Shoaib Muhammad M, Huynh Vincent, Shad Yousuf, Ahmed Rashik, Jesmer Alexander H, Melacini Giuseppe, Wylie Ryan G
Department of Chemistry and Chemical Biology, McMaster University Hamilton Ontario L8S 4M1 Canada
Department of Biochemistry and Biomedical Sciences, McMaster University Hamilton Ontario L8S 4M1 Canada.
RSC Adv. 2019 Jun 17;9(33):18978-18988. doi: 10.1039/c9ra03441b. eCollection 2019 Jun 14.
Degradable low-fouling hydrogels are ideal vehicles for drug and cell delivery. For each application, hydrogel degradation rate must be re-optimized for maximum therapeutic benefit. We developed a method to rapidly and predictably tune degradation rates of low-fouling poly(oligo(ethylene glycol)methyl ether methacrylate) (P(EG) MA) hydrogels by modifying two interdependent variables: (1) base-catalysed crosslink degradation kinetics, dependent on crosslinker electronics (electron withdrawing groups (EWGs)); and, (2) polymer hydration, dependent on the molecular weight ( ) of poly(ethylene glycol) (PEG) pendant groups. By controlling PEG and EWG strength, P(EG) MA hydrogels were tuned to degrade over 6 to 52 d. A 6-member P(EG) MA copolymer library yielded slow and fast degrading low-fouling hydrogels suitable for short- and long-term delivery applications. The degradation mechanism was also applied to RGD-functionalized poly(carboxybetaine methacrylamide) (PCBMAA) hydrogels to achieve slow (∼50 d) and fast (∼13 d) degrading low-fouling, bioactive hydrogels.
可降解的低污染水凝胶是药物和细胞递送的理想载体。对于每种应用,必须重新优化水凝胶的降解速率以实现最大治疗效果。我们开发了一种方法,通过改变两个相互依存的变量,快速且可预测地调节低污染聚(寡聚(乙二醇)甲基丙烯酸甲酯)(P(EG)MA)水凝胶的降解速率:(1)碱催化的交联降解动力学,取决于交联剂电子效应(吸电子基团(EWG));以及(2)聚合物水合作用,取决于聚(乙二醇)(PEG)侧基的分子量( )。通过控制PEG 和EWG强度,将P(EG)MA水凝胶调节为在6至52天内降解。一个由6种P(EG)MA共聚物组成的文库产生了适合短期和长期递送应用的降解缓慢和快速的低污染水凝胶。降解机制也应用于RGD功能化的聚(甲基丙烯酰基羧酸甜菜碱)(PCBMAA)水凝胶,以实现降解缓慢(约50天)和快速(约13天)的低污染、生物活性水凝胶。