Ogueri Kenneth S, Allcock Harry R, Laurencin Cato T
Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.
Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Prog Polym Sci. 2019 Nov;98. doi: 10.1016/j.progpolymsci.2019.101146. Epub 2019 Aug 9.
New fields such as regenerative engineering have driven the design of advanced biomaterials with a wide range of properties. Regenerative engineering is a multidisciplinary approach that integrates the fields of advanced materials science and engineering, stem cell science, physics, developmental biology, and clinical translation for the regeneration of complex tissues. The complexity and demands of this innovative approach have motivated the synthesis of new polymeric materials that can be customized to meet application-specific needs. Polyphosphazene polymers represent this fundamental change and are gaining renewed interest as biomaterials due to their outstanding synthetic flexibility, neutral bioactivity (buffering degradation products), and tunable properties across the range. Polyphosphazenes are a unique class of polymers composed of an inorganic backbone with alternating phosphorus and nitrogen atoms. Each phosphorus atom bears two substituents, with a wide variety of side groups available for property optimization. Polyphosphazenes have been investigated as potential biomaterials for regenerative engineering. Polyphosphazenes for use in regenerative applications have evolved as a class to include different generations of degradable polymers. The first generation of polyphosphazenes for tissue regeneration entailed the use of hydrolytically active side groups such as imidazole, lactate, glycolate, glucosyl, or glyceryl groups. These side groups were selected based on their ability to sensitize the polymer backbone to hydrolysis, which allowed them to break down into non-toxic small molecules that could be metabolized or excreted. The second generation of degradable polyphosphazenes developed consisted of polymers with amino acid ester side groups. When blended with poly (lactic acid-co-glycolic acid) (PLGA), the feasibility of neutralizing acidic degradation products of PLGA was demonstrated. The blends formed were mostly partially miscible. The desire to improve miscibility led to the design of the third generation of degradable polyphosphazenes by incorporating dipeptide side groups which impart significant hydrogen bonding capability to the polymer for the formation of completely miscible polyphosphazene-PLGA blends. Blend system of the dipeptide-based polyphosphazene and PLGA exhibit a unique degradation behavior that allows the formation of interconnected porous structures upon degradation. These inherent pore-forming properties have distinguished degradable polyphosphazenes as a potentially important class of biomaterials for further study. The design considerations and strategies for the different generations of degradable polyphosphazenes and future directions are discussed.
再生工程等新领域推动了具有广泛特性的先进生物材料的设计。再生工程是一种多学科方法，它整合了先进材料科学与工程、干细胞科学、物理学、发育生物学以及用于复杂组织再生的临床转化等领域。这种创新方法的复杂性和需求促使人们合成新的聚合物材料，这些材料可以定制以满足特定应用的需求。聚磷腈聚合物代表了这一根本性变化，并且由于其出色的合成灵活性、中性生物活性（缓冲降解产物）以及广泛的可调谐特性，作为生物材料正重新引起人们的兴趣。聚磷腈是一类独特的聚合物，由具有交替磷和氮原子的无机主链组成。每个磷原子带有两个取代基，有各种各样的侧基可用于性能优化。聚磷腈已被研究作为再生工程的潜在生物材料。用于再生应用的聚磷腈已发展成为一类，包括不同代的可降解聚合物。第一代用于组织再生的聚磷腈需要使用水解活性侧基，如咪唑、乳酸、乙醇酸、葡萄糖基或甘油基。选择这些侧基是基于它们使聚合物主链对水解敏感的能力，这使得它们能够分解成无毒的小分子，这些小分子可以被代谢或排泄。第二代开发的可降解聚磷腈由具有氨基酸酯侧基的聚合物组成。当与聚（乳酸 - 乙醇酸共聚物）（PLGA）共混时，证明了中和PLGA酸性降解产物的可行性。形成的共混物大多是部分互溶的。为了提高互溶性，人们通过引入二肽侧基设计了第三代可降解聚磷腈，二肽侧基赋予聚合物显著的氢键能力，从而形成完全互溶的聚磷腈 - PLGA共混物。基于二肽的聚磷腈和PLGA的共混体系表现出独特的降解行为，降解时允许形成相互连接的多孔结构。这些固有的成孔特性使可降解聚磷腈成为一类潜在的重要生物材料，有待进一步研究。本文讨论了不同代可降解聚磷腈的设计考虑因素、策略以及未来发展方向。
