Song Hengyue, Gao Kewa, Hao Dake, Li Andrew, Liu Ruiwu, Anggito Bryan, Yin Boyan, Jin Qianyu, Dartora Vanessa, Lam Kit S, Smith Lucas R, Panitch Alyssa, Zhou Jianda, Farmer Diana L, Wang Aijun
Center for Surgical Bioengineering, Department of Surgery, UC Davis Medical Center, Sacramento, CA, United States.
Department of Burns and Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Front Pharmacol. 2023 Mar 1;14:1125209. doi: 10.3389/fphar.2023.1125209. eCollection 2023.
The lack of vascularization associated with deep burns delays the construction of wound beds, increases the risks of infection, and leads to the formation of hypertrophic scars or disfigurement. To address this challenge, we have fabricated a multi-functional pro-angiogenic molecule by grafting integrin αvβ3 ligand LXW7 and collagen-binding peptide (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY (LDS), and further employed this to functionalize collagen-based Integra scaffolds. Using a large deep burn wound model in C57/BLK6 mice (8-10 weeks old, 26-32g, = 39), we demonstrated that LDS-modified collagen-based Integra scaffolds loaded with endothelial cells (ECs) accelerate wound healing rate, re-epithelialization, vascularization, and collagen deposition. Specifically, a 2 cm × 3 cm full-thickness skin burn wound was created 48 h after the burn, and then wounds were treated with four groups of different dressing scaffolds, including Integra + ECs, Integra + LDS, and Integra + LDS + ECs with Integra-only as the control. Digital photos were taken for wound healing measurement on post-treatment days 1, 7, 14, 21, 28, and 35. Post-treatment photos revealed that treatment with the Intgera + LDS + ECs scaffold exhibited a higher wound healing rate in the proliferation phase. Histology results showed significantly increased re-epithelialization, increased collagen deposition, increased thin and mixed collagen fiber content, increased angiogenesis, and shorter wound length within the Integra + LDS + ECs group at Day 35. On Day 14, the Integra + LDS + ECs group showed the same trend. The relative proportions of collagen changed from Day 14 to Day 35 in the Integra + LDS + ECs and Integra + ECs groups demonstrated decreased thick collagen fiber deposition and greater thin and mixed collagen fiber deposition. LDS-modified Integra scaffolds represent a promising novel treatment to accelerate deep burn wound healing, thereby potentially reducing the morbidity associated with open burn wounds. These scaffolds can also potentially reduce the need for autografting and morbidity in patients with already limited areas of harvestable skin.
深度烧伤所伴随的血管化不足会延迟创面床的构建，增加感染风险，并导致增生性瘢痕的形成或毁容。为应对这一挑战，我们通过将整合素αvβ3配体LXW7和胶原结合肽（SILY）接枝到硫酸皮肤素（DS）糖胺聚糖主链上制备了一种多功能促血管生成分子，命名为LXW7-DS-SILY（LDS），并进一步用其对基于胶原的Integra支架进行功能化处理。利用C57/BLK6小鼠（8 - 10周龄，26 - 32克，n = 39）的大面积深度烧伤创面模型，我们证明负载内皮细胞（ECs）的LDS修饰的基于胶原的Integra支架可加速伤口愈合速度、再上皮化、血管化和胶原沉积。具体而言，在烧伤后48小时创建一个2厘米×3厘米的全层皮肤烧伤创面，然后用四组不同的敷料支架对创面进行处理，包括Integra + ECs、Integra + LDS以及Integra + LDS + ECs，以仅使用Integra作为对照。在治疗后第1、7、14、21、28和35天拍摄数码照片以测量伤口愈合情况。治疗后的照片显示，在增殖期，用Integra + LDS + ECs支架治疗的创面愈合速度更快。组织学结果显示，在第35天时，Integra + LDS + ECs组的再上皮化显著增加、胶原沉积增加、细胶原纤维和混合胶原纤维含量增加、血管生成增加且伤口长度缩短。在第14天时，Integra + LDS + ECs组呈现相同趋势。Integra + LDS + ECs组和Integra + ECs组从第14天到第35天胶原的相对比例变化表明，粗胶原纤维沉积减少，细胶原纤维和混合胶原纤维沉积增加。LDS修饰的Integra支架是一种有前景的新型治疗方法，可加速深度烧伤创面愈合，从而有可能降低与开放性烧伤创面相关的发病率。这些支架还可能减少对自体移植的需求以及对可收获皮肤区域有限的患者的发病率。
