• Suppr超能文献
  • 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
定价套餐&价格
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Win 客户端微信小程序
定价
会员套餐积分包API 积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026
  1. 首页
  3. 分享广场
  5. 胶原包入微球的研究进展及在医美中的应用

胶原包入微球的研究进展及在医美中的应用

文献检索匿名用户发表于 2026年03月05日 15:5318阅读
检索问题

将胶原包入微球的研究进展及在医美中的应用

胶原包入微球的研究进展及其在医美中的应用

胶原蛋白作为一种重要的生物材料，在医学美容领域，特别是在皮肤填充剂方面，一直占据着重要的地位。然而，传统胶原填充剂存在降解快、胶原再生效果不足以及需要高频率注射等局限性。为了克服这些缺点并增强其在医美中的应用效果，研究人员致力于开发将胶原包入微球的策略，以实现更持久、更有效的胶原再生和更好的美学效果。

一、 胶原包入微球的策略与进展

将胶原包入微球的研究主要集中在以下几个方面：

  1. 胶原与其他生物材料复合微球的构建

    • 胶原@PLLA复合微球： 一种策略是将交联胶原膨胀在弱酸性溶液中，并涂覆在聚L-乳酸（PLLA）微球表面，形成胶原@PLLA复合微球（Col@PLLA）。这些复合微球随后分散在羧甲基纤维素钠（CMC）水溶液中，冻干后形成多孔海绵。研究表明，与单独的胶原和PLLA微球相比，Col@PLLA复合填充剂在注射5天后显示出显著的胶原再生，再生出的III型和I型胶原在植入4个月后仍保持较高水平，炎症反应也验证了其再生机制和长效潜力。这种方法旨在通过PLLA微球的刺激作用和胶原的即时填充及生物相容性，实现快速且长期的胶原再生。

    • PLLA微球分散在HA/胶原水凝胶中： 另一种设计是构建包含多孔PLLA微球和氨甲环酸（TXA）的再生性真皮填充剂，其中PLLA微球分散在交联透明质酸（HA）和胶原组成的复合水凝胶基质中。这种设计旨在提供即时和持久的填充效果。水凝胶基质通过皮内注射实现皱纹填充，TXA释放以发挥美白作用，而多孔PLLA微球及其降解产物乳酸则持续刺激胶原再生。研究发现，注射后立即面部体积增加，并生成大量I型和III型新胶原。PLLA微球的多孔结构促进了胶原纤维的“穿透生长”，有效填充面部凹陷并抚平皱纹。

    • 胶原/明胶/羟乙基纤维素复合材料与微球： 也有研究致力于开发三维胶原/明胶/羟乙基纤维素复合材料与明胶或胶原-明胶负载微球的组合。这些微球通过乳化/交联方法制备，并使用1-乙基-3-(3-二甲基氨丙基)-碳二亚胺（EDC）和N-羟基琥珀酰亚胺（NHS）混合物作为交联剂。扫描电子显微镜（SEM）图像显示微球呈球形，不规则地分散在聚合物基质中。添加微粒对材料的微观结构没有显著改变，但略微降低了基质的溶胀性，并增加了杨氏模量值。重要的是，微球的添加改善了材料的载药能力和植物提取物的释放性能，使其成为生物医学、皮肤病学或美容应用的有前景的载体。

    • 胶原基质中的PMMA微球： Polymethylmethacrylate (PMMA) 微球，如Artecoll，通常悬浮在胶原凝胶基质中用作软组织填充剂。PMMA微球本身是不可降解的，其作用机制是通过刺激宿主组织形成胶原，从而达到永久性填充的效果。一项为期5年的研究表明，这种PMMA填充剂在鼻唇沟矫正方面显示出持续改善和纠正的持久性，且没有报告严重的意外设备相关不良事件。

  2. 微球材料对胶原再生的影响

    • PLLA微球的特性： 聚L-乳酸（PLLA）微球因其生物相容性、可降解性以及作为胶原刺激剂的能力而被广泛应用于医美和再生医学。PLLA微球的材料特性，如分子量、化学组成、亲疏水性、尺寸、形态和降解行为，对其诱导胶原再生和异物反应有显著影响。中等分子量和降解速率的PLLA微球（固有粘度为3.80）能强烈再生I型和III型胶原，以维持长期的美学效果。

    • 多孔PLLA微球： 多孔PLLA微球的结构修饰被证明可以加速其作用起效，并减少结节形成。与传统PLLA相比，多孔PLLA微球组在第2周就能观察到胶原沉积，具有更快的起效、增强的炎症细胞浸润、更均匀的组织分布以及显著更少的微聚集体。这种设计通过促进胶原纤维的“穿透生长”来增强填充效果。

    • PLLA-b-PEG微球： 将短链亲水性聚乙二醇（PEG）链引入PLLA分子中，可以改善微球的形态并增强表面亲水性。PLLA-b-PEG微球显示出比纯PLLA微球更好的生物相容性，同时不降低胶原再生能力。

    • PLLA-γ-PGA微球： 聚(γ-谷氨酸)增稠的PLLA微球配方（PLLA-γ-PGA）在老年小鼠模型中显著增强了真皮成纤维细胞的活化，促进了持续的组织重塑，并引发了更轻微的炎症反应，且没有观察到不良反应，优于市售的透明质酸（HA）填充剂和PLLA-羧甲基纤维素钠（PLLA-CMC）配方。这表明PLLA-γ-PGA是一种安全有效的再生材料，具有长期皮肤嫩肤的潜力。

