as cortical thickness, can play a role in this [6]. Novel mediums, such as Raman spectroscopy, which nondestructively assesses the inherent mineral, collagen, and water content of bone, are potential new screening tools to assess donor bone for structural integrity [1, 5]. We found that collagen quality, as assessed through Raman spectroscopy, accounted for 44% of variability in cortical bone cyclic fatigue life in vitro, and present a model that predicted cycles to failure [5], though this should be prospectively validated in vitro and in vivo.

The in vivo lifespan of structural bone allografts depends on their ability to resist crack initiation and propagation from cyclic stress, which can lead to failure well below monotonic yield strength, which conventional biomechanical testing predominantly relies on [7]. Biomechanical models that emulate cyclic stresses under physiologic conditions (aqueous environment at human body temperature) are currently being studied [7] and should be validated with in vivo performance.

Finally, the clinical outcomes of these structural allografts are the most important metric. Registry initiatives, such as the American Academy of Orthopaedic Surgeons joint replacement and musculoskeletal tumor registries, present opportunities to track the functional outcomes and allograft survivorship (fracture, nonunion) of patients who received structural allografts [2]. Ideally, the data generated through these initiatives will help create novel algorithms that aid in allograft selection and predict allograft lifespan [10, 11]. The implementation of wearables could provide data on activity levels that may further improve these models. The ultimate goal of these efforts is to aid in providing the most robust structural allografts possible for our patients.