Galarraga Jonathan H, Zlotnick Hannah M, Locke Ryan C, Gupta Sachin, Fogarty Natalie L, Masada Kendall M, Stoeckl Brendan D, Laforest Lorielle, Castilho Miguel, Malda Jos, Levato Riccardo, Carey James L, Mauck Robert L, Burdick Jason A
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Int J Bioprint. 2023 Jun 14;9(5):775. doi: 10.18063/ijb.775. eCollection 2023.
The surgical repair of articular cartilage remains an ongoing challenge in orthopedics. Tissue engineering is a promising approach to treat cartilage defects; however, scaffolds must (i) possess the requisite material properties to support neocartilage formation, (ii) exhibit sufficient mechanical integrity for handling during implantation, and (iii) be reliably fixed within cartilage defects during surgery. In this study, we demonstrate the reinforcement of soft norbornene-modified hyaluronic acid (NorHA) hydrogels via the melt electrowriting (MEW) of polycaprolactone to fabricate composite scaffolds that support encapsulated porcine mesenchymal stromal cell (pMSC, three donors) chondrogenesis and cartilage formation and exhibit mechanical properties suitable for handling during implantation. Thereafter, acellular MEW-NorHA composites or MEW-NorHA composites with encapsulated pMSCs and precultured for 28 days were implanted in full-thickness cartilage defects in porcine knees using either bioresorbable pins or fibrin glue to assess surgical fixation methods. Fixation of composites with either biodegradable pins or fibrin glue ensured implant retention in most cases (80%); however, defects treated with pinned composites exhibited more subchondral bone remodeling and inferior cartilage repair, as evidenced by micro-computed tomography (micro-CT) and safranin O/fast green staining, respectively, when compared to defects treated with glued composites. Interestingly, no differences in repair tissue were observed between acellular and cellularized implants. Additional work is required to assess the full potential of these scaffolds for cartilage repair. However, these results suggest that future approaches for cartilage repair with MEW-reinforced hydrogels should be carefully evaluated with regard to their fixation approach for construct retention and surrounding cartilage tissue damage.
关节软骨的手术修复仍是骨科领域持续面临的一项挑战。组织工程是治疗软骨缺损的一种很有前景的方法;然而,支架必须(i)具备支持新软骨形成所需的材料特性,(ii)在植入过程中具备足够的机械完整性以便操作,以及(iii)在手术过程中能可靠地固定在软骨缺损处。在本研究中,我们通过聚己内酯的熔体电写(MEW)来增强软质降冰片烯修饰的透明质酸(NorHA)水凝胶,以制备复合支架,该复合支架能支持封装的猪间充质基质细胞(pMSC,来自三个供体)的软骨形成和软骨生成,并展现出适合植入操作的机械性能。此后,使用可生物吸收的销钉或纤维蛋白胶,将脱细胞的MEW-NorHA复合材料或封装有pMSC并预培养28天的MEW-NorHA复合材料植入猪膝关节的全层软骨缺损处,以评估手术固定方法。在大多数情况下(80%),使用可生物降解销钉或纤维蛋白胶固定复合材料可确保植入物留存;然而,与使用胶合复合材料治疗的缺损相比,分别通过微型计算机断层扫描(micro-CT)和番红O/固绿染色证明,用销钉固定复合材料治疗的缺损表现出更多的软骨下骨重塑和较差的软骨修复效果。有趣的是,在脱细胞植入物和细胞化植入物之间未观察到修复组织的差异。评估这些支架用于软骨修复的全部潜力还需要开展更多工作。然而,这些结果表明,未来使用MEW增强水凝胶进行软骨修复的方法,应就其用于构建物留存和周围软骨组织损伤的固定方法进行仔细评估。