周圍神經損傷（PNI）是對周圍神經系統（PNS）損害的總稱，可能由於過度的外部力量引起，導致神經系統內信號傳遞的異常、錯誤或中斷。嚴重的PNI需要干預以協助神經再生。目前的治療方法包括自體移植、同種移植和異種移植，但這些方法都存在二次手術、與接受者不相符以及供體來源稀缺等不便之處。針對這一未滿足需求，我們建立一種生物相容性和可降解的導管，並添加藥物以促進PNI的恢復。
在本研究中，我們通過對聚乙二醇（PEG）進行甲基丙烯酸化修飾，合成了一種可光固化聚合物PEGDMA，並與光起始劑Irgacure 2959結合，以建立聚合物水凝膠網絡（PEGDMA）。為了在親水性水凝膠中攜帶疏水性藥物雷帕霉素（RAPA），我們成功將RAPA包裹到聚乳酸-聚乙烯醇（PLGA）中，形成親水性RAPA-PLGA奈米顆粒（RNP NPs）。透過將RNP NPs整合到水凝膠網絡中（RNP NPs@PEGDMA），其機械性能通過在其表面塗覆單寧酸得到增強。FTIR結果表明，在整合後，RAPA的特徵峰在RNP NPs@PEGDMA-TA中仍然存在，顯示出RNP NPs與光固化系統之間的良好結合。
RNP NPs@PEGDMA-TA的機械性能通過拉伸測試結果得到確認，此外，透過14天的膨脹測試其在水溶液中極佳的穩定性，並且透過8 周的降解實驗中，顯示其能夠維持型態完整性同時降解。RNP NPs@PEGDMA-TA 經過 72 小時的共同培養後，其細胞毒性實驗顯示出良好的細胞存活率。在 H₂O₂ 誘導的損傷後，RNP NPs@PEGDMA-TA 能夠有效促進自噬，通過 Beclin-1 的高表達量證實了其效果，並通過 GAP43 的高表現量闡明了自噬與氧化損傷後細胞再生之間的聯繫。
我們成功開發了一種攜帶藥物的光固化聚合物網絡：RNP NPs@PEGDMA-TA 水凝膠。體外實驗表明，該材料能夠增強自噬，同時展現出適用於周邊神經損傷治療的良好物理和機械性能。此方法未來在促進軸突再生，甚至神經再生方面，或將展現出良好的可行性。

Peripheral nerve injury (PNI) is a general term for damage to the peripheral nervous system (PNS), which may occur due to excessive external force, leading to aberrant, mistaken, or discontinuous signal transmission within the nervous system. Severe PNI requires intervention to assist in nerve regeneration. Current treatments include autografts, allografts, and xenografts, all of which involve inconveniences such as secondary surgeries, misfit to the recipient, and rare donor sources. A strategy to address this unmet need is the establishment of a biocompatible and biodegradable conduit with drugs to aid in the recovery of PNI.
In this study, we synthesized a photocurable polymer, monomer PEGDMA, through the methacrylation of PEG, combined with the photoinitiator Irgacure 2959 to create a polymeric hydrogel network (PEGDMA). To carry the hydrophobic drug rapamycin (RAPA) within the hydrophilic hydrogel, we successfully encapsulated RAPA into PLGA, forming hydrophilic RAPA-PLGA nanoparticles (RNP NPs). The RNP NPs were then integrated into the hydrogel network (RNP NPs@PEGDMA), whose mechanical properties were enhanced by coating it with a layer of tannic acid (TA). FTIR results indicated that after integration, the characteristic peaks of RAPA remained in RNP NPs@PEGDMA-TA, demonstrating a proper combination between RNP NPs and the photocuring system.
The mechanical properties of RNP NPs@PEGDMA-TA were confirmed by tensile test results, showing greater durability than standard sutures. The swelling ratio was minimal after 14 days of immersion, and the mass after degradation remained at 43.10% of the initial weight, demonstrating its ability to degrade without fracture over 8 weeks. The cytotoxicity of RNP NPs@PEGDMA-TA extracts exhibited well viability after 72 hours of co-incubation. The ability to improve autophagy following H₂O₂-induced damage was evidenced by the high expression of Beclin-1, and the connection between autophagy and cell regeneration after oxidative injury was clarified by the high expression of GAP43 after RNP NPs@PEGDMA-TA extraction treatment.
We successfully developed a drug-loaded photocuring polymer network, RNP NPs@PEGDMA-TA hydrogel. In vitro experiments demonstrated its capacity to enhance autophagy, while also exhibiting favorable physical and mechanical properties for potential application in the treatment of peripheral nerve injury (PNI). This approach may prove effective in promoting axon regeneration and, ultimately, nerve regeneration in the future.

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