Bone Regenerative Effect of Injectable Hypoxia Preconditioned Serum-Fibrin (HPS-F) in an Ex Vivo Bone Defect Model

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 May 25

PMID 38791352

Authors

Jun Jiang

Lynn Roper

Finja Fuchs

Marc Hanschen

Sandra Failer

Sarah Alageel

Xiaobin Cong

Ulf Dornseifer

Arndt F Schilling

Hans-Gunther Machens

Philipp Moog

Affiliations

Soon will be listed here.

Abstract

Biofunctionalized hydrogels are widely used in tissue engineering for bone repair. This study examines the bone regenerative effect of the blood-derived growth factor preparation of Hypoxia Preconditioned Serum (HPS) and its fibrin-hydrogel formulation (HPS-F) on drilled defects in embryonic day 19 chick femurs. Measurements of bone-related growth factors in HPS reveal significant elevations of Osteopontin, Osteoprotegerin, and soluble-RANKL compared with normal serum (NS) but no detection of BMP-2/7 or Osteocalcin. Growth factor releases from HPS-F are measurable for at least 7 days. Culturing drilled femurs organotypically on a liquid/gas interface with HPS media supplementation for 10 days demonstrates a 34.6% increase in bone volume and a 52.02% increase in bone mineral density (BMD) within the defect area, which are significantly higher than NS and a basal-media-control, as determined by microcomputed tomography. HPS-F-injected femur defects implanted on a chorioallantoic membrane (CAM) for 7 days exhibit an increase in bone mass of 123.5% and an increase in BMD of 215.2%, which are significantly higher than normal-serum-fibrin (NS-F) and no treatment. Histology reveals calcification, proteoglycan, and collagen fiber deposition in the defect area of HPS-F-treated femurs. Therefore, HPS-F may offer a promising and accessible therapeutic approach to accelerating bone regeneration by a single injection into the bone defect site.

Citing Articles

Relationship of Chronic Stress and Hypertension with Bone Resorption.

Paulini M, Aimone M, Feldman S, Buchaim D, Buchaim R, Issa J J Funct Morphol Kinesiol. 2025; 10(1.

PMID: 39846662 PMC: 11755563. DOI: 10.3390/jfmk10010021.

Hypoxia Preconditioned Serum Hydrogel (HPS-H) Accelerates Dermal Regeneration in a Porcine Wound Model.

Jiang J, Man T, Kirsch M, Knoedler S, Andersen K, Reiser J Gels. 2024; 10(11).

PMID: 39590104 PMC: 11593443. DOI: 10.3390/gels10110748.

References

Moog P, Schams R, Schneidinger A, Schilling A, Machens H, Hadjipanayi E . Effect of Hypoxia Preconditioned Secretomes on Lymphangiogenic and Angiogenic Sprouting: An in Vitro Analysis. Biomedicines. 2020; 8(9). PMC: 7555444. DOI: 10.3390/biomedicines8090365. View

Inglis S, Schneider K, Kanczler J, Redl H, Oreffo R . Harnessing Human Decellularized Blood Vessel Matrices and Cellular Construct Implants to Promote Bone Healing in an Ex Vivo Organotypic Bone Defect Model. Adv Healthc Mater. 2018; 8(9):e1800088. DOI: 10.1002/adhm.201800088. View

Zhang L, Bi Q, Zhao C, Chen J, Cai M, Chen X . Recent Advances in Biomaterials for the Treatment of Bone Defects. Organogenesis. 2020; 16(4):113-125. PMC: 7714479. DOI: 10.1080/15476278.2020.1808428. View

Anderson J, Rodriguez A, Chang D . Foreign body reaction to biomaterials. Semin Immunol. 2007; 20(2):86-100. PMC: 2327202. DOI: 10.1016/j.smim.2007.11.004. View

Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M . Coupling of bone resorption and formation by RANKL reverse signalling. Nature. 2018; 561(7722):195-200. DOI: 10.1038/s41586-018-0482-7. View

