Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208.
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611.
Proc Natl Acad Sci U S A. 2024 Aug 13;121(33):e2405454121. doi: 10.1073/pnas.2405454121. Epub 2024 Aug 6.
Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor β-1 (TGFβ-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues. The scaffold is an injectable slurry that generates a porous rubbery material when exposed to calcium ions once placed in cartilage defects. The hybrid material was found to support in vitro chondrogenic differentiation of encapsulated stem cells in response to sustained delivery of TGFβ-1. Using a sheep model, we implanted the scaffold in shallow osteochondral defects and found it can remain localized in mechanically active joints. Evaluation of resected joints showed significantly improved repair of hyaline cartilage in osteochondral defects injected with the scaffold relative to defects injected with the growth factor alone, including implantation in the load-bearing femoral condyle. These results demonstrate the potential of the hybrid biomimetic scaffold as a niche to favor cartilage repair in mechanically active joints using a clinically relevant large-animal model.
在人类大小的关节中再生透明软骨仍然是一个临床挑战，这是一个亟待满足的关键需求，将有助于延长健康寿命。能够将生物活性和足够坚固的物理性能相结合，以承受关节压力的用于软骨修复的可注射支架提供了一种很有前途的策略。我们在这里报告了一种混合生物材料，它结合了一种具有生物活性的肽两亲超分子聚合物，该聚合物特异性结合软骨生成细胞因子转化生长因子 β-1（TGFβ-1），以及交联透明质酸微凝胶，后者可驱动纤维束的形成，纤维束是天然肌肉骨骼组织中常见的分级结构。该支架是一种可注射的浆料，一旦放置在软骨缺陷中，暴露于钙离子时会生成多孔橡胶状材料。该混合材料被发现支持包封干细胞的体外软骨分化，以响应持续递送 TGFβ-1。使用绵羊模型，我们将支架植入浅骨软骨缺损中，发现它可以在机械活跃的关节中保持局部定位。对切除的关节进行评估表明，与单独注射生长因子的缺陷相比，注射支架的骨软骨缺陷中的透明软骨修复得到了显著改善，包括在承重的股骨髁上的植入。这些结果表明，这种混合仿生支架作为一种小生境，具有在使用临床相关大动物模型的机械活跃关节中促进软骨修复的潜力。
