# Open Porous Microenvironment-regulatory Microspheres Loaded with Curcumin@BSA NPs/BMSCs for Diabetic Wound Treatment

**Authors:** Zhe Liu, Qinzhou Zheng, Dong Zhou, Anqi Lin, Lan Xiao, Haifeng Liu, Keqin Ji, Huifen Qiang, Xinxin Sui, Yulin Li, Yan Wu, Jie Gao, Lan Liao, Xiaohuan Yuan

PMC · DOI: 10.7150/thno.120285 · Theranostics · 2026-02-11

## TL;DR

This study develops microspheres that combine curcumin and stem cells to improve wound healing in diabetic patients by regulating the wound environment and promoting tissue regeneration.

## Contribution

A novel open porous microsphere system is introduced for sustained curcumin release and stem cell support in diabetic wound treatment.

## Key findings

- The microspheres enabled 35 days of sustained curcumin release, promoting stem cell proliferation and activity.
- Curcumin and stem cells together improved wound healing by regenerating blood vessels and collagen networks.
- The system activated mitochondrial autophagy, reducing wound inflammation and remodeling the immune microenvironment.

## Abstract

The process of healing wounds in diabetic patients is intricate and is notably obstructed by a disordered wound microenvironment, characterized by chronic inflammation and elevated blood glucose. The combination of stem cell therapy and drug treatment is seen as a promising application in future. However, the limited proliferative capacity of stem cells and inadequate drug availability present significant challenges for achieving optimal therapeutic outcomes.

In this study, open porous poly (lactic‒coglycolic acid) (PLGA) microspheres were designed and synthesized via gas-assisted volatilization microemulsion technology. These microspheres encapsulate curcumin and allow its slow release, thereby enhancing wound repair. The large pores in the microspheres provide ample support for bone marrow stem cells (BMSCs), enabling continuous drug release over a period of 35 days.

The sustained release of curcumin promoted stem cell proliferation and maintained stem cell activity. Additionally, it facilitates remodeling of the wound immune microenvironment. Additionally, the microspheres can activate mitochondrial autophagy in cells, effectively alleviating wound inflammation.

The combined actions of curcumin and stem cells aid in regenerating blood vessels and revitalizing the collagen network where the injury occurred, thus improving wound healing capabilities. Consequently, integrating drugs with stem cells and microspheres holds significant potential for diabetic wound treatment.

## Linked entities

- **Chemicals:** curcumin (PubChem CID 969516)

## Full-text entities

- **Genes:** Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, Map1lc3a (microtubule-associated protein 1 light chain 3 alpha) [NCBI Gene 66734] {aka 1010001H21Rik, 4922501H04Rik, LC3, LC3a}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Mrc1 (mannose receptor, C type 1) [NCBI Gene 17533] {aka CD206, MR}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Acta2 (actin alpha 2, smooth muscle, aorta) [NCBI Gene 11475] {aka 0610041G09Rik, Actvs, SMAalpha, SMalphaA, a-SMA, alphaSMA}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, Adgre1 (adhesion G protein-coupled receptor E1) [NCBI Gene 13733] {aka DD7A5-7, EGF-TM7, Emr1, F4/80, Gpf480, Ly71}, Nup62 (nucleoporin 62) [NCBI Gene 18226] {aka D7Ertd649e, Nupc1, p62}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}
- **Diseases:** hemolysis (MESH:D006461), hypoxia (MESH:D000860), type 1 diabetes mellitus (MESH:D003922), proinflammatory cytokines (MESH:D000080424), hypoxic (MESH:D002534), vascular damage (MESH:D057772), toxicity (MESH:D064420), insulin (MESH:D007333), infection (MESH:D007239), Diabetic (MESH:D003920), diabetic ulcers (MESH:D017719), trauma (MESH:D014947), Inflammation (MESH:D007249), fibrosis (MESH:D005355), Hyperglycemia (MESH:D006943)
- **Chemicals:** formaldehyde (MESH:D005557), CREA (MESH:D003404), ethanol (MESH:D000431), d-glucose (MESH:D005947), DAPI (MESH:C007293), NaOH (MESH:D012972), blood glucose (MESH:D001786), argon (MESH:D001128), EDC (MESH:C024565), Chloroquine (MESH:D002738), PLGA (MESH:D000077182), eosin (MESH:D004801), glutaraldehyde (MESH:D005976), MES (MESH:C004550), PBS (MESH:D007854), acetic acid (MESH:D019342), alcohol (MESH:D000438), PLA (MESH:C033616), LPS (MESH:D008070), urea nitrogen (MESH:C530477), paraformaldehyde (MESH:C003043), MgO (MESH:D008277), Alkali (MESH:D000468), Calcein (MESH:C007740), Streptozotocin (MESH:D013311), CCK-8 (MESH:D012844), polyphenol (MESH:D059808), Water (MESH:D014867), TiO2 (MESH:C009495), CO2 (MESH:D002245), uranium acetate (MESH:C005460), PCL (MESH:C016240), ammonium bicarbonate (MESH:C027043), ester (MESH:D004952), PVA (MESH:C063253), Triton X-100 (MESH:D017830), streptomycin (MESH:D013307), C (MESH:D002244), RAPA (MESH:D020123), Polymer (MESH:D011108), polyacrylamide (MESH:C016679), FITC (MESH:D016650), Poly (vinyl alcohol) (MESH:D011142), bilirubin (MESH:D001663), picrosirius red (MESH:C009798), EDTA (MESH:D004492), UA (MESH:D014527), UREA (MESH:D014508), nitrogen (MESH:D009584), DCM (MESH:D008752), MTT (MESH:C070243), sodium citrate (MESH:D000077559), sugar (MESH:D000073893), PI (MESH:D010716), chitosan (MESH:D048271), NH3 (MESH:D000641), sodium alginate (MESH:D000464), penicillin (MESH:D010406), oxygen (MESH:D010100), hematoxylin (MESH:D006416)
- **Species:** Bacillus sp. SA (species) [taxon 1168094], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), BMSC — Oryctolagus cuniculus (Rabbit), Finite cell line (CVCL_B6BB), NIH-3T3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), HUVEC — Homo sapiens (Human), Finite cell line (CVCL_2959), BMSC@OPM — Homo sapiens (Human), Plasma cell myeloma, Cancer cell line (CVCL_5210)

## Full text

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## Figures

17 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12963991/full.md

## References

116 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963991/full.md

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Source: https://tomesphere.com/paper/PMC12963991