Novel Periosteum-Mimetic Scaffolds for Coating Bone Allografts
Figure 1. Representative μCT 3D reconstructions showing a femur defect, proximal, and distal host tissue and bone callus (*) Longitudinal cross sections reveal graft incorporation at certain host‐graft junctions (#).
US Utility Patent Pending: US 2015/0086602 A1
Matt J Kipper
Nicole P Ehrhart
Timothy R Gonzalez
At A Glance
The inability of bone to heal large defects necessitates the use of bone grafts in many traumatic injuries and disease states. Bone autografts are considered the gold standard treatment due to their superior clinical performance attributed to the preservation of the periosteum. The periosteum is a critical component of bone healing due to its high vascularization, osteogenic progenitor cells, osteoinductive growth factors, and an osteoconductive structure. However, bone autografts are not without limitations, namely graft size availability and donor site morbidity that lead to further complications such as pain and infection.
Bone allografts have thus become a viable clinical alternative. However, to mitigate an immune response and disease transmission, bone allografts must undergo rigorous cleansing and sterilization steps before implantation, which includes removal of the periosteum. Devitalized allografts have a severely diminished osteogenic potential compared to live autografts. Cortical bone allografts experience limited remodeling due to their dense bone structure, which ultimately limits allografts’ osteointegration. This limited healing often results in premature failure; recent studies have documented segmental bone allografts having a 10-year failure rate as high as 60%. Clearly, strategies for improving the osteogenic and osteoinductive characteristics of bone allografts are needed.
Three distinct tissue engineered scaffolds have been developed in order to mimic the biological function of the periosteum:
(1) chitosan nanofibers were directly electrospun on murine bone allografts and subsequently modified with N,N,N-trimethyl chitosan and heparin polyelectrolyte multilayers using a layer-by-layer deposition technique;
(2) N,N,N-trimethyl chitosan and heparin polyelectrolyte multilayers were deposited on murine cortical bone coated with freeze-dried chitosan scaffold; and
(3) N,N,N-trimethyl chitosan and heparin polyelectrolyte multilayers were directly deposited onto murine cortical bone.
These three scaffolds can locally deliver growth factors and stem cells in order to improve host-allograft union. Furthermore, these methods can be expanded for other tissue engineering and regenerative medicine applications.
Figure 2 (Right) Scanning electron micrographs of:
Top Row (A) cortical bone, (B) cortical bone coated with PUA, and (C) cortical bone coated with PUA and a TMC-heparin PEM;
Middle Row (D) cortical bone coated with a chitosan freeze-dried (FD) scaffold, (E) the same FD scaffold after ammonium hydroxide neutralization, and (F) after TMC-heparin PEM deposition;
Bottom Row (G) cortical bone coated with electrospun chitosan nanofibers (NF), (H) the NF after ammonium hydroxide neutralization, and (I) after TMC-heparin PEM deposition
- Restore lost osteogenic and osteoinductive characteristics of devitalized bone allografts
- Scaffolds are directly deposited onto cortical bone
- Can deliver osteoprogenitor cells
- Durable and cytocompatible
- Improved bone graft integration
- Restoration of lost osteogenic and osteoinductive characteristics of devitalized bone allografts
- Regenerative bone applications
- Tissue Engineering
Martins, Alessandro F., et al. “Chitosan/Iota-Carrageenan and Chitosan/Pectin Polyelectrolyte Multilayer Scaffolds with Antiadhesive and Bactericidal Properties.” Applied Surface Science, North-Holland, 16 Oct. 2019, www.sciencedirect.com/science/article/abs/pii/S0169433219330983?via%3Dihub.
Romero R, Travers JK, Asbury E, Pennybaker A, Chubb L, Rose R, Ehrhart NP, Kipper MJ. Combined delivery of FGF-2, TGF-β1, and adipose-derived stem cells from an engineered periosteum to a critical-sized mouse femur defect. J Biomed Mater Res A. 2017 Mar;105(3):900-911. doi: 10.1002/jbm.a.35965. Epub 2016 Dec 23. PMID: 27874253.
Romero, Raimundo, et al. “Coating Cortical Bone Allografts with Periosteum-Mimetic Scaffolds Made of Chitosan, Trimethyl Chitosan, and Heparin.” Carbohydrate Polymers, Elsevier, 14 Jan. 2015, www.sciencedirect.com/science/article/abs/pii/S0144861715000259.
Last updated: February 2021