    • PLA-IC（包含维生素C和谷胱甘肽的PLLA填充剂）： 一项研究评估了一种将乙基抗坏血酸（维生素C）和谷胱甘肽稳定在InCube微点阵中的聚乳酸（PLA）填充剂（PLA-IC）。微点阵封装将维生素C和谷胱甘肽保存了277天，并保持了强大的DPPH自由基清除活性长达200天。体内研究显示，PLA-IC在第4至12周表现出比标准PLA填充剂显著更大的增容效果。Masson三色染色显示PLA-IC组的胶原密度更高，在12周时几乎是传统PLA的两倍。H&E切片显示PLA-IC处理的组织炎症浸润减少，新血管形成最小。这表明微点阵封装的维生素C和谷胱甘肽增强了PLA填充剂的抗氧化稳定性以及整体生物刺激性能，带来了更好的体积保持、胶原形成增加和更受控的组织反应。

    • PCL微球： 聚己内酯（PCL）微球被证明能增强脂肪间隔的再生和沉积，促进皮下脂肪组织中I型和III型胶原以及弹性蛋白的合成，并且这种反应是年龄独立的。PCL基填充剂在刺激胶原纤维形成方面有效，主要在脂肪细胞间的间隙中，并通过qPCR分析在基因水平上得到证实。

    • HA/CaHa混合填充剂： HArmonyCa™是一种结合了HA和CaHa微球（25-45 µm）的混合填充剂。它已显示出增容、提升和紧致皮肤的效果，并能增加皮肤的丰满度、弹性和紧实度，暗示着新胶原的形成，使其适用于治疗光老化等病症。这项研究将其用于治疗痤疮后疤痕，取得了显著的皮肤质地改善，阴影效应减少，组织弹性恢复，患者满意度高。

    • PVA/HA填充剂： 一种新型的交联透明质酸凝胶与聚乙烯醇微球（PVA/HA填充剂）结合的填充剂被开发出来，并在大鼠模型中进行了评估。研究发现PVA/HA填充剂具有优异的结构支撑，在6个月观察期内没有显著的形态变化。值得注意的是，该填充剂有效促进了骨膜血管生成，增强了胶原和弹性纤维的增殖。此外，即使在PVA/HA配方中微球浓度增加，它也能保持较低的炎症反应，具有高安全性，并且没有增生的风险。

  3. 微球制备方法与特性

    • 乳化/交联法： 微球的制备通常通过乳化/交联方法进行。这种方法可以制备出具有特定形状和分散性的微球。
    • 调控交联度： 通过调控胶原的交联度，可以获得不同溶解度的胶原基质，从而适用于不同的应用。
    • 包埋活性物质： 压粒技术（prilling technique）可以生产由不同交联度的胶原基质组成的微球，这些微球可以包埋不溶性或亲脂性活性物质，以实现缓释和特定功效。

二、 胶原包入微球在医美中的应用

  1. 皱纹矫正和面部填充：

    • 可注射的皮下填充剂主要用于矫正皮肤皱纹。胶原@PLLA复合填充剂可实现显著的胶原再生，维持长期的填充效果，解决皱纹问题。
    • HA/胶原复合水凝胶填充剂，结合多孔PLLA微球，能够提供即时和持久的填充效果，通过刺激胶原再生来填充面部凹陷并抚平皱纹。
    • PMMA微球填充剂，如Artecoll，被广泛用于面部软组织增容，包括鼻唇沟、唇部、痤疮疤痕等，以实现永久性矫正。

  2. 皮肤再生与抗衰老：

    • PLLA微球通过诱导I型和III型胶原再生来达到长期美学效果。
    • PLLA-γ-PGA配方能显著增强真皮成纤维细胞活化，促进持续的组织重塑，为长期皮肤嫩肤提供了有力的临床前证据。
    • PLA-IC填充剂（包含维生素C和谷胱甘肽的PLLA）通过增强胶原形成和改善体积保持，对美学应用具有潜在优势，有望实现更优越的胶原诱导和组织反应。
    • PCL基填充剂通过增强脂肪间隔的再生和沉积，促进皮下脂肪层胶原和弹性蛋白的合成，可以用于年轻化皮下脂肪组织，增强皮肤体积和弹性。

  3. 疤痕治疗：

    • HA/CaHa混合填充剂（HArmonyCa™）已被用于治疗痤疮后疤痕，通过其增容、提升和刺激新胶原形成的作用，显著改善皮肤质地和恢复组织弹性。
    • PMMA微球填充剂也用于治疗痤疮疤痕。

  4. 生物相容性与安全性：

    • Col@PLLA复合填充剂经过体内外研究验证，具有良好的安全性和成纤维细胞亲和力。
    • PLLA-γ-PGA在老年小鼠模型中显示出更轻微的炎症反应，且没有观察到不良副作用，优于市售HA填充剂和PLLA-CMC配方。
    • PLA-IC填充剂显示出更受控的组织反应和减少的炎症浸润。
    • PLLA-b-PEG微球通过亲水性PEG链的引入，提高了生物相容性，且不影响胶原再生能力。
    • PLLA多孔微球通过结构修饰，减少了结节形成这一PLLA填充剂常见的副作用。
    • PVA/HA填充剂在促进胶原纤维形成的同时，保持了最小的炎症反应，具有高安全性，且无增生风险。
    • 然而，也有报道指出胶原和Plexiglas微球注射后出现脂膜炎的罕见病例。永久性填充剂如PMMA微球，应谨慎用于美容手术，更推荐用于重建手术，且必须强制记录和报告所有不良反应。血管内注射聚-D,L-乳酸与透明质酸（PDLLA-HA）填充剂可能导致罕见但毁灭性的视力障碍和失明并发症，因此需要专家共识来制定安全注射技术和管理算法。PMMA微球也可能导致小血管微栓塞和急性肾小球肾炎，尤其是在注射部位感染后，尽管PMMA被认为不会全身播散，但组织坏死可能有利于微球的全身播散。

