Despite its regenerative ability, long and segmental bone defect repair remains a significant orthopedic challenge. Conventional tissue engineering efforts induce bone formation through intramembranous ossification (IO) which limits vascular formation and leads to poor bone regeneration. To overcome this challenge, a novel hybrid matrix comprised of a load-bearing polymer template and a gel phase is designed and assessed for bone regeneration. Our previous studies developed a synthetic ECM, hyaluronan (HA)-fibrin (FB), that is able to mimic cartilage-mediated bone formation in vitro. In this study, the well-characterized HA-FB hydrogel is combined with a biodegradable polymer template to form a hybrid matrix. In vitro evaluation of the matrix showed cartilage template formation, cell recruitment and recruited cell osteogenesis, essential stages in endochondral ossification. A transgenic reporter-mouse critical-defect model was used to evaluate the bone healing potential of the hybrid matrix in vivo. The results demonstrated host cell recruitment into the hybrid matrix that led to new bone formation and subsequent remodeling of the mineralization. Overall, the study developed and evaluated a novel load-bearing graft system for bone regeneration via endochondral ossification.

中文翻译：

---

对通过内软骨骨化进行骨再生的工程杂交基质的评估。

尽管具有再生能力，但长期和节段性骨缺损修复仍是骨科的重大挑战。传统的组织工程工作通过膜内骨化（IO）诱导骨形成，从而限制了血管的形成并导致较差的骨再生。为了克服这一挑战，设计并评估了一种由负载聚合物模板和凝胶相组成的新型杂化基质，并对其骨再生进行了评估。我们以前的研究开发了一种合成的ECM，透明质酸（HA）-纤维蛋白（FB），它能够在体外模拟软骨介导的骨形成。在这项研究中，特征明确的HA-FB水凝胶与可生物降解的聚合物模板结合形成杂化基质。体外评估基质显示软骨模板形成，细胞募集和募集的细胞成骨，软骨内骨化的基本阶段 使用转基因报告基因-小鼠关键缺陷模型评估杂合基质在体内的骨愈合潜力。结果表明宿主细胞募集到混合基质中，导致新的骨形成和随后的矿化重塑。总的来说，该研究开发并评估了一种新型的通过软骨内骨化来进行骨再生的负重移植系统。