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Bone Grafting in the Regenerative Reconstruction of Critical-Size Long Bone Segmental Defects

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Bone Tissue Engineering

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Abstract

Regenerative reconstruction of critical-size long bone segmental defects (LBSD) arising from high-energy traumas or tumor resections presents a formidable clinical challenge and imposes tremendous burdens to the healthcare systems worldwide. Standard treatment modalities like autologous cancellous bone grafting and allogenic cortical bone grafting are inadequate for LBSD due to limited supplies and suboptimal in vivo resorption of the former and poor fixation/tissue integration of the latter, respectively. These limitations have inspired the design of new synthetic bone grafts that integrate osteoinductivity and osteoconductivity with desired handling characteristics and controlled biodegradability. This chapter first outlines periosteal surface engineering strategies aimed at improving the in vivo performance of structural allografts, then reviews recent advances in synthetic bone grafts composed of demineralized bone matrices, titanium mesh cages, bioceramics, natural polymers, or synthetic polymers and composites. The discussions are centered around their applications for the regenerative repair of critical-size LBSD, contrasting their functional regeneration outcomes (e.g. restoration of mechanical integrity, quantification of new bone formation), whenever possible, with those achieved by clinical standards or to health controls.

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Abbreviations

3D printing:

Three-dimensional printing

ACS:

Absorbable collagen sponge

ADSC:

Adipose-derived stem cell

BMP:

Bone morphogenetic protein

BMSC:

Bone marrow-derived stromal cell

CAD:

Computer-assisted design

CaP:

Calcium phosphate

CT:

Computer tomography

DBM:

Demineralized bone matrix

ECM:

Extracellular matrix

FDA:

Food and Drug Administration

FGF23:

Fibroblast growth factor 23

HA:

Hyaluronic acid

hAFSC:

Human amniotic fluid-derived stem cell

HAp:

Hydroxyapatite

HDB:

Heterogeneous deproteinized bone

Ihh:

Indian hedgehog

LBSD:

Long bone segmental defect

MSC:

Mesenchymal stem cell

mSSC:

Mouse skeletal stem cell

OVX:

Ovariectomy

PCL:

Polycaprolactone

PEG:

Poly(ethylene glycol)

PEGDA:

Poly(ethylene glycol) diacrylate

PELGA:

Poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid)

PGA:

Poly(glycolic acid)

PLGA:

Poly(lactic-co-glycolic acid)

PLA:

Poly(lactic acid)

PLA-DX-PEG:

Poly d,l-lactic acid-p-dioxanone-polyethylene glycol block copolymer

PVA:

Poly(vinyl alcohol)

rAAV:

Recombinant adeno-associated virus

RANKL:

Receptor activator of nuclear factor κB ligand

rhBMP-2:

Recombinant human bone morphogenetic protein-2

rhBMP-2/7:

Recombinant human bone morphogenetic protein-2/7 heterodimer

rt:

Room temperature

TCP:

Tricalcium phosphate

TEP:

Tissue-engineered periosteum

VEGF:

Vascular endothelial growth factor

WSF:

Wistar skin fibroblast

β-TCP:

β-Tricalcium phosphate

μ-CT:

Micro-computed tomography

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Acknowledgements

This work is supported by an Alex Lemonade Stand Foundation Innovation Grant and a BRIDGE Award from the University of Massachusetts Medical School.

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The authors declare there is no conflict of interests.

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Authors and Affiliations

  1. Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, MA, USA

    **aowen Xu & Jie Song

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  1. **aowen Xu
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  2. Jie Song
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Correspondence to Jie Song .

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    Fernando P.S. Guastaldi

  2. College Park, MD, USA

    Bhushan Mahadik

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Xu, X., Song, J. (2022). Bone Grafting in the Regenerative Reconstruction of Critical-Size Long Bone Segmental Defects. In: Guastaldi, F.P., Mahadik, B. (eds) Bone Tissue Engineering. Springer, Cham. https://doi.org/10.1007/978-3-030-92014-2_8

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