三、 挑战与未来方向

尽管胶原包入微球技术取得了显著进展，但仍存在一些挑战和未来的发展方向：

  1. 优化胶原再生速度和持久性： 尽管Col@PLLA和多孔PLLA微球已显示出加速胶原再生的潜力，但仍需进一步研究以优化其再生动力学和长期稳定性，以达到即时且持久的效果。
  2. 减少不良反应： 虽然许多新型微球设计旨在降低炎症反应和结节形成，但像PMMA微球和PDLLA-HA等填充剂仍然存在罕见但严重的并发症风险，如脂膜炎、微栓塞和视力障碍。未来的研究需要进一步提高填充剂的生物安全性，并建立更完善的风险管理和并发症处理方案。
  3. 个性化治疗： 不同的患者可能对填充剂有不同的反应，开发能够根据个体需求调整胶原再生速率和效果的个性化填充剂是未来的一个方向。
  4. 多功能一体化填充剂： 结合多种生物活性成分（如维生素C、谷胱甘肽、TXA）的微球填充剂具有巨大的潜力，可以同时提供胶原再生、抗氧化、美白等多重功效。未来可探索更多此类多功能填充剂的开发。
  5. 长期临床证据： 虽然一些研究提供了长达5年的随访数据，但对于许多新型材料，仍需要大规模、长期的临床试验来充分评估其安全性和有效性。

总之，将胶原包入微球的策略为医美领域带来了显著的进步，通过优化材料组成、结构和释放机制，实现了更快速、更持久、更安全的胶原再生和美学效果。随着生物材料科学和组织工程技术的发展，胶原包入微球在未来将继续为皮肤年轻化和软组织修复提供更多创新和个性化的解决方案。

References

1Engineered collagen/PLLA composite fillers to induce rapid and long-term collagen regeneration.PubMed

Shuhua Chang, Miaoran Zhao, Wenxia Gao, et al.
J Mater Chem B. 2025 Jan 15;13(3):904-917. doi: 10.1039/d4tb02159b.
Injectable subcutaneous fillers are used in medical aesthetics primarily to correct skin wrinkles. The limitations of collagen fillers include rapid degradation, lack of collagen regeneration effects and high-frequency injections. The regenerative filler of Sculptra (Aesthetic) offers prolonged regenerative effects; however, the slow collagen regeneration results in prolonged waiting time for the filling effects. Herein, we report a facile strategy to fabricate dermal fillers with rapid collagen regeneration. Crosslinked collagen was swollen in a weak acidic solution and coated onto the surface of poly(L-lactic acid) (PLLA) microspheres. The collagen@PLLA composite microspheres (Col@PLLA) were dispersed in an aqueous solution of sodium carboxymethyl cellulose (CMC) to form a porous sponge after lyophilization. studies verified the good safety and fibroblast affinity of the Col@PLLA fillers. The fillers were subcutaneously injected to evaluate the effects of collagen regeneration . Compared to the single collagen and PLLA microspheres, the Col@PLLA composite fillers showed significant collagen regeneration after injecting for 5 days. The regenerated type III and type I collagens of Col@PLLA maintained high levels after 4 months post-implantation. The inflammation response further validated the regenerative mechanism and long-lasting potential of this product. The Col@PLLA fillers achieved a significant enhancement in collagen regeneration.

2Porous PLLA microspheres dispersed in HA/collagen hydrogel as injectable facial fillers to enhance aesthetic effects.PubMed

Miaoran Zhao, Shuhua Chang, Yunpeng Wang, et al.
Regen Biomater. 2025 May 23;12:rbaf049. doi: 10.1093/rb/rbaf049. eCollection 2025.
Injectable facial fillers such as Sculptra stimulate collagen regeneration to fill wrinkles; however, the collagen regeneration is not satisfactory due to the slow emergence of filling effect. In this study, we designed a regenerative dermal filler to provide both immediate and long-lasting filling effects. A hydrogel matrix composed of crosslinked hyaluronic acid (HA) and collagen was engineered to encapsulate porous poly(L-lactide) (PLLA) microspheres and tranexamic acid (TXA). The hydrogel matrix was administered via intradermal injection to achieve wrinkle filling. TXA is released to exert skin-whitening effects, while the porous PLLA microspheres and their degradation product, lactic acid, continuously stimulate collagen regeneration over an extended period. Facial volume increased immediately following hydrogel injection. Large amounts of new Type I and Type III collagen are generated. The porous structure of PLLA microspheres facilitated the 'penetrating growth' of collagen fibers, which effectively filled facial depressions and smoothed wrinkles. Overall, the HA/collagen composite hydrogel filler exhibited excellent esthetic effects.

3Collagen/Gelatin/Hydroxyethyl Cellulose Composites Containing Microspheres Based on Collagen and Gelatin: Design and Evaluation.PubMed

Justyna Kozlowska, Natalia Stachowiak, Alina Sionkowska
Polymers (Basel). 2018 Apr 19;10(4):456. doi: 10.3390/polym10040456.
The objective of this study was to develop three-dimensional collagen/gelatin/hydroxyethyl cellulose composites in combination with gelatin or collagen-gelatin loaded microspheres. Microspheres were prepared by an emulsification/crosslinking method. A 1-Ethyl3-(3dimethyl-aminopropyl)-carbodiimide (EDC) and -hydroxysuccinimide (NHS) mixture were used as a crosslinking agent for the obtained materials. The structure of the materials was studied using scanning electron microscopy (SEM) and infrared spectroscopy. Moreover, a (pot marigold) flower extract release profile of the microsphere-loaded matrices was assessed in vitro. Additionally, porosity, density, stability, swelling and mechanical properties were tested. On the basis of SEM images, the microspheres exhibited a spherical shape and were irregularly dispersed in the polymer matrix. However, it was found that the addition of microparticles to obtained materials did not significantly change their microstructure. We observed a slight decrease in the swelling properties of matrices and an increase in values of Young's modulus. Significantly, the addition of microspheres to the polymer matrices led to improved loading capacity of materials and release performance of flower extract. This makes the collagen/gelatin/hydroxyethyl cellulose composites containing microspheres a promising and suitable vehicle for biomedical, dermatological, or cosmetic applications.

