Bone xenotransplantation: A review of the history, orthopedic clinical literature, and a single‐center case series

Abstract

Background: One-half of all orthopedic surgeries require bone grafting for successful outcomes in fusions, reconstructive procedures, and the treatment of osseous defects resulting from trauma, tumor, infection, or congenital deformity. Autologous bone grafts are taken from the patient's own body and remain the "gold standard" graft choice but are limited in supply and impart significant patient morbidity. Xenograft bone is an attractive alternative from donors with controlled biology, in large supply and at a theoretically lower cost. Clinical results with xenograft bone for orthopedic applications have been mixed in the limited clinical trials published. Methods: In the current review, we introduce fundamental principles of bone grafting, systematically review all orthopedic clinical studies reporting outcomes on patients transplanted with xenograft bone, and we present our own clinical results from patients grafted with bovine bone in foot and ankle reconstructive procedures. Results: Thirty-one clinical studies were identified for review and the majority (47%) were from spine surgery literature. Favorable results were reported in 44% of studies while 47% of studies reported poor outcomes and discouraged use of xenograft bone products. In our own clinical series, xenograft failed to integrate with host bone in 58% of cases and persistent pain was reported in 83% of cases. Conclusions: This is the first systematic review of clinical results reported after bone xenotransplantation for orthopaedic surgery applications. Current literature does not support the use of xenograft bone products and our institution's results are consistent with this conclusion. Our laboratory has reported promising pre-clinical results with a xenograft product derived from porcine cancellous bone, but additional testing is required before considering clinical translation.

Innovative Concepts and Recent Breakthrough for Engineered Graft and Constructs for Bone Regeneration: A Literature Systematic Review

“…A recent review on the use of bovine bone highlighted in the conclusions that 58% of cases failed in osseointegration, while 83% of these continued to have pain even after a long time. The main factor causing this complication is the body’s immune response to this material [ 165 ]. Therefore, for xenografts, the main antigen is the epitop alpha Gal, and to inhibit this antigen, the xenograft should be decellularized, and only then can it be used as a scaffold.…”

“…Therefore, for xenografts, the main antigen is the epitop alpha Gal, and to inhibit this antigen, the xenograft should be decellularized, and only then can it be used as a scaffold. However, the risk of an antigenic reaction will always be there, especially for bovine bone [ 165 ]. A new combination of bovine bone with type 1 atelocollagen has been recommended to minimize the antigenic reaction.…”

Xenotransplantation literature update for September – October 2020

“…It is essential for the grafted bone to be biocompatible, osteoconductive, osteogenic, osteoinductive with no risk of disease transmission and not elicit a host response 14 . Bracey et al 15 review the history of bone transplantation discussing the multiple advantages of autografts, allografts, and xenografts, as well as several complications. Allografts retrieved from living or deceased human donors provide osteoconductivity but is limited by osteoinduction after sterilization due to inactive surface proteins.…”

“…Xenografts on the other hand are abundant from healthy donors and are available at a lower cost 17 . Xenograft‐derived bone products are currently not FDA approved due to poor outcomes 15 . Porcine‐derived bone grafts could replace existing bovine‐derived grafts due to species similarity 18‐22 .…”

The construction of a novel xenograft bovine bone scaffold, (DSS)6-liposome/CKIP-1 siRNA/calcine bone and its osteogenesis evaluation on skull defect in rats

“…It is rich in sources and the tissue, cell, blood compatibility and biological safety are also good. However, when it was implanted into organisms alone, it was difficult to become an ideal bone biological scaffold due to its limited surface area and lack of active factors [ 1 , 2 ]. The composite material can complement each other in terms of their properties.…”