Autografts—that is, autogenous grafts—have historically been considered the gold standard for bone grafting,^6,7 because they are osteoconductive, osteoinductive, and osteogenic. Autografting involves transplantation of bone from one anatomic site to another site in the same individual. Common harvest locations include the pelvic iliac crest, long bone intramedullary spaces (via reaming), and metaphyseal locations such as the distal femur and proximal tibia.^6,7 Cancellous autograft, cortical autograft, vascularized bone, bone marrow aspirate, and platelet-rich plasma all are examples of autografts.⁸ Autogenous bone is unique in that it has osteoconductive properties (bone mineral and collagen), osteoinductive properties (growth factors), and osteogenic properties (living osteogenic cells).^7,9

Bone allografts have been used for more than 100 years. These grafts are osteoconductive and to some degree osteoinductive. Allografts are processed in many ways. Most grafts are frozen in the form of morcellized cancellous bone, cortical struts, full diaphyseal segments, or osteoarticular grafts. The osteoarticular grafts are cryopreserved with glycerol or dimethyl sulfoxide to preserve some of the cartilage cells. Cancellous allografts are calcified collagenous space fillers with few, if any, living cells. Good results have been reported when using them for contained osseous defects.¹⁰ They function as an osteoconductive surface and contribute inductive proteins. Freezing is known to diminish immunogenicity of allogeneic tissue and allows the graft to be quarantined to screen for transmissible disease. Some bone tissue is freeze-dried and can be stored on the shelf at room temperature.

Allogeneic demineralized bone matrix (DBM) is a popular bone graft substitute. DBM is created through decalcification in acid to less than 3% residual, leaving only collagen and growth factors.¹¹ The collagen acts as a scaffold to allow for bone ingrowth, whereas growth factors such as BMPs contribute to the osteoinductivity of DBM. Typically, very few BMPs remain in these treated DBM products, and manufacturers will artificially add additional BMPs to the compound. DBM also has the advantage of decreased immunogenicity, because the cells in the allogeneic bone have been removed during its preparation.¹² The final product of DBM preparation is a powder that can be difficult to manage clinically.¹³ For this reason, several carriers have been developed to deliver DBM effectively to sites of bone defects. Carriers for DBM include low molecular carriers such as glycerol, calcium sulfate, and bioactive glass or polymer carriers such as collagen, carboxymethylcellulose, sodium alginate, and hyaluronic acid.^12,13 DBM products are also available in many forms, including sponges, strips, injectable putty, paste, and paste infused with chips.¹⁴ Several FDA-approved versions of DBM are available for commercial use, with moldable paste and/or putty being the most popular form for bone defects.^12,13 Another formulation of DBM is demineralized bone fibers, which are prepared from allograft demineralized into long fibers and which do not require carriers. Commercially available forms of demineralized bone fiber have largely been used as a graft alternative for spinal surgery.

Although DBM has been extensively investigated in preclinical studies,^15,16,17 few prospective or comparative studies have evaluated the efficacy of DBM in bone defects for patients with musculoskeletal tumors.^18,19 In addition, DBM is processed and distributed by tissue banks with no uniform method of production, leading to considerable variability with the osteoinductive potential of different DBM formulations. Several studies have reported on the variability in growth factors among commercially available DBMs.^20,21,22 This variability could result from the carrier chosen for the DBM as well as donor characteristics. Some tissue banks bioassay the DBM and supply only active forms.²³ The variability between different DBM formulations and the lack of studies evaluating long-term clinical effects of DBM make it difficult to properly characterize the efficacy of DBM in patients with musculoskeletal tumors. Furthermore, many of the growth factors added to available DBM products are contraindicated in tumor surgery.

Donor tissue is procured in an operating room environment before processing. The donor is screened for high-risk behavior or other disease exposures. The tissue is cultured and screened for bacteria, fungi, and virus contamination by blood serologies. The tissue is not released until all cultures and serologies are completed and negative. Overall, the risk of disease transmission from frozen or freeze-dried allograft is exceedingly low. Patients should nonetheless be informed of this risk. Surgeons should use only accredited tissue banks. As discussed in a 2022 article, the American Association of Tissue Banks and the FDA oversee accreditation.²⁴

Allografts can also be secondarily sterilized with gamma irradiation, which is effective for bacterial but
not viral contamination.²⁵ Irradiation, however, is known to weaken cortical allografts, particularly a concern with intercalary frozen allografts used for segmental defects in long bones, for which rigid internal fixation is critical. Intercalary allografts can be combined with vascularized autografts, such as a fibula autograft. Three-dimensional (3D)-printed cutting guides have gained interest to potentially help achieve the fit necessary for osteosynthesis. Allografts used to replace long bones with long-term follow-up have been shown to be associated with significant complications, including nonunion, fracture, infection, and cartilage degradation.^26,27,28

Osteoarticular allografts have been used to restore bones and joints in orthopaedic oncology for many years.²⁷ These grafts are frozen to diminish immunogenicity. Freezing causes crystal formation in the cartilage and kills chondrocytes. Cryopreservation methods have been developed to minimize cell death. Under the best of circumstances, only a small portion remains viable, and thus there is a significant likelihood of cartilage degradation with arthritis. This remains a major challenge with this type of bone and joint restoration. One way to address cartilage degradation is to create an allograft-prosthetic composite. As an example, a distal femoral allograft can be resurfaced with total knee arthroplasty. There have been some promising reports regarding this technique.²¹

Bioceramic bone graft substitutes are inorganic, often calcium-based, products with osteoconductive properties. They have a long record of clinical use dating back more than 100 years. Calcium-based bone graft substitutes provide the same mineral as bone. Calcium sulfate is an example of a ceramic that is either mined or manufactured. Its crystalline structure can be engineered to promote the rate of resorption and porosity. There is an inverse relationship between the strength of the bioceramic and its rate of resorption.⁹ As discussed in a 2021 study, porous materials resorb quicker, are much weaker, and are applicable only to a contained osseous defect, such as a unicameral bone cyst (UBC).²⁹ They are intended to dissolve over time and be replaced by host bone. Denser calcium phosphate ceramics are much stronger but can take years to resorb.³⁰ Numerous other calcium-based materials exist, including hydroxyapatite and combination products such as ceramic mixed with DBM. Ceramics offer unique properties of resorption and strength.