4inducing collagen regeneration of biodegradable polymer microspheres.PubMed

Yixin Zhang, Hanwen Liang, Qian Luo, et al.
Regen Biomater. 2021 Jul 15;8(5):rbab042. doi: 10.1093/rb/rbab042. eCollection 2021 Oct.
Biodegradable polymer particles have been used as dermal fillers for pre-clinical and clinical trials. The impact of material properties of polymers is very important to develop products for aesthetic medicine such as dermal fillers. Herein, eight biodegradable polymers with different molecular weights, chemical compositions or hydrophilic-hydrophobic properties were prepared and characterized for systematical study for aesthetic medicine applications. Polymer microspheres with 20-100 μm were prepared. The degradation study showed that poly (L-lactic--glycolic acid) 75/25 microspheres degraded the fastest, whereas poly (L-lactic acid) (PLLA) microspheres with intrinsic viscosity of 6.89 ([] = 6.89) with the highest molecular weight showed the slowest degradation rate. After these microspheres were fabricated dermal fillers according to the formula of Sculptra, they were injected subcutaneously into the back skin of rabbits. results demonstrated that the degradation rate of microspheres strongly correlated with the foreign body reaction and collagen regeneration was induced by microspheres. The microspheres with faster degradation rate induced inflammatory response and the collagen regeneration maintained in shorter time. PLLA ([] = 3.80) microsphere with a moderate molecular weight and degradation rate could strongly regenerate Type I and III collagen to maintain a long-term aesthetic medicine effect. These properties of size, morphology and degradation behavior would influence the foreign body reaction and collagen regeneration.

5Poly-lactic Acid Dermal Filler Enriched With InCube-encapsulated Vitamin C and Glutathione: Preclinical Evidence of Superior Collagen Induction and Tissue Response Compared With Conventional PLA.PubMed

Jinyoung Jang, Caijun Jin, Zhiyuan Ding, et al.
In Vivo. 2026 Mar-Apr;40(2):933-945. doi: 10.21873/invivo.14249.
BACKGROUND/AIM: Poly-Lactic acid (PLA) fillers are widely used for facial and body volume restoration because of their collagen-stimulating properties. However, early inflammation, oxidative stress, and variable long-term remodeling remain as concerns. Vitamin C and glutathione support collagen synthesis and redox homeostasis but degrade rapidly in conventional systems. This study evaluated a PLA filler incorporating Ethyl ascorbic acid (Vitamin C) and glutathione stabilized within an InCube microlattice (PLA-IC) focusing on antioxidant stability, collagen induction, and tissue response. MATERIALS AND METHODS: PLA-IC were prepared by combining PLA microspheres with microlattice-encapsulated vitamin C and glutathione. Scanning and transmission electron microscopy and selected-area electron diffraction were used to characterize particle morphology and structure. Antioxidant stability was examined using high-performance liquid chromatography and DPPH radical-scavenging assays during long-term storage. , SKH mice received subcutaneous injections of PBS, commercial PLA filler, or PLA-IC. Surface volume changes were measured by Primos imaging, and histology was used to assess inflammation, neovascularisation, and collagen deposition over 12 weeks. RESULTS: Microlattice encapsulation preserved vitamin C and glutathione for 277 days and maintained strong DPPH-scavenging activity for up to 200 days. , PLA-IC showed significantly greater volumizing effect than standard PLA filler between weeks 4 and 12. Masson's trichrome staining demonstrated higher collagen density in the PLA-IC group, reaching nearly twice that of conventional PLA at 12 weeks. H&E sections revealed reduced inflammatory infiltration and minimal neovascularisation in PLA-IC-treated tissues. CONCLUSION: Microlattice-based incorporation of vitamin C and glutathione enhances the antioxidants stability and overall biostimulatory performance of PLA filler. Compared with conventional PLA, PLA-IC demonstrated improved volume retention, increased collagen formation, and a more controlled tissue response, indicating potential advantages for aesthetic applications and warranting clinical evaluation of safety and efficacy.

6Poly(γ-glutamic acid)-thickened PLLA microspheres with enhanced biocompatibility and efficacy in aged mice.PubMed

Dan-Qi Ren, Hui-Zhen Peng, Yue Zhang, et al.
J Mater Chem B. 2026 Feb 25. doi: 10.1039/d5tb02761f.
Poly(L-lactic acid) (PLLA) microspheres are widely used in aesthetic and regenerative medicine to promote collagen remodeling, but their efficacy and long-term safety lack sufficient experimental data. In this study, a poly(γ-glutamic acid)-thickened PLLA microsphere formulation (PLLA-γ-PGA) was developed, and its biocompatibility and efficacy were evaluated in an aged mice model induced by subcutaneous injection of D-galactose combined with UV irradiation. As a result, PLLA-γ-PGA significantly enhanced dermal fibroblast activation, promoted sustained tissue remodeling and elicited milder inflammatory responses without observable adverse effects, outperforming marketed hyaluronic acid (HA) fillers and PLLA-carboxymethyl cellulose sodium (PLLA-CMC) formulations. These findings present PLLA-γ-PGA as a safe and efficacious regenerative material, providing robust preclinical evidence to support its translational potential for long-term skin rejuvenation.

