Hierarchy Reproduction: Multiphasic Strategies for Tendon/Ligament-Bone Junction Repair

Overview

Journal Biomater Res

Date 2025 Jan 23

PMID 39844867

Authors

Kaiting Chen

Zezheng Liu

Xinying Zhou

Wanyu Zheng

He Cao

Zijian Yang

Zhengao Wang

Chengyun Ning

Qingchu Li

Huiyu Zhao

Affiliations

Soon will be listed here.

Abstract

Tendon/ligament-bone junctions (T/LBJs) are susceptible to damage during exercise, resulting in anterior cruciate ligament rupture or rotator cuff tear; however, their intricate hierarchical structure hinders self-regeneration. Multiphasic strategies have been explored to fuel heterogeneous tissue regeneration and integration. This review summarizes current multiphasic approaches for rejuvenating functional gradients in T/LBJ healing. Synthetic, natural, and organism-derived materials are available for in vivo validation. Both discrete and gradient layouts serve as sources of inspiration for organizing specific cues, based on the theories of biomaterial topology, biochemistry, mechanobiology, and in situ delivery therapy, which form interconnected network within the design. Novel engineering can be constructed by electrospinning, 3-dimensional printing, bioprinting, textiling, and other techniques. Despite these efforts being limited at present stage, multiphasic scaffolds show great potential for precise reproduction of native T/LBJs and offer promising solutions for clinical dilemmas.

References

Yin Z, Chen X, Chen J, Shen W, Hieu Nguyen T, Gao L . The regulation of tendon stem cell differentiation by the alignment of nanofibers. Biomaterials. 2009; 31(8):2163-75. DOI: 10.1016/j.biomaterials.2009.11.083. View

Jiang N, He J, Zhang W, Li D, Lv Y . Directed differentiation of BMSCs on structural/compositional gradient nanofibrous scaffolds for ligament-bone osteointegration. Mater Sci Eng C Mater Biol Appl. 2020; 110:110711. DOI: 10.1016/j.msec.2020.110711. View

Micalizzi S, Russo L, Giacomelli C, Montemurro F, De Maria C, Nencioni M . Multimaterial and multiscale scaffold for engineering enthesis organ. Int J Bioprint. 2023; 9(5):763. PMC: 10339436. DOI: 10.18063/ijb.763. View

Li C, Ouyang L, Armstrong J, Stevens M . Advances in the Fabrication of Biomaterials for Gradient Tissue Engineering. Trends Biotechnol. 2020; 39(2):150-164. DOI: 10.1016/j.tibtech.2020.06.005. View

Lipner J, Liu W, Liu Y, Boyle J, Genin G, Xia Y . The mechanics of PLGA nanofiber scaffolds with biomimetic gradients in mineral for tendon-to-bone repair. J Mech Behav Biomed Mater. 2014; 40:59-68. PMC: 4428326. DOI: 10.1016/j.jmbbm.2014.08.002. View

Chen R, Pye J, Li J, Little C, Li J . Multiphasic scaffolds for the repair of osteochondral defects: Outcomes of preclinical studies. Bioact Mater. 2023; 27:505-545. PMC: 10173014. DOI: 10.1016/j.bioactmat.2023.04.016. View

Yun H, Jin Y, Shin D, Noh S, Kim K, Park J . Fibrocartilage extracellular matrix augmented demineralized bone matrix graft repairs tendon-to-bone interface in a rabbit tendon reconstruction model. Biomater Adv. 2023; 152:213522. DOI: 10.1016/j.bioadv.2023.213522. View

Gogele C, Hahn J, Schulze-Tanzil G . Anatomical Tissue Engineering of the Anterior Cruciate Ligament Entheses. Int J Mol Sci. 2023; 24(11). PMC: 10253789. DOI: 10.3390/ijms24119745. View

Chang R, Shanley J, Kersh M, Harley B . Tough and tunable scaffold-hydrogel composite biomaterial for soft-to-hard musculoskeletal tissue interfaces. Sci Adv. 2020; 6(34):eabb6763. PMC: 7438087. DOI: 10.1126/sciadv.abb6763. View

10.

Zhang B, Huang J, Narayan R . Gradient scaffolds for osteochondral tissue engineering and regeneration. J Mater Chem B. 2020; 8(36):8149-8170. DOI: 10.1039/d0tb00688b. View

11.

Novakova S, Mahalingam V, Florida S, Mendias C, Allen A, Arruda E . Tissue-engineered tendon constructs for rotator cuff repair in sheep. J Orthop Res. 2017; 36(1):289-299. DOI: 10.1002/jor.23642. View

12.

Gao H, Wang L, Lin Z, Jin H, Lyu Y, Kang Y . Bi-lineage inducible and immunoregulatory electrospun fibers scaffolds for synchronous regeneration of tendon-to-bone interface. Mater Today Bio. 2023; 22:100749. PMC: 10400930. DOI: 10.1016/j.mtbio.2023.100749. View

13.

Ahn T, Gidley D, Thornton A, Wong-Foy A, Orr B, Kozloff K . Hierarchical Nature of Nanoscale Porosity in Bone Revealed by Positron Annihilation Lifetime Spectroscopy. ACS Nano. 2021; 15(3):4321-4334. PMC: 8176962. DOI: 10.1021/acsnano.0c07478. View

14.

Diloksumpan P, de Ruijter M, Castilho M, Gbureck U, Vermonden T, van Weeren P . Combining multi-scale 3D printing technologies to engineer reinforced hydrogel-ceramic interfaces. Biofabrication. 2020; 12(2):025014. PMC: 7116207. DOI: 10.1088/1758-5090/ab69d9. View

15.

Khalak F, Garcia-Villen F, Ruiz-Alonso S, Pedraz J, Saenz-Del-Burgo L . Decellularized Extracellular Matrix-Based Bioinks for Tendon Regeneration in Three-Dimensional Bioprinting. Int J Mol Sci. 2022; 23(21). PMC: 9657326. DOI: 10.3390/ijms232112930. View

16.

Guan Z, Wu C, Wu J, Tai C, Yu J, Chen H . Multifunctional and Continuous Gradients of Biointerfaces Based on Dual Reverse Click Reactions. ACS Appl Mater Interfaces. 2016; 8(22):13812-8. DOI: 10.1021/acsami.6b03908. View

17.

Bedi A, Fox A, Kovacevic D, Deng X, Warren R, Rodeo S . Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair. Am J Sports Med. 2009; 38(2):308-17. DOI: 10.1177/0363546509347366. View

18.

Li X, Liu B, Pei B, Chen J, Zhou D, Peng J . Inkjet Bioprinting of Biomaterials. Chem Rev. 2020; 120(19):10793-10833. DOI: 10.1021/acs.chemrev.0c00008. View

19.

Lee H, Rho J, Messersmith P . Facile Conjugation of Biomolecules onto Surfaces via Mussel Adhesive Protein Inspired Coatings. Adv Mater. 2009; 21(4):431-434. PMC: 2755254. DOI: 10.1002/adma.200801222. View

20.

Cheng P, Han P, Zhao C, Zhang S, Wu H, Ni J . High-purity magnesium interference screws promote fibrocartilaginous entheses regeneration in the anterior cruciate ligament reconstruction rabbit model via accumulation of BMP-2 and VEGF. Biomaterials. 2015; 81:14-26. DOI: 10.1016/j.biomaterials.2015.12.005. View