Living Microneedle Patch with Adipose‐Derived Stem Cells Embedding for Diabetic Ulcer Healing

Abstract

Stem cells have demonstrated values in diabetic ulcer (DU) treatments. Challenges in this area are focused on enhancing the localized curative effects of stem cells and improving diabetic wound healing efficiently. Herein, a novel living microneedle (MN) patch is presented as a localized delivery system of bioactive platelet derived growth factor D (PDGF-D) and human adipose-derived stem cells (ADSCs) for DU wound treatment. Compared with traditional complicated stem cell carriers, the MN patch can keep stem cell viability for ADSCs encapsulation and delivery, and possesses good mechanical strengths to penetrate the local skin wounds noninvasively. It is demonstrated that the delivery ADSCs are with the abilities of angiogenesis promotion during the DU wound healing; while the additive PDGF-D can contribute significantly to the proliferation of ADSCs, strengthening the cell function of ADSCs and further facilitating the healing processes. Thus, living MN patches accelerate vascularization, tissue regeneration, and collagen deposition in a wounded diabetic mouse model, suggesting their potential application to DU wound healing and other therapeutic applications.

Microneedles for in situ tissue regeneration

“…As shown in Fig. 3 A and B, Prof. Zhao's group fabricated methacrylated HA (HAMA) hydrogel MNs encapsulated with bioactive platelet-derived growth factor D (PDGF-D) and human adipose stem cells (ADSCs) [ 72 ]. The HAMA MNs could maintain the activity of ADSCs over 90% for 24 ​h, enhance the biological function of ADSCs to secret growth factor and promote diabetic wound healing by accelerating vascularization, tissue regeneration and collagen deposition.…”

“…3 A) Schematic illustrations of the MNs loaded with ADSCs and PDGF-D. B) Application of MNs for diabetic wound treatment (Reproduced with permission of Ref. [ 72 ]). C) Schematic diagram of transfer-molded MN for localized and minimally invasive ocular drug delivery (Reproduced with permission of Ref.…”

“… Base: gelatin Needles: HAMA Arrays: - Height: 800 ​μm Shape: conical Strength: Failure force about 2 ​N Platelet derived growth factor D, human adipose-derived stem cells Ensuring sufficient nutrient supply to sustain viability of cells >90% for 24 ​h. [ 72 ] Needles: GelMA Base: polyvinyl acetate Arrays:- Height:- Shape: conical Strength: >0.5 ​N/needle Oxygen The base would soon disappear by dissolving within 10 ​min; Using the photothermal effect of the black phosphorus and the reversible oxygen-binding property of hemoglobin, the needle tip released oxygen under NIR irradiation. [ 80 ] Needle: outer PLGA shell and internal GelMA Base: doublesided tape Arrays:- Height: 700 ​μm Shape: conical Strength: Failure force of 1–1.5 ​N Mesenchymal stem cells >90% of MNs fall off over 1 ​min; Cell viability remained above 90% up to 24 ​h in MNs; Delivery of cell-secreted VEGF.…”

Blue-ringed octopus-inspired microneedle patch for robust tissue surface adhesion and active injection drug delivery

“…Intratissue topical medication has the merits of quick action, high drug bioavailability, and minimal invasiveness, supplying rapid and effective treatment in inhibiting tumor growth, reducing organ diseases, or accelerating trauma healing (1)(2)(3). However, many issues remain to be addressed for the thorough development of this drug delivery method.…”

Microneedles: a novel strategy for wound management

“…Microneedle (MN) patches are a novel form of transdermal drug delivery in which therapeutic drugs are efficiently delivered transdermally by penetrating these protective layers in a minimally invasive way with a needle body of hundreds of micrometers in height. 43–47 To date, various matrix materials have been employed to fabricate MNs, 48–52 including polylactic acid (PLA), silicon, stainless steel, and light-curing resin for generating MNs. Polyvinyl alcohol (PVA), hyaluronic acid (HA), silk protein, and gelatin have been utilized to form soluble MNs, while gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), and sodium alginate have been employed to form hydrogel MNs.…”