Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Division of Plastic & Reconstructive Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Sci Rep. 2024 Mar 7;14(1):5621. doi: 10.1038/s41598-024-54477-z.
Chronic non-healing wounds significantly strain modern healthcare systems, affecting 1-2% of the population in developed countries with costs ranging between $28.1 and $96.8 billion annually. Additionally, it has been established that chronic wounds resulting from comorbidities, such as peripheral vascular disease and diabetes mellitus, tend to be polymicrobial in nature. Treatment of polymicrobial chronic wounds with oral and IV antibiotics can result in antimicrobial resistance, leading to more difficult-to-treat wounds. Ideally, chronic ulcers would be topically treated with antibiotic combinations tailored to the microbiome of a patient's wound. We have previously shown that a topical collagen-rich hydrogel (cHG) can elute single antibiotics to inhibit bacterial growth in a manner that is nontoxic to mammalian cells. Here, we analyzed the microbiology of cultures taken from human patients diagnosed with diabetes mellitus suffering from chronic wounds present for more than 6 weeks. Additionally, we examined the safety of the elution of multiple antibiotics from collagen-rich hydrogel in mammalian cells in vivo. Finally, we aimed to create tailored combinations of antibiotics impregnated into cHG to successfully target and treat infections and eradicate biofilms cultured from human chronic diabetic wound tissue. We found that the majority of human chronic wounds in our study were polymicrobial in nature. The elution of multiple antibiotics from cHG was well-tolerated in mammalian cells, making it a potential topical treatment of the polymicrobial chronic wound. Finally, combinations of antibiotics tailored to each patient's microbiome eluted from a collagen-rich hydrogel successfully treated bacterial cultures isolated from patient samples via an in vitro assay.
慢性不愈合的伤口对现代医疗体系造成了巨大压力，在发达国家，有 1-2%的人口受到影响，每年的成本在 281 亿至 968 亿美元之间。此外，已经确定，由合并症引起的慢性伤口，如外周血管疾病和糖尿病，往往具有多微生物的性质。用口服和静脉内抗生素治疗多微生物慢性伤口会导致抗生素耐药性，从而导致更难治疗的伤口。理想情况下，慢性溃疡应该用针对患者伤口微生物组的抗生素组合进行局部治疗。我们之前已经表明，富含胶原蛋白的水凝胶（cHG）可以洗脱单一抗生素，以非毒性方式抑制哺乳动物细胞的细菌生长。在这里，我们分析了从患有糖尿病的慢性伤口超过 6 周的人类患者中获取的培养物的微生物学。此外，我们还研究了从富含胶原蛋白的水凝胶中洗脱多种抗生素在哺乳动物细胞中的体内安全性。最后，我们旨在创建浸渍有抗生素的 cHG 的定制组合，以成功靶向和治疗感染并根除从人类慢性糖尿病性伤口组织培养的生物膜。我们发现，我们研究中的大多数人类慢性伤口都是多微生物的。从 cHG 洗脱多种抗生素在哺乳动物细胞中耐受良好，使其成为多微生物慢性伤口的潜在局部治疗方法。最后，从富含胶原蛋白的水凝胶中洗脱的针对每个患者微生物组的抗生素组合通过体外测定成功治疗了从患者样本中分离的细菌培养物。
