In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors.
In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors.
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DOI：
10.1371/journal.pone.0145080
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Oreffo RO
中科院分区：
文献类型：
--
作者：
Gothard D;Smith EL;Kanczler JM;Black CR;Wells JA;Roberts CA;White LJ;Qutachi O;Peto H;Rashidi H;Rojo L;Stevens MM;El Haj AJ;Rose FR;Shakesheff KM;Oreffo RO
目前的研究调查了脱细胞、脱矿化骨细胞外基质(ECM)水凝胶结构在体内组织矿化和骨形成中的应用。将Stro-1富集人骨髓基质细胞与血管内皮生长因子、转化生长因子-β-3、骨形态发生蛋白-2、PTHrP和VitD3复合，以促进骨形成，并与藻酸盐混合作为结构支撑。生长因子通过快(非成骨因子)和慢(成骨因子)PLGA微粒释放。将5 mm长的构建物植入小鼠体内28天。显微CT评估的致密组织与组织学评估的所有结构的矿化骨形成相关。与单独添加藻酸盐/骨细胞外基质(ALG/ECM)水凝胶相比，添加外源生长因子并不能进一步促进骨形成。紫外线照射通过降解骨细胞外基质成分中的内在生长因子以及可能的细胞外基质交联物来减少骨形成。BMP-2和VitD3挽救了成骨诱导。ALG/ECM水凝胶显示出高度的骨诱导性，血管生成或软骨生成生长因子的输送导致骨形成的改变。所有结构均显示广泛的宿主组织侵袭和血管化，有助于整合和种植体寿命。所提出的水凝胶系统无需生长因子掺入或外源可诱导细胞来源即可发挥作用。最佳生长因子浓度和时空释放曲线需要进一步评估，因为骨细胞外基质成分可能在供体材料之间存在批次差异。总之，ALG/ECM水凝胶提供了一种在再生医学中使用的多功能生物材料支架，最终可以通过加入特定的生长因子来定制以形成选择的组织。
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-β3, 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.