Use of allograft bone matrix in clinical orthopedics

Abstract

Clinical orthopedics continuously aims to improve methods for bone formation. Clinical applications where bone formation is necessary include critical long bone defects in orthopedic trauma or tumor patients. Though some biomaterials combined with autologous stem cells significantly improve bone repair, critical-size damages are still challenged with the suitable implantation of biomaterials and donor cell survival. Extracellular matrix (ECM) is the fundamental structure in tissues that can nest and nourish resident cells as well as support specific functions of the tissue type. ECM also plays a role in cell signaling to promote bone growth, healing and turnover. In the last decade, the use of bone-derived ECMs or ECM-similar biomaterials have been widely investigated, including decellularized and demineralized bone ECM. In this article, we reviewed the current productions and applications of decellularized and demineralized bone matrices. We also introduce the current study of whole limb decellularization and recellularization.

Article highlights

• The extracellular matrix (ECM) of bone has promoted bone growth, healing and turnover, and maintains its strength through the inorganic matrix.

• Demineralized bone matrix (DBM) is the allograft bone with only the organic compounds of ECM and decellularized bone matrix (dECM) is allograft or xenograft bone with removed nuclear material but maintenance of the native ECM components. Both are studied in clinical orthopedics.

Basic science of DBM

• Optimizing the amounts of collagen and hydroxyapatite in DBM can maximize hypoxia-inducible factor-1a (HIF-1a) mediated angiogenesis and stromal cell-derived factor-1a (SDF-1a) mediated recruitment of MSCs to sites of bone injury in bone healing.

• Cortical bone demineralization is completed by immersing the sample in acid and making bone matrix growth factors (BMP-2, BMP-7) bioavailable.

• Decellularization of bone involves physical, chemical and/or enzymatic techniques to strip bone of cellular components and leave behind noncellular ECM.

Clinical applications of DBM

• DBM has been successfully used in multiple spine surgeries, in the treatment of bone cysts, long bone nonunions and small foot bone defects.

• DBM has been studied in relation to tibial lengthening revealing enhanced consolidation.

Use of decellularized whole limbs

• The decellularization of entire limbs has been investigated as potential graft material.

• A proof-of-concept study has demonstrated the decellularization of an entire upper extremity of a human cadaver, including bone tissue.

Conclusion

• DBM is commonly used to treat recipient bone defects but is less mechanically stable due to the loss of hydroxyapatite.

• dECM retains the ECM structure and should be explored further in the future.

Future implications

• dECM should be used in human trials.

• Recellularization of decellularized entire limbs should be further explored in animal models.

Keywords: :

• allograft
• DBM
• decellularized and demineralized bone matrices
• extracellular matrix
• tissue repair

Acknowledgments

Preparation of this article is partially supported by the Western Michigan University Homer Stryker MD School of Medicine.

Author contributions

SM, Searched references, drafted and edited the manuscript. E Myrick, searched references, drafted and edited the manuscript. Created figures and tables. P Awad, searched references, drafted and edited the manuscript. Created figures and tables. V Hung, searched references, drafted and edited the manuscript. Created figures and tables.C Hinton, edited, drafted and involved resubmission. K Bovida, edited, discussed and proofread the final draft. K Kentera, edited, discussed and proofread the final draft. Y Li, supervised, structured, critically drafted and edited the manuscript. All authors approved the final version of the manuscript.

Financial disclosure

Preparation of this article is partially supported by the Western Michigan University Homer Stryker MD School of Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

Y Li is one of the executive editors for Journal of Cellular Biochemistry (JCB). All other authors declare no COI or otherwise. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.