Moog P, Kirchhoff K, Bekeran S, Bauer A, von Isenburg S, Dornseifer U . Comparative Evaluation of the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes and Platelet-Rich Plasma: An In Vitro Analysis. Biomedicines. 2020; 8(1). PMC: 7168246. DOI: 10.3390/biomedicines8010016. View

Sheikh Z, Najeeb S, Khurshid Z, Verma V, Rashid H, Glogauer M . Biodegradable Materials for Bone Repair and Tissue Engineering Applications. Materials (Basel). 2017; 8(9):5744-5794. PMC: 5512653. DOI: 10.3390/ma8095273. View

Kushchayeva Y, Pestun I, Kushchayev S, Radzikhovska N, Lewiecki E . Advancement in the Treatment of Osteoporosis and the Effects on Bone Healing. J Clin Med. 2022; 11(24). PMC: 9781093. DOI: 10.3390/jcm11247477. View

Safari B, Davaran S, Aghanejad A . Osteogenic potential of the growth factors and bioactive molecules in bone regeneration. Int J Biol Macromol. 2021; 175:544-557. DOI: 10.1016/j.ijbiomac.2021.02.052. View

10.

Jiang J, Altammar J, Cong X, Ramsauer L, Steinbacher V, Dornseifer U . Hypoxia Preconditioned Serum (HPS) Promotes Proliferation and Chondrogenic Phenotype of Chondrocytes In Vitro. Int J Mol Sci. 2023; 24(13). PMC: 10341616. DOI: 10.3390/ijms241310441. View

11.

Mazini L, Rochette L, Amine M, Malka G . Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). Int J Mol Sci. 2019; 20(10). PMC: 6566837. DOI: 10.3390/ijms20102523. View

12.

Elango J, Bao B, Wu W . The hidden secrets of soluble RANKL in bone biology. Cytokine. 2021; 144:155559. DOI: 10.1016/j.cyto.2021.155559. View

13.

Moog P, Jensch M, Hughes J, Salgin B, Dornseifer U, Machens H . Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes. Biomedicines. 2020; 8(8). PMC: 7459715. DOI: 10.3390/biomedicines8080283. View

14.

Nikolova M, Chavali M . Recent advances in biomaterials for 3D scaffolds: A review. Bioact Mater. 2019; 4:271-292. PMC: 6829098. DOI: 10.1016/j.bioactmat.2019.10.005. View

15.

Kobayashi E, Fluckiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B . Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig. 2016; 20(9):2353-2360. DOI: 10.1007/s00784-016-1719-1. View

16.

Steijvers E, Ghei A, Xia Z . Manufacturing artificial bone allografts: a perspective. Biomater Transl. 2022; 3(1):65-80. PMC: 9255790. DOI: 10.12336/biomatertransl.2022.01.007. View

17.

Hadjipanayi E, Kuhn P, Moog P, Bauer A, Kuekrek H, Mirzoyan L . The Fibrin Matrix Regulates Angiogenic Responses within the Hemostatic Microenvironment through Biochemical Control. PLoS One. 2015; 10(8):e0135618. PMC: 4552838. DOI: 10.1371/journal.pone.0135618. View

18.

Hadjipanayi E, BROWN R, Mudera V, Deng D, Liu W, Cheema U . Controlling physiological angiogenesis by hypoxia-induced signaling. J Control Release. 2010; 146(3):309-17. DOI: 10.1016/j.jconrel.2010.05.037. View

19.

Moog P, Hughes J, Jiang J, Roper L, Dornseifer U, Schilling A . Comparison of the Effect of Different Conditioning Media on the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes: Towards Engineering Next-Generation Autologous Growth Factor Cocktails. Int J Mol Sci. 2023; 24(6). PMC: 10049474. DOI: 10.3390/ijms24065485. View

20.

Farshidfar N, Amiri M, Jafarpour D, Hamedani S, Niknezhad S, Tayebi L . The feasibility of injectable PRF (I-PRF) for bone tissue engineering and its application in oral and maxillofacial reconstruction: From bench to chairside. Biomater Adv. 2022; 134:112557. PMC: 9295636. DOI: 10.1016/j.msec.2021.112557. View