Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland.
Adv Healthc Mater. 2015 Dec 9;4(17):2649-56. doi: 10.1002/adhm.201500439. Epub 2015 Sep 28.
Defects within bones caused by trauma and other pathological complications may often require the use of a range of therapeutics to facilitate tissue regeneration. A number of approaches have been widely utilized for the delivery of such therapeutics via physical encapsulation or chemical immobilization suggesting significant promise in the healing of bone defects. The study focuses on the chemical immobilization of osteostatin, a pentapeptide of the parathyroid hormone (PTHrP107-111), within a collagen-hydroxyapatite scaffold. The chemical attachment method via crosslinking supports as little as 4% release of the peptide from the scaffolds after 21 d whereas non-crosslinking leads to 100% of the peptide being released by as early as 4 d. In vitro characterization demonstrates that this cross-linking method of immobilization supports a pro-osteogenic effect on osteoblasts. Most importantly, when implanted in a critical-sized calvarial defect within a rat, these scaffolds promote significantly greater new bone volume and area compared to nonfunctionalized scaffolds (**p < 0.01) and an empty defect control (***p < 0.001). Collectively, this study suggests that such an approach of chemical immobilization offers greater spatiotemporal control over growth factors and can significantly modulate tissue regeneration. Such a system may be adopted for a range of different proteins and thus offers the potential for the treatment of various complex pathologies that require localized mediation of drug delivery.
由创伤和其他病理并发症引起的骨骼缺陷通常需要使用一系列治疗方法来促进组织再生。许多方法已被广泛用于通过物理包封或化学固定化来递送这些治疗剂，这表明在治疗骨缺陷方面具有很大的潜力。本研究专注于将骨抑素（甲状旁腺激素（PTHrP107-111）的五肽）通过化学固定化方法固定在胶原-羟基磷灰石支架内。化学交联方法通过交联支持在 21 天内从支架中释放低至 4%的肽，而不交联则导致最早在 4 天内释放 100%的肽。体外特性表明，这种固定化的交联方法对成骨细胞具有促成骨作用。最重要的是，当在大鼠的临界颅骨缺损中植入这些支架时，与非功能化支架相比（**p < 0.01）和空缺陷对照（***p < 0.001），这些支架显著促进了更多的新骨体积和面积。总的来说，这项研究表明，这种化学固定化方法为生长因子提供了更大的时空控制，并可以显著调节组织再生。这种系统可用于多种不同的蛋白质，因此为需要局部药物输送介导的各种复杂病理提供了治疗的潜力。
