两种基于羟基磷灰石的真皮填充剂的理化特性和生物刺激功能比较。

Comparison of Physicochemical Characteristics and Biostimulatory Functions in Two Calcium Hydroxyapatite-Based Dermal Fillers.

出版信息

J Drugs Dermatol. 2023 Sep 1;22(9):910-916. doi: 10.36849/JDD.7684.

Abstract

BACKGROUND

Dermal fillers containing calcium hydroxyapatite (CaHA) are categorized as biostimulatory. However, differences in CaHA biomaterial likely affect the resultant induction of collagen synthesis, and variability in microsphere shape and size likely influences a patient’s immune response. This study compares 2 CaHA based fillers: one suspended in carboxymethylcellulose (denoted "CaHA/CMC"), and one crosslinked with 1,4-butanediol diglycidyl ether to hyaluronic acid (denoted "CaHA/HA").

OBJECTIVE

To characterize CaHA/CMC and CaHA/HA fillers to stimulate in vitro collagen biosynthesis.

METHODS

Physicochemical evaluations included G′ and extrusion force. Scanning electron microscopy (SEM) was used to characterize isolated CaHA microspheres and freeze-dried formulations. Collagen I and III expression were evaluated using immunofluorescence.

RESULTS

CaHA/CMC showed higher G′ (P<0.001) and lower extrusion force (P=0.0003), with uniform polymeric-matrix interactions, compared with CaHA/HA. On SEM, isolated microspheres and freeze-dried CaHA/CMC showed round and smooth surfaced microspheres of similar size. Isolated microspheres and freeze-dried CaHA/HA showed nonhomogeneous, broken microspheres, of various sizes, with fragments embedded in the polymer matrix. Although both fillers induced collagen III expression, only CaHA/CMC induced longer-lasting collagen I expression, with increases of 123% (P=0.007) and 164% (P<0.0001) at 2 and 5 mg/mL, respectively, compared with control. CaHA/CMC also increased collagen I expression at equivalent CaHA microsphere concentrations at 2 (P=0.0052) and 5 mg/mL (P<0.0001), compared with CaHA/HA.

CONCLUSION

The physicochemical characteristics selected for evaluation were more favorable for CaHA/CMC than CaHA/HA. When compared with CaHA/HA, the smooth, homogeneous microsphere composition of CaHA/CMC promoted significantly more collagen I biosynthesis, an essential process for tissue augmentation and long-lasting aesthetic improvement. Citation: Kunzler C, Hartmann C, Nowag B, et al. Comparison of physicochemical characteristics and biostimulatory functions in two calcium hydroxyapatite-based dermal fillers. J Drugs Dermatol. 2023;22(9):910-916. doi:10.36849/JDD.7684.

摘要

背景

含羟基磷灰石钙（CaHA）的真皮填充剂被归类为生物刺激剂。然而，CaHA 生物材料的差异可能影响胶原合成的诱导，微球形状和大小的差异可能影响患者的免疫反应。本研究比较了两种基于 CaHA 的填充物：一种悬浮在羧甲基纤维素（表示为“CaHA/CMC”）中，另一种与 1,4-丁二醇二缩水甘油醚交联的透明质酸（表示为“CaHA/HA”）。

目的

为了表征 CaHA/CMC 和 CaHA/HA 填充物以刺激体外胶原蛋白生物合成。

方法

物理化学评估包括 G'和挤出力。扫描电子显微镜（SEM）用于表征分离的 CaHA 微球和冻干制剂。使用免疫荧光法评估 I 型和 III 型胶原蛋白的表达。

结果

与 CaHA/HA 相比，CaHA/CMC 表现出更高的 G'（P<0.001）和更低的挤出力（P=0.0003），具有均匀的聚合物基质相互作用。在 SEM 上，分离的微球和冻干的 CaHA/CMC 显示出相似大小的圆形和光滑表面的微球。分离的微球和冻干的 CaHA/HA 显示出不均匀的、破碎的微球，具有各种大小的碎片嵌入聚合物基质中。尽管两种填充物都诱导了胶原蛋白 III 的表达，但只有 CaHA/CMC 诱导了更持久的胶原蛋白 I 的表达，在 2 和 5mg/mL 时分别增加了 123%（P=0.007）和 164%（P<0.0001），与对照组相比。与 CaHA/HA 相比，CaHA/CMC 还在等效的 CaHA 微球浓度下增加了胶原蛋白 I 的表达，在 2mg/mL（P=0.0052）和 5mg/mL（P<0.0001）时均有增加。