In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors

被引:63
作者
Gothard, David [1 ]
Smith, Emma L. [1 ]
Kanczler, Janos M. [1 ]
Black, Cameron R. [1 ]
Wells, Julia A. [1 ]
Roberts, Carol A. [1 ]
White, Lisa J. [2 ]
Qutachi, Omar [2 ]
Peto, Heather [2 ]
Rashidi, Hassan [2 ]
Rojo, Luis [4 ,5 ,6 ,7 ]
Stevens, Molly M. [4 ,5 ,6 ]
El Haj, Alicia J. [8 ]
Rose, Felicity R. A. J. [2 ]
Shakesheff, Kevin M. [2 ,3 ]
Oreffo, Richard O. C. [1 ]
机构
[1] Univ Southampton, Bone & Joint Res Grp, Ctr Human Dev Stem Cells & Regenerat, Inst Dev Sci, Southampton SO16 6YD, Hants, England
[2] Univ Nottingham, Wolfson Ctr Stem Cells Tissue Engn & Modelling, Sch Pharm, Ctr Biomol Sci, Nottingham NG7 2RD, England
[3] Locate Therapeut Ltd, MediCity, Nottingham NG90 6BH, England
[4] Univ London Imperial Coll Sci Technol & Med, Royal Sch Mines, Dept Mat, London SW7 2AZ, England
[5] Univ London Imperial Coll Sci Technol & Med, Dept Bioengn, London SW7 2AZ, England
[6] Univ London Imperial Coll Sci Technol & Med, Inst Biomed Engn, London SW7 2AZ, England
[7] Guys Hosp, Biomat Biomimet Biophoton Res Div, Kings Coll London, Inst Dent, London SE1 9RT, England
[8] Keele Univ, Inst Sci & Technol Med, Guy Hilton Res Ctr, Keele ST4 7BQ, Staffs, England
基金
英国生物技术与生命科学研究理事会;
关键词
FACTOR-RELEASING HYDROGELS; EXTRACELLULAR-MATRIX; CHONDROGENIC DIFFERENTIATION; OSTEOGENIC DIFFERENTIATION; MORPHOGENETIC PROTEIN-2; MECHANICAL-PROPERTIES; GRAFT SUBSTITUTES; COLLAGEN HYDROGEL; FACTOR DELIVERY; TISSUE-REPAIR;
D O I
10.1371/journal.pone.0145080
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-beta 3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors.
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页数:23
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