Background Demineralized bone matrix (DBM), an allograft bone processed to better expose osteoinductive factors such as bone morphogenetic proteins (BMPs), is increasingly used for clinical bone repair. However, more extensive use of DBM is limited by its unpredictable osteoinductivity and low bone formation capacity. Commercial DBM products often employ polymeric carriers to enhance handling properties but such carriers generally do not possess bioactive functions. Heparin is a highly sulfated polysaccharide and is shown to form a stable complex with growth factors to enhance their bioactivities. In this study, a new heparinized synthetic carrier for DBM is developed based on photocrosslinking of methacrylated glycol chitosan and heparin conjugation. Results Heparinized chitosan exerts protective effects on BMP bioactivity against physiological stressors related to bone fracture healing. It also enhances the potency of BMPs by inhibiting the activity of BMP antagonist, noggin. Moreover, heparinized chitosan is effective to deliver bone marrow stromal cells and DBM for enhanced osteogenesis by sequestering and localizing the cell-produced or DBM-released BMPs. Conclusions This research suggests an essential approach of developing a new hydrogel carrier to stabilize the bioactivity of BMPs and improve the clinical efficacy of current bone graft therapeutics for accelerated bone repair.

中文翻译：

---

肝素化壳聚糖可稳定 BMP-2 的生物活性并增强脱矿质骨基质的成骨功效。

背景 脱矿质骨基质 (DBM) 是一种同种异体骨，经过加工可以更好地暴露骨形态发生蛋白 (BMP) 等骨诱导因子，越来越多地用于临床骨修复。然而，DBM 的更广泛使用受到其不可预测的骨诱导性和低骨形成能力的限制。商业 DBM 产品通常使用聚合物载体来增强处理性能，但此类载体通常不具有生物活性功能。肝素是一种高度硫酸化的多糖，可与生长因子形成稳定的复合物以增强其生物活性。在这项研究中，基于甲基丙烯酸化乙二醇壳聚糖和肝素偶联物的光交联，开发了一种用于 DBM 的新型肝素化合成载体。结果肝素化壳聚糖对与骨折愈合相关的生理应激源的BMP生物活性具有保护作用。它还通过抑制 BMP 拮抗剂 noggin 的活性来增强 BMP 的效力。此外，肝素化壳聚糖通过隔离和定位细胞产生或 DBM 释放的 BMP，可有效递送骨髓基质细胞和 DBM，以增强骨生成。结论 本研究提出了开发一种新的水凝胶载体以稳定 BMP 的生物活性并提高当前骨移植治疗加速骨修复的临床疗效的基本方法。肝素化壳聚糖通过隔离和定位细胞产生或 DBM 释放的 BMP，可有效递送骨髓基质细胞和 DBM，以增强成骨。结论 本研究提出了开发一种新的水凝胶载体以稳定 BMP 的生物活性并提高当前骨移植治疗加速骨修复的临床疗效的基本方法。肝素化壳聚糖通过隔离和定位细胞产生或 DBM 释放的 BMP，可有效递送骨髓基质细胞和 DBM，以增强成骨。结论 本研究提出了开发一种新的水凝胶载体以稳定 BMP 的生物活性并提高当前骨移植治疗加速骨修复的临床疗效的基本方法。