Strategies for Controlled Delivery of Growth Factors and Cells for Bone Regeneration

Overview

Journal Adv Drug Deliv Rev

Specialty Pharmacology

Date 2012 Feb 21

PMID 22342771

Citations 205

Authors

Tiffany N Vo

F Kurtis Kasper

Antonios G Mikos

Affiliations

Soon will be listed here.

Abstract

The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with pre-programmed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering.

Citing Articles

Biofunctionalization of Collagen Barrier Membranes with Bone-Conditioned Medium, as a Natural Source of Growth Factors, Enhances Osteoblastic Cell Behavior.

Ashoka Sreeja H, Couso-Queiruga E, Raabe C, Chappuis V, Asparuhova M Int J Mol Sci. 2025; 26(4).

PMID: 40004074 PMC: 11855076. DOI: 10.3390/ijms26041610.

The Role of Hyaluronic Acid in Alveolar Ridge Preservation: A Systematic Review of Its Biological and Regenerative Potential According to PRISMA Guidelines and the Cochrane Handbook.

Ronsivalle V, Santonocito S, Giudice R, Bocchieri S, Didomenico S, Cicciu M Biomedicines. 2025; 13(2).

PMID: 40002864 PMC: 11853319. DOI: 10.3390/biomedicines13020451.

Dual release scaffolds as a promising strategy for enhancing bone regeneration: an updated review.

Zhang Y, Zhou C, Xie Q, Xia L, Liu L, Bao W Nanomedicine (Lond). 2025; 20(4):371-388.

PMID: 39891431 PMC: 11812394. DOI: 10.1080/17435889.2025.2457317.

Advancements in Bone Replacement Techniques-Potential Uses After Maxillary and Mandibular Resections Due to Medication-Related Osteonecrosis of the Jaw (MRONJ).

Bovari-Biri J, Miskei J, Kover Z, Steinerbrunner-Nagy A, Kardos K, Maroti P Cells. 2025; 14(2).

PMID: 39851573 PMC: 11763601. DOI: 10.3390/cells14020145.

Electrospinning based biomaterials for biomimetic fabrication, bioactive protein delivery and wound regenerative repair.

Dai X, Nie W, Shen H, Machens H, Boker K, Taheri S Regen Biomater. 2025; 12:rbae139.

PMID: 39803356 PMC: 11723536. DOI: 10.1093/rb/rbae139.

References

Shin H, Ruhe P, Mikos A, Jansen J . In vivo bone and soft tissue response to injectable, biodegradable oligo(poly(ethylene glycol) fumarate) hydrogels. Biomaterials. 2003; 24(19):3201-11. DOI: 10.1016/s0142-9612(03)00168-6. View

Puleo D, Kissling R, Sheu M . A technique to immobilize bioactive proteins, including bone morphogenetic protein-4 (BMP-4), on titanium alloy. Biomaterials. 2002; 23(9):2079-87. DOI: 10.1016/s0142-9612(01)00339-8. View

Liao J, Guo X, Nelson D, Kasper F, Mikos A . Modulation of osteogenic properties of biodegradable polymer/extracellular matrix scaffolds generated with a flow perfusion bioreactor. Acta Biomater. 2010; 6(7):2386-93. PMC: 2874124. DOI: 10.1016/j.actbio.2010.01.011. View

Oest M, Dupont K, Kong H, Mooney D, Guldberg R . Quantitative assessment of scaffold and growth factor-mediated repair of critically sized bone defects. J Orthop Res. 2007; 25(7):941-50. DOI: 10.1002/jor.20372. View

Haidar Z, Tabrizian M, Hamdy R . A hybrid rhOP-1 delivery system enhances new bone regeneration and consolidation in a rabbit model of distraction osteogenesis. Growth Factors. 2009; 28(1):44-55. DOI: 10.3109/08977190903367788. View

Rundle C, Strong D, Chen S, Linkhart T, Sheng M, Wergedal J . Retroviral-based gene therapy with cyclooxygenase-2 promotes the union of bony callus tissues and accelerates fracture healing in the rat. J Gene Med. 2007; 10(3):229-41. DOI: 10.1002/jgm.1148. View

