期刊
BIOMATERIALS
卷 188, 期 -, 页码 38-49出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.10.004
关键词
BMP-2; Zoledronic acid; Collagen membrane; Metaphyseal defect; Cortical defect
资金
- Region Skane (ALF), Sweden
- VINNOVA
- Swedish agency for innovation systems [2017-00269]
- Swedish Research Council [2015-06717]
- Department of Science and Technology, Government of India [DST/INT/SWD/P-11/2016]
- Department of Biotechnology, Government of India [BT/IN/Sweden/08/AK/2017-18]
- Vinnova [2017-00269] Funding Source: Vinnova
- Swedish Research Council [2015-06717] Funding Source: Swedish Research Council
- Forte [2017-00269] Funding Source: Forte
A metaphyseal bone defect due to infection, tumor or fracture leads to loss of cancellous and cortical bone. An animal model separating the cancellous and cortical healing was used with a combination of a macroporous gelatin-calcium sulphate-hydroxyapatite (Gel-CaS-HA) biomaterial as a cancellous defect filler, and a thin collagen membrane (CM) guiding cortical bone regeneration. The membrane was immobilized with bone morphogenic protein-2 (rhBMP-2) to enhance the osteoinductive properties. The Gel-CaS-HA cancellous defect filler contained both rhBMP-2 and a bisphosphonate, (zoledronate = ZA) to prevent premature callus resorption induced by the pro-osteoclast effect of rhBMP-2 alone. In the first part of the study, the CM delivering both rhBMP-2 and ZA was tested in a muscle pouch model in rats and the co-delivery of rhBMP-2 and ZA via the CM resulted in higher amounts of bone compared to rhBMP-2 alone. Secondly, an established tibia defect model in rats was used to study cortical and cancellous bone regeneration. The defect was left empty, filled with Gel-CaS-HA alone, Gel-CaS-HA immobilized with ZA or Gel-CaS-HA immobilized with rhBMP-2+ ZA. Functionalization of the Gel-CaS-HA scaffold with bioactive molecules produced significantly more bone in the cancellous defect and its surroundings but cortical defect healing was delayed likely due to the protrusion of the Gel-CaS-HA into the cortical bone. To guide cortical regeneration, the cortical defect was sealed endosteally by a CM with or without rhBMP-2. Subsequently, the cancellous defect was filled with Gel-CaS-HA containing ZA and rhBMP2 + ZA. In the groups where the CM was doped with rhBMP-2, significantly higher number of cortices bridged. The approach to guide cancellous as well as cortical bone regeneration separately in a metaphyseal defect using two bioactive molecule immobilized biomaterials is promising and could improve the clinical care of patients with metaphyseal defects.
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