7Panniculitis induced by collagen and plexiglas microsphere injections used for aesthetic treatment.PubMed

D Biasi, P Caramaschi, A Carletto, et al.
Clin Rheumatol. 1999;18(4):328-9. doi: 10.1007/s100670050110.
The authors report an unusual case characterised by the prompt appearance of panniculitis after injections of collagen and plexiglas microsphere for aesthetic aim and review the literature about aesthetic treatments and rheumatic disorders.

8[Collagen and its technological possibilities].PubMed

J Cotte, H Dumas
J Pharm Belg. 1991 May-Jun;46(3):201-10.
Collagen enjoys a privileged position as a biomaterial in its cosmetic applications. It exists under different forms and is more particularly able to reticulate. The process which is used allows a modulated reticulation. This means that a collagenous matrix having a varying degree of solubility can be obtained, which can lend itself to different applications. The prilling technique consists in producing microspheres consisting of a more or less reticulated collagenous matrix being able or not to imprison an insoluble or lipophilic active substance having previously been incorporated in the original solution. In this way, it is possible to obtain either strongly reticulated and mechanically resistant microspheres of particles which dissolve when crushed. The cosmetic significance of these new products is connected with the biocompatibility characteristics of the collagenous material and with the characteristics relating to the modulated reticulation of the obtained product.

9Modification of Collagen/Gelatin/Hydroxyethyl Cellulose-Based Materials by Addition of Herbal Extract-Loaded Microspheres Made from Gellan Gum and Xanthan Gum.PubMed

Justyna Kozlowska, Weronika Prus-Walendziak, Natalia Stachowiak, et al.
Materials (Basel). 2020 Aug 8;13(16):3507. doi: 10.3390/ma13163507.
Because consumers are nowadays focused on their health and appearance, natural ingredients and their novel delivery systems are one of the most developing fields of pharmacy, medicine, and cosmetics. The main goal of this study was to design, prepare, and characterize composite materials obtained by incorporation of microspheres into the porous polymer materials consisting of collagen, gelatin, and hydroxyethyl cellulose. Microspheres, based on gellan gum and xanthan gum with encapsulated flower extract, were produced by two methods: extrusion and emulsification. The release profile of the extract from both types of microspheres was compared. Then, obtained microparticles were incorporated into polymeric materials with a porous structure. This modification had an influence on porosity, density, swelling properties, mechanical properties, and stability of materials. Besides, in vitro tests were performed using mouse fibroblasts. Cell viability was assessed with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The obtained materials, especially with microspheres prepared by emulsion method, can be potentially helpful when designing cosmetic forms because they were made from safely for skin ingredients used in this industry and the herbal extract was successfully encapsulated into microparticles.

10Comparison of Different Types of Poly-L-Lactic Acid Microspheres In Vitro and In Vivo Studies.PubMed

Ruilin Liu, Tong He, Ruizhi Li, et al.
Aesthet Surg J Open Forum. 2024 Oct 22;6:ojae091. doi: 10.1093/asjof/ojae091. eCollection 2024.
BACKGROUND: Biodegradable polymers are commonly used as dermal fillers in plastic surgery. Among these, poly-L-lactic acid (PLLA) distinguishes itself owing to its good biocompatibility, degradability, and ability to act as a collagen stimulator. OBJECTIVES: In this study, the differential behavior of PLLA microspheres with varying microscopic morphology and surface hydrophilicity was investigated both in vitro and in vivo. METHODS: The introduction of short hydrophilic polyethylene glycol (PEG) chains into the PLLA molecule was employed to modify the morphology and enhance the surface hydrophilicity of the microspheres. The morphology and physicochemical properties of the PLLA and PLLA-b-PEG microspheres were characterized. Irregular PLLA particles, PLLA, and PLLA-b-PEG microspheres were implanted into the subcutaneous tissue of rabbit models, and at 4, 26, and 52 weeks after implantation, biopsy samples were collected for hematoxylin and eosin and Masson's trichrome staining to evaluate differences in the tissue response between different implants. RESULTS: The results of in vitro research demonstrated that while the addition of short-chain hydrophilic PEG afforded a smoother surface for the microspheres, it had no significant effect on the molecular weight and degradation rate of PLLA. The histological examination revealed that the PLLA-b-PEG microspheres exhibited enhanced biocompatibility compared with the pure PLLA microspheres, while the irregular PLLA particles showed the highest inflammatory response among the 3 materials. CONCLUSIONS: In this study, we found that the properties of PLLA were improved upon modification by short-chain PEG without reducing the collagen regeneration ability, thereby affording a better histocompatibility.

11Enhancement of Fat Septa: Polycaprolactone (PCL) Microspheres Boost Collagen Production in Subcutaneous Adipose Tissue.PubMed

