Béduer Amélie, Genta Martina, Kunz Nicolas, Verheyen Connor, Martins Mariana, Brefie-Guth Joé, Braschler Thomas
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CMU, Rue Michel-Servet 1, 1211 Genève 4, Switzerland; Volumina-Medical SA, Route de la Corniche 5, CH-1066 Epalinges, Switzerland.
Laboratory of Microsystems 4, STI-IMT, Station 17, EPFL, 1015 Lausanne, Switzerland.
Acta Biomater. 2022 Apr 1;142:73-84. doi: 10.1016/j.actbio.2022.01.050. Epub 2022 Jan 31.
Soft tissue reconstruction currently relies on two main approaches, one involving the implantation of external biomaterials and the second one exploiting surgical autologous tissue displacement. While both methods have different advantages and disadvantages, successful long-term solutions for soft tissue repair are still limited. Specifically, volume retention over time and local tissue regeneration are the main challenges in the field. In this study the performance of a recently developed elastic porous injectable (EPI) biomaterial based on crosslinked carboxymethylcellulose is analyzed. Nearly quantitative volumetric stability, with over 90% volume retention at 6 months, is observed, and the pore space of the material is effectively colonized with autologous fibrovascular tissue. A comparative analysis with hyaluronic acid and collagen-based clinical reference materials is also performed. Mechanical stability, evidenced by a low-strain elastic storage modulus (G') approaching 1kPa and a yield strain of several tens of percent, is required for volume retention in-vivo. Macroporosity, along with in-vivo persistence of at least several months, is instead needed for successful host tissue colonization. This study demonstrates the importance of understanding material design criteria and defines the biomaterial requirements for volume retention and tissue colonization in soft tissue regeneration. STATEMENT OF SIGNIFICANCE: We present the design of an elastic, porous, injectable (EPI) scaffold suspension capable of inducing a precisely defined, stable volume of autologous connective tissue in situ. It combines volume stability and vascularized tissue induction capacity known from bulk scaffolds with the ease of injection in shear yielding materials. By comparative study with a series of clinically established biomaterials including a wound healing matrix and dermal fillers, we establish design rules regarding rheological and compressive mechanical properties as well as degradation characteristics that rationally underpin the volume stability and tissue induction in a high-performance biomaterial. These design rules should allow to streamline the development of new colonizable injectables.
软组织重建目前主要依赖两种方法，一种是植入外部生物材料，另一种是利用手术自体组织移位。虽然这两种方法都有不同的优缺点，但软组织修复的成功长期解决方案仍然有限。具体而言，随着时间的推移保持体积以及局部组织再生是该领域的主要挑战。在本研究中，分析了一种基于交联羧甲基纤维素的新型弹性多孔可注射（EPI）生物材料的性能。观察到几乎定量的体积稳定性，在6个月时体积保留率超过90%，并且材料的孔隙空间被自体纤维血管组织有效占据。还与透明质酸和胶原蛋白基临床参考材料进行了对比分析。体内保持体积需要机械稳定性，表现为低应变弹性储能模量（G'）接近1kPa且屈服应变为百分之几十。相反，成功的宿主组织定植需要大孔隙率以及至少几个月的体内持久性。本研究证明了理解材料设计标准的重要性，并定义了软组织再生中体积保持和组织定植的生物材料要求。重要性声明：我们展示了一种弹性、多孔、可注射（EPI）支架悬浮液的设计，该悬浮液能够在原位诱导精确确定的稳定体积的自体结缔组织。它将块状支架已知的体积稳定性和血管化组织诱导能力与剪切屈服材料中易于注射的特性相结合。通过与一系列临床确立的生物材料（包括伤口愈合基质和真皮填充剂）进行对比研究，我们建立了关于流变学和压缩力学性能以及降解特性的设计规则，这些规则合理地支撑了高性能生物材料中的体积稳定性和组织诱导。这些设计规则应有助于简化新型可定植可注射材料的开发。
