Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation

Overview

Journal J Funct Biomater

Specialty Biomedical Engineering

Date 2024 Jun 26

PMID 38921519

Authors

Jolene Quek

Catarina Vizetto-Duarte

Swee Hin Teoh

Yen Choo

Affiliations

Soon will be listed here.

Abstract

The management and reconstruction of critical-sized segmental bone defects remain a major clinical challenge for orthopaedic clinicians and surgeons. In particular, regenerative medicine approaches that involve incorporating stem cells within tissue engineering scaffolds have great promise for fracture management. This narrative review focuses on the primary components of bone tissue engineering-stem cells, scaffolds, the microenvironment, and vascularisation-addressing current advances and translational and regulatory challenges in the current landscape of stem cell therapy for critical-sized bone defects. To comprehensively explore this research area and offer insights for future treatment options in orthopaedic surgery, we have examined the latest developments and advancements in bone tissue engineering, focusing on those of clinical relevance in recent years. Finally, we present a forward-looking perspective on using stem cells in bone tissue engineering for critical-sized segmental bone defects.

Citing Articles

Application of gelatin-based composites in bone tissue engineering.

Wu E, Huang L, Shen Y, Wei Z, Li Y, Wang J Heliyon. 2024; 10(16):e36258.

PMID: 39224337 PMC: 11367464. DOI: 10.1016/j.heliyon.2024.e36258.

References

Chan B, Leong K . Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J. 2008; 17 Suppl 4:467-79. PMC: 2587658. DOI: 10.1007/s00586-008-0745-3. View

Wojtowicz A, Shekaran A, Oest M, Dupont K, Templeman K, Hutmacher D . Coating of biomaterial scaffolds with the collagen-mimetic peptide GFOGER for bone defect repair. Biomaterials. 2010; 31(9):2574-82. PMC: 2813962. DOI: 10.1016/j.biomaterials.2009.12.008. View

Li Y, Meng H, Liu Y, Lee B . Fibrin gel as an injectable biodegradable scaffold and cell carrier for tissue engineering. ScientificWorldJournal. 2015; 2015:685690. PMC: 4380102. DOI: 10.1155/2015/685690. View

Unagolla J, Jayasuriya A . Hydrogel-based 3D bioprinting: A comprehensive review on cell-laden hydrogels, bioink formulations, and future perspectives. Appl Mater Today. 2020; 18. PMC: 7414424. DOI: 10.1016/j.apmt.2019.100479. View

Shu X, Ghosh K, Liu Y, Palumbo F, Luo Y, Clark R . Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel. J Biomed Mater Res A. 2004; 68(2):365-75. DOI: 10.1002/jbm.a.20002. View

Kwon S, Kwon Y, Lee T, Park G, Kim J . Recent advances in stem cell therapeutics and tissue engineering strategies. Biomater Res. 2019; 22:36. PMC: 6299977. DOI: 10.1186/s40824-018-0148-4. View

Unal A, West J . Synthetic ECM: Bioactive Synthetic Hydrogels for 3D Tissue Engineering. Bioconjug Chem. 2020; 31(10):2253-2271. DOI: 10.1021/acs.bioconjchem.0c00270. View

Guiotto M, Raffoul W, Hart A, Riehle M, di Summa P . Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review. J Transl Med. 2020; 18(1):351. PMC: 7493356. DOI: 10.1186/s12967-020-02489-4. View

Wong C, Inman E, Spaethe R, Helgerson S . Fibrin-based biomaterials to deliver human growth factors. Thromb Haemost. 2003; 89(3):573-82. View

10.

Birru B, Mekala N, Parcha S . Improved osteogenic differentiation of umbilical cord blood MSCs using custom made perfusion bioreactor. Biomed J. 2018; 41(5):290-297. PMC: 6306301. DOI: 10.1016/j.bj.2018.07.002. View

11.

Stamnitz S, Klimczak A . Mesenchymal Stem Cells, Bioactive Factors, and Scaffolds in Bone Repair: From Research Perspectives to Clinical Practice. Cells. 2021; 10(8). PMC: 8392210. DOI: 10.3390/cells10081925. View

12.

Cui H, Zhu W, Nowicki M, Zhou X, Khademhosseini A, Zhang L . Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design. Adv Healthc Mater. 2016; 5(17):2174-81. PMC: 5014673. DOI: 10.1002/adhm.201600505. View

13.

Volarevic V, Markovic B, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N . Ethical and Safety Issues of Stem Cell-Based Therapy. Int J Med Sci. 2018; 15(1):36-45. PMC: 5765738. DOI: 10.7150/ijms.21666. View

14.

Chen J, Deng L, Porter C, Alexander G, Patel D, Vines J . Angiogenic and Osteogenic Synergy of Human Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells Cocultured on a Nanomatrix. Sci Rep. 2018; 8(1):15749. PMC: 6200728. DOI: 10.1038/s41598-018-34033-2. View

15.

Ressler A . Chitosan-Based Biomaterials for Bone Tissue Engineering Applications: A Short Review. Polymers (Basel). 2022; 14(16). PMC: 9416295. DOI: 10.3390/polym14163430. View

16.

Garcia J, Clark A, Garcia A . Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects. J Biomed Mater Res A. 2015; 104(4):889-900. PMC: 5106804. DOI: 10.1002/jbm.a.35626. View

17.

Wu M, Han Z, Liu J, Wang Y, Zhang J, Li C . Serum-free media and the immunoregulatory properties of mesenchymal stem cells in vivo and in vitro. Cell Physiol Biochem. 2014; 33(3):569-80. DOI: 10.1159/000358635. View

18.

Poldervaart M, Goversen B, de Ruijter M, Abbadessa A, Melchels F, Oner F . 3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity. PLoS One. 2017; 12(6):e0177628. PMC: 5460858. DOI: 10.1371/journal.pone.0177628. View

19.

Mercado-Pagan A, Stahl A, Shanjani Y, Yang Y . Vascularization in bone tissue engineering constructs. Ann Biomed Eng. 2015; 43(3):718-29. PMC: 4979539. DOI: 10.1007/s10439-015-1253-3. View

20.

Grassel S, Lorenz J . Tissue-engineering strategies to repair chondral and osteochondral tissue in osteoarthritis: use of mesenchymal stem cells. Curr Rheumatol Rep. 2014; 16(10):452. PMC: 4182613. DOI: 10.1007/s11926-014-0452-5. View