Demonstration of therapeutic effect of plasma-synthesized polypyrrole/iodine biopolymer in rhesus monkey with complete spinal cord section

IF 4.5 3区医学 Q2 ENGINEERING, BIOMEDICAL

Journal of Materials Science: Materials in Medicine Pub Date : 2025-02-17 DOI:10.1007/s10856-025-06862-x

Camilo Ríos, Hermelinda Salgado-Ceballos, Israel Grijalva, Axayacatl Morales-Guadarrama, Araceli Diaz-Ruiz, Roberto Olayo, Juan Morales-Corona, María G. Olayo, Guillermo J. Cruz, Rodrigo Mondragón-Lozano, Laura Alvarez-Mejia, Carlos Orozco-Barrios, Stephanie Sánchez-Torres, Omar Fabela-Sánchez, Angélica Coyoy-Salgado, Braulio Hernández-Godínez, Alejandra Ibáñez-Contreras, Marisela Mendez-Armenta

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引用次数: 0

Abstract

Spinal cord injury (SCI) can cause paralysis, and although multiple therapeutic proposals have been developed in murine models, results have hardly been replicated in humans. As non-human primates (NHP) are more similar to humans than rodents, the current study investigated whether it was possible to reproduce in a NHP, the previously obtained beneficial results by using a plasma-synthesized polypyrrole/iodine (PPy/I) biopolymer, which reduce glial scar formation and inflammatory response and promotes nerve tissue preservation, regenerative processes and functional recovery in rats. In NHPs (Rhesus monkey) with SCI by complete transection (SCT) and with plasma-synthesized PPy/I application (experimental) or without (control), the expression of pro-inflammatory cytokines in blood, preservation of nervous tissue through magnetic resonance imaging and histological and morphometric techniques, regeneration through immunohistochemistry study and functional recovery through clinical examination, were evaluated. Control NHP showed a markedly increased of pro-inflammatory cytokines vs. experimental NHP, which preserved more nerve tissue. At the end of the follow-up, a thinner glial scar in the injured spinal cord was observed in the experimental NHP as well as regenerative nerve processes (NeuN and β-III tubulin expression), while control NHP had a marked glial scar, large cysts and less nerve tissue at the injured zone. Plasma-synthesized PPy/I also reduced the loss of pelvic limb muscle mass and allowed the experimental NHP recovered knee-jerk, withdrawal and plantar reflexes as well as movement in the hind limbs. Since most of the beneficial effects of plasma-synthesized PPy/I previously reported in rats were also observed in the NHP, these preliminary findings make their replication in humans with SCI more likely.

Graphical Abstract

Abstract Image

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血浆合成聚吡咯/碘生物聚合物对恒河猴脊髓完整切片的疗效观察

脊髓损伤（SCI）可导致瘫痪，尽管在小鼠模型中已经提出了多种治疗方案，但结果几乎无法在人类中复制。由于非人类灵长类动物（NHP）比啮齿类动物更接近人类，本研究调查了是否有可能在非人类灵长类动物（NHP）中繁殖，先前通过使用血浆合成的聚吡咯/碘（PPy/I）生物聚合物获得的有益结果，该聚合物可以减少大鼠神经胶质疤痕形成和炎症反应，促进神经组织保存，再生过程和功能恢复。在采用全横断（SCT）、血浆合成PPy/I应用（实验）或不应用（对照）的脊髓损伤的恒河猴（NHPs）中，评估血液中促炎细胞因子的表达、通过磁共振成像和组织学和形态计量技术保存的神经组织、通过免疫组织化学研究的再生和通过临床检查的功能恢复。对照NHP与实验NHP相比，显示出明显增加的促炎细胞因子，保留了更多的神经组织。随访结束时，实验NHP损伤脊髓的胶质瘢痕变薄，再生神经突（NeuN和β-III微管蛋白表达）也变薄，而对照组NHP损伤区胶质瘢痕明显，囊肿较大，神经组织较少。血浆合成的PPy/I还减少了骨盆肢体肌肉质量的损失，并使实验性NHP恢复了膝跳、退缩和足底反射以及后肢的运动。由于之前在大鼠中报道的血浆合成PPy/I的大多数有益作用也在NHP中观察到，这些初步发现使得它们更有可能在SCI患者中复制。图形抽象

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来源期刊

Journal of Materials Science: Materials in Medicine 工程技术-材料科学：生物材料

CiteScore

8.00

自引率

0.00%

发文量

审稿时长

3.5 months

期刊介绍： The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.