Shuo Liu, Yongshu Wang, Eric Gao, et al.
Aesthet Surg J. 2025 Apr 16;45(5):514-524. doi: 10.1093/asj/sjaf001.
BACKGROUND: The reduction in collagen content within the subcutaneous fat layer due to aging results in thinning and weakening of the fibrous septum, leading to an unstable fat pad. Studies on the mechanism of action of polycaprolactone (PCL) collagen stimulators in the adipose layer are lacking. OBJECTIVES: This research aimed to explore the effectiveness of PCL-based filler in enhancing the fibrous septum within adipose tissue, thereby facilitating collagen and elastin synthesis in the adipose layer, while also comparing the disparities in the process between juvenile and aged individuals. METHODS: A rat model was utilized to study subcutaneous fat implantation effects of PCL-based filler. Over 4 months, the impact on fibrous septum formation was evaluated with Masson's trichrome staining and immunostainings for Types I and III collagen, and a structural evaluation through scanning electron microscopy analysis. PCL-induced collagenization mechanisms were explored by quantitative polymerase chain reaction (qPCR). Elastin regeneration was examined with Elastica van Gieson (EVG) staining. RESULTS: Histological analysis demonstrated that PCL-based filler effectively stimulated collagen fiber formation in subcutaneous adipose tissue in both juvenile and aged rats. Immunostainings indicated significant promotion of Types I and III collagen regeneration, primarily within the interstitial spaces among adipocytes, as well as its confirmation at the genetic level through qPCR analysis. EVG staining further unveiled the role of PCL in promoting elastin production while mitigating age-related decline. CONCLUSIONS: PCL-based filler enhanced fat septum regeneration and deposition, demonstrating a robust, age-independent response. These findings suggest PCL-based fillers as promising therapeutic agents for rejuvenating subcutaneous adipose tissue and enhancing skin volume and elasticity in cosmetic and reconstructive contexts.

12Minimally Invasive Post-Acne Scars Treatment with the Hybrid Filler HArmonyCa™.PubMed

Mauro Barone, Riccardo De Bernardis, Paolo Persichetti
Aesthetic Plast Surg. 2025 Apr;49(7):2134-2136. doi: 10.1007/s00266-024-04046-6. Epub 2024 May 6.
Acne, a chronic inflammatory condition of the pilo-sebaceous unit, often results in scarring with significant aesthetic and psychological consequences for patients. While various treatments exist, including surgical and non-surgical approaches, a combined method has shown promise in effectively addressing acne scarring. Lipofilling, with its adipose-derived stem cells, has emerged as a promising technique for volume restoration and collagen stimulation but may not be suitable for all patients, especially those who prefer non-surgical treatments. Recently, a novel approach involving simultaneous injection of hyaluronic acid (HA) and calcium hydroxyapatite (CaHa) has been introduced in the literature, showing lifting properties, improving dermal thickness and skin texture, and inducing neocollagenesis. HArmonyCa™ (Allergan Aesthetics, an AbbVie Company) is a hybrid filler combining HA (20 mg/mL) and CaHa 55.7% (microspheres 25-45 µm) with 0.3% lidocaine in a 1.25-ml syringe. It has demonstrated volumizing, lifting, and skin-tightening effects, along with increased fullness, elasticity, and turgor of the skin. It has also shown an increase in viscoelasticity, suggesting new collagen formation, making it suitable for treating conditions like solar elastosis. Compared to lipofilling, HArmonyCa™ offers a non-surgical alternative with comparable outcomes and patient satisfaction. These findings have led us to employ this hybrid filler for the treatment of post-acne scarring. We present a case of a 35-year-old woman with post-acne scarring, treated with HArmonyCa™ combined with Volite™ injections, CO laser resurfacing, and chemical peels. Significant improvement in skin texture, reduction of shadowing effect, and restoration of tissue elasticity were observed, resulting in high patient satisfaction. While HArmonyCa™ presents a promising solution for post-acne scarring, further research is needed to comprehensively evaluate its efficacy and suitability. This study contributes to the growing body of literature exploring the potential applications of hybrid fillers, particularly in addressing post-acne scarring.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

13Plasma gel as a new augmentation material for injection laryngoplasty in rabbit model: histologic analysis.PubMed

Seok Jin Hong, Sang Hyuk Lee, Sung Min Jin, et al.
Otolaryngol Head Neck Surg. 2013 Oct;149(4):596-602. doi: 10.1177/0194599813495664. Epub 2013 Jul 11.
OBJECTIVES: Currently, a variety of materials are available for the treatment of glottal insufficiency. Ideal injection materials should be inexpensive, easily obtainable, nontoxic, and biocompatible. Plasma gel has recently been developed as an injectable, autologous material used in plastic surgery. The aim of this study was to evaluate the histological changes in rabbit vocal folds (VFs) after an injection of plasma gel, compared with collagen (Artecoll) or hyaluronic acid (Reviderm Intra). STUDY DESIGN: Experimental prospective animal study. SETTING: Animal laboratory. SUBJECTS AND METHODS: Blood samples were collected from 12 New Zealand rabbits. Plasma collected from each rabbit was centrifuged and processed using a gel heating system. All rabbits received a 0.05 ml injection of plasma gel into the right VF, while an equivalent volume of Artecoll or Reviderm Intra was injected into the left VFs of each 6 rabbits randomly. The larynges were collected 2, 4, and 8 weeks after injection, and the tissues were stained for histological analysis. RESULTS: In comparison with left VFs injected with Artecoll or Reviderm Intra, there was significantly less inflammatory response and foreign body reaction in the plasma gel injected right VFs (P < .05). Multinucleated foreign body type giant cells were also more prevalent in the left VFs. There were no quantitative differences in the rates of neovascularization or collagen deposition between groups. CONCLUSION: Plasma gel is a biologically compatible material that may serve as a suitable augmentation material in injection laryngoplasty. Further studies that examine the long-term effects in a larger number of subjects are needed.