Santos M, Unger R, Sousa R, Reis R, Kirkpatrick C . Crosstalk between osteoblasts and endothelial cells co-cultured on a polycaprolactone-starch scaffold and the in vitro development of vascularization. Biomaterials. 2009; 30(26):4407-15. DOI: 10.1016/j.biomaterials.2009.05.004. View

Kirker-Head C . Potential applications and delivery strategies for bone morphogenetic proteins. Adv Drug Deliv Rev. 2000; 43(1):65-92. DOI: 10.1016/s0169-409x(00)00078-8. View

Geiger M, Li R, Friess W . Collagen sponges for bone regeneration with rhBMP-2. Adv Drug Deliv Rev. 2003; 55(12):1613-29. DOI: 10.1016/j.addr.2003.08.010. View

10.

Grellier M, Granja P, Fricain J, Bidarra S, Renard M, Bareille R . The effect of the co-immobilization of human osteoprogenitors and endothelial cells within alginate microspheres on mineralization in a bone defect. Biomaterials. 2009; 30(19):3271-8. DOI: 10.1016/j.biomaterials.2009.02.033. View

11.

Pham Q, Kasper F, Mistry A, Sharma U, Yasko A, Jansen J . Analysis of the osteoinductive capacity and angiogenicity of an in vitro generated extracellular matrix. J Biomed Mater Res A. 2008; 88(2):295-303. DOI: 10.1002/jbm.a.31875. View

12.

Kang S, Kong B, Oh E, Choi J, Choi I . Osteoconductive conjugation of bone morphogenetic protein-2 onto titanium/titanium oxide surfaces coated with non-biofouling poly(poly(ethylene glycol) methacrylate). Colloids Surf B Biointerfaces. 2009; 75(1):385-9. DOI: 10.1016/j.colsurfb.2009.08.039. View

13.

Yang C, Frei H, Rossi F, Burt H . The differential in vitro and in vivo responses of bone marrow stromal cells on novel porous gelatin-alginate scaffolds. J Tissue Eng Regen Med. 2009; 3(8):601-14. DOI: 10.1002/term.201. View

14.

Felix Lanao R, Leeuwenburgh S, Wolke J, Jansen J . In vitro degradation rate of apatitic calcium phosphate cement with incorporated PLGA microspheres. Acta Biomater. 2011; 7(9):3459-68. DOI: 10.1016/j.actbio.2011.05.036. View

15.

Lin Z, Duan Z, Guo X, Li J, Lu H, Zheng Q . Bone induction by biomimetic PLGA-(PEG-ASP)n copolymer loaded with a novel synthetic BMP-2-related peptide in vitro and in vivo. J Control Release. 2010; 144(2):190-5. DOI: 10.1016/j.jconrel.2010.02.016. View

16.

Neer R, Arnaud C, Zanchetta J, Prince R, Gaich G, Reginster J . Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001; 344(19):1434-41. DOI: 10.1056/NEJM200105103441904. View

17.

Choi J, Konno T, Takai M, Ishihara K . Controlled drug release from multilayered phospholipid polymer hydrogel on titanium alloy surface. Biomaterials. 2009; 30(28):5201-8. DOI: 10.1016/j.biomaterials.2009.06.003. View

18.

Le Guehennec L, Soueidan A, Layrolle P, Amouriq Y . Surface treatments of titanium dental implants for rapid osseointegration. Dent Mater. 2006; 23(7):844-54. DOI: 10.1016/j.dental.2006.06.025. View

19.

Schuessele A, Mayr H, Tessmar J, Goepferich A . Enhanced bone morphogenetic protein-2 performance on hydroxyapatite ceramic surfaces. J Biomed Mater Res A. 2008; 90(4):959-71. DOI: 10.1002/jbm.a.31745. View

20.

Johnson M, Lee H, Bellamkonda R, Guldberg R . Sustained release of BMP-2 in a lipid-based microtube vehicle. Acta Biomater. 2008; 5(1):23-8. PMC: 3163463. DOI: 10.1016/j.actbio.2008.09.001. View