14Surgery for foreign body reactions due to injectable fillers.PubMed

Dolores Wolfram, Alexandar Tzankov, Hildegunde Piza-Katzer
Dermatology. 2006;213(4):300-4. doi: 10.1159/000096193.
BACKGROUND: An increasing number of soft tissue fillers have been introduced to the beauty market and these filler substances are widely used as non-toxic, non-immunogenic and relatively harmless injectable alternatives to surgical rejuvenation. Generally, facial fillers are injectable - or surgically insertable - products that are used to fill up the volume loss in the aging face. Depending on bioavailability, chemical composition and degradation, fillers can be classified as temporary or permanent, organic or inorganic and autologous or heterologous. OBJECTIVE: A plethora of new products has swamped the beauty market since face rejuvenation has become socially acceptable as well as affordable to a wider population, but adverse reactions cannot be excluded. We present 4 patients with complications after injection of facial fillers [including Artecoll(polymethylmethacrylate microspheres), Restylane (hyaluronic acid), DermaLive (hyaluronic acid plus acrylic hydrogel particles) and Newfill (polylactic acid)] and surgical correction. RESULTS: Surgical intervention led to good aesthetic and functional results after multiple unsuccessful conservative therapies. CONCLUSION: We recommend that only physicians familiar with the injection techniques and the biological and chemical characteristics of the various injectable products should perform such interventions. Especially permanent fillers should be used with utmost reticence in cosmetic surgery and we would recommend their application only in reconstructive procedures. Additionally, documentation and reporting of all adverse effects must be mandatory.

15Small vessel microembolization and acute glomerulonephritis following infection of aesthetic filler implants.PubMed

Pablo Cannata-Ortiz, Carolina Gracia, Youssef Aouad, et al.
Diagn Pathol. 2016 Jan 8;11:2. doi: 10.1186/s13000-016-0453-y.
BACKGROUND: The systemic consequences of esthetic filler injections are poorly understood. CASE PRESENTATION: We report a patient with a past history of subcutaneous injection of aesthetic filler material in the lower legs, who presented with post-infectious glomerulonephritis following necrotic leg ulcers at the injection site. Kidney biopsy revealed the presence of translucent, non-birefringent microspherical bodies compatible with polymethylmetacrylate (PMMA) microspheres in some capillary lumens. This had not previously been described. PMMA is a biphasic aesthetical filler composed of polymethylmetacrylate microspheres suspended in a biodegradable bovine collagen carrier. The solid phase (PMMA microspheres) persists in tissues for years. Although PMMA was thought to not disseminate systemically, tissue necrosis may have favored systemic dissemination of the microspheres, although entry in the circulation and microembolization at the time of administration cannot be ruled out. CONCLUSIONS: In conclusion, aesthetic filler implants may cause microembolization into small vessels. Recognition of the characteristic morphology may expedite diagnosis and avoid unnecessary further testing.

16Clinical experience with polymethylmethacrylate microspheres (Artecoll) for soft-tissue augmentation: a retrospective review.PubMed

Amita Bagal, Ravi Dahiya, Vance Tsai, et al.
Arch Facial Plast Surg. 2007 Jul-Aug;9(4):275-80. doi: 10.1001/archfaci.9.4.275.
OBJECTIVE: To evaluate patient satisfaction and clinical outcomes with soft-tissue augmentation using an injectable alloplast composed of polymethylmethacrylate microspheres 30 to 40 microm in diameter suspended in atelocollagen (3.5% collagen solution) (Artecoll; Artes Medical Inc, San Diego, California). DESIGN: A retrospective review of the literature and an evaluation of our clinical experience with Artecoll implantation for facial soft-tissue augmentation were performed. In a large private metropolitan clinical facial plastic surgery practice, 72 patients (62 females and 10 males) underwent Artecoll implantation between January 1, 1997, and June 30, 2002. Artecoll was implanted into different facial sites, including the philtrum, acne scars, corners of the mouth, upper and lower lips, melolabial folds (also known as nasolabial folds), and other facial creases to attain permanent soft-tissue augmentation. Via completion of an anonymous survey, patients performed subjective evaluation of the aesthetic results. Subjective evaluation of aesthetic results by the surgeon was based on review of photographic documentation. Objective variables, including complications, sites most often treated, total number of treatments, and volume of implant material injected, were obtained by reviewing patient medical records. RESULTS: Among 72 patients, 40 returned a completed patient satisfaction survey (56% response rate). The most common reason cited by patients (35 of 40) for selecting Artecoll implantation was that the implantation offered permanent correction. Five of 40 patients reported persistent problems with Artecoll (firmness of the lip in 1 patient, increased sensitivity of the lip for 6 months in 1 patient, and lumps in their lips in 3 patients). Eighty-five percent of patients (34 of 40) reported that the treatment met or exceeded their expectations, 13% (5 of 40) reported that the treatment was less satisfying than expected, and 3% (1 of 40) reported that the treatment was much less satisfying than expected. Ninety-five percent (38 of 40) reported that they would recommend Artecoll implantation to a friend or relative, and 90% (36 of 40) reported that they would undergo Artecoll implantation again. The retrospective medical record review revealed that the most commonly requested facial areas for augmentation were (in order of frequency) upper lip, lower lip, melolabial folds, corners of the mouth, and other facial creases. Seventy-two patients underwent 177 Artecoll implantation procedures. The mean number of treatments required to obtain favorable soft-tissue augmentation was 2.4. The medical record review confirmed that 5 of 72 patients had complications after Artecoll implantation (nodule formation in 4 patients and persistent lip pain in 1 patient). Sixty-two of 72 patients (86%) achieved favorable soft-tissue augmentation with a total Artecoll implant volume of 3.0 mL or less. CONCLUSIONS: Artecoll is a satisfying treatment for lip augmentation or for treatment of facial creases and furrows among patients seeking permanent correction. However, implantation success is technique sensitive. Conservative gradual implantation provides favorable results and few complications. Implantation in the subdermal plane is critical to obtain favorable outcomes using this injectable alloplast.

17Consensus Opinion on Safe Injection Technique and Management of PDLLA-HA200-Induced Visual Impairment.PubMed

Kian Hong Edmond Lau, Stephanie Young, Alice Goh, et al.
J Craniofac Surg. 2025 Dec 8. doi: 10.1097/SCS.0000000000012271.
Poly-D,L-lactic acid with hyaluronic acid (PDLLA-HA) represents a next-generation injectable combining the collagen-stimulating property of poly-D,L-lactic acid (PDLLA) microspheres with non-cross-linked hyaluronic acid (HA) as a carrier. One rare but devastating complication is visual field impairment and blindness due to inadvertent intravascular injection. Recognizing the need for a dedicated consensus on the management of PDLLA-HA-induced visual impairment, a panel of experts comprising oculoplastic surgeons, dermatologists, and aesthetic physicians was convened to give a consensus on safe practice with PDLLA-HA 200 (Juvelook Volume/Lenisna) and develop a management algorithm for the management of PDLLA-HA-induced blindness.

18Five-year safety and efficacy of a novel polymethylmethacrylate aesthetic soft tissue filler for the correction of nasolabial folds.PubMed

Steven R Cohen, Carl F Berner, Mariano Busso, et al.
Dermatol Surg. 2007 Dec;33 Suppl 2:S222-30. doi: 10.1111/j.1524-4725.2007.33365.x.
BACKGROUND: A novel soft tissue filler composed of polymethylmethacrylate (PMMA) microspheres suspended in a collagen gel matrix containing 0.3% lidocaine (ArteFill, Artes Medical, Inc.) was recently approved by the Food and Drug Administration for the correction of nasolabial folds. A randomized, multicenter, controlled pivotal trial performed in the United States established the safety and efficacy of this medical device throughout a 12-month study period. OBJECTIVE: The objective was to substantiate the long-term 5-year safety and efficacy of this novel soft tissue PMMA filler. METHODS AND MATERIALS: Attempts were made to contact all subjects treated with the PMMA filler that were enrolled in the original pivotal study. Safety was assessed by standard adverse event reporting methods. Efficacy was determined using a validated six-point facial fold assessment photometric grading scale using blinded observers' assessment of standardized photographs. RESULTS: Subjects (n=119) demonstrated significant improvement in nasolabial folds comparing baseline (before any treatment) to 5 years after their last treatment (p<.001). Notably, subjects also demonstrated continued improvement between 6 months after their last treatment and Year 5 (p=.002). No serious unanticipated device-related adverse events were reported. CONCLUSION: This PMMA filler is the first soft tissue filler to demonstrate continued improvement and persistence of correction over a 5-year period posttreatment.

19A Novel High-Safety Filler with Potential Periosteal Enhancement: In Vivo Evaluation of Cross-Linked Sodium Hyaluronate Gel with PVA Microspheres in Rat Models.PubMed

Yuchen Dai, Xiaowen Liu, Zhen Li, et al.
J Cosmet Dermatol. 2025 Nov;24(11):e70522. doi: 10.1111/jocd.70522.
BACKGROUND: In recent years, the demand for sophisticated aesthetic solutions and the emergence of novel materials in cosmetic dermatology have increased substantially. However, these materials induce marked inflammatory reactions. To address this limitation, in this study, we developed a novel filler Cross-Linked Sodium Hyaluronate Gel combined with Polyvinyl Alcohol Microspheres (PVA/HA filler) and systematically evaluated its effects on the periosteum and subcutaneous tissue in a rat model. METHODS: Ultrasound, histopathology, and molecular biological assays were employed to systematically assess the shape retention of the PVA/HA filler and its biological responses at 1, 3, and 6 months in the periosteum and subcutaneous tissues. RESULTS: Experimental data demonstrated that the PVA/HA filler exhibited excellent structural support, with no significant morphological changes observed over the 6-month observation period. Notably, the filler effectively promoted periosteal angiogenesis and enhanced proliferation of collagen and elastic fibers. Furthermore, it maintained low inflammatory responses, even with increased microsphere concentrations in the PVA/HA formulation. CONCLUSIONS: The novel PVA/HA filler demonstrated strong structural support in both the periosteum and subcutaneous tissue. The filler provides enhanced periosteal angiogenesis, promotes periosteal thickening, and stimulates collagen fiber formation, while exhibiting minimal inflammation, high safety, and no risk of hyperplasia.

20Faster efficacy and reduced nodule occurrence with PLLA (poly-l-lactic acid) porous microspheres.PubMed

Qihua Cao, Jiayu Chen, Zijun Zhang, et al.
Front Bioeng Biotechnol. 2025 Jul 29;13:1571820. doi: 10.3389/fbioe.2025.1571820. eCollection 2025.
INTRODUCTION: Poly-L-lactic acid (PLLA) has gained prominence as an injectable dermal filler as it can both stimulate collagen regeneration and deliver long-lasting effects. However, its application is often hampered by delayed therapeutic onset and adverse events, particularly nodule formation, likely due to uneven distribution caused by the easy formation of small clumps during PLLA reconstitution. METHODS: In this study, PLLA porous microspheres were administered at six dorsal sites on one flank of New Zealand white rabbits, with six contralateral sites receiving Löviselle as control. At predetermined experimental time points, subjects were humanely euthanized. Post-euthanasia, tissue sections underwent histological examination through hematoxylin and eosin (H&E) staining and Masson's trichrome technique, with subsequent statistical analysis of the observational data. RESULTS: The PLLA porous microsphere group demonstrated significantly faster onset of action compared to the control, with observable collagen deposition as early as week 2, enhanced inflammatory cell infiltration, more homogeneous tissue distribution, and substantially fewer microaggregates upon histological examination. DISCUSSION: Structural modification of PLLA microspheres has successfully accelerated their onset of action while reducing nodule formation, thereby providing novel insights for clinical applications.
内容由 AI 生成，仅供参考，请仔细甄别