LATEST PUBLICATIONS
Paper | 01
A near-infrared fluorescent pH indicator film for wound milieu pH monitoring.
Li S, Vu H, Senkowsky J, Hu W, Tang L. Experimental Dermatology. 2019.
https://doi.org/10.1111/exd.14046
Studies have shown that wound pH is a potentially influential factor in the healing process. Due to the flaws of traditional pH measurement approaches, wound pH measurement has not become part of the current standard of care. A near-infrared pH-sensitive ratiometric film was created and characterized for measuring wound pH. This film was fabricated by physically absorbing poly (N-isopropyl Acrylamide) nanoparticles conjugated with pH-sensitive (CypHer5E) and pH insensitive (Cy7) fluorescent dyes into 2-hydroxyethyl methacrylate hydrogel film. The pH pattern on wounds can be indirectly measured by pressing freshly discarded wound dressing on top of the pH-sensitive film and imaging it. In vitro tests show that the film can accurately and rapidly detect a wide range of pH (from pH 4 to 8) in wound milieu. Further, patient studies showed that, by measuring pH on the wound contact side of discarded wound gauze, the pH and its non-homogeneous distribution on wounds can be indirectly determined. By comparing patients with different wound conditions, we find that near-infrared pH sensing film can be used to measure wound exudate pH with high accuracy and efficiency. In addition, wound pH determination can provide an accurate assessment of wound healing activity in real-time.
Paper | 02
Imaging in Chronic Wound Diagnostics.
Li S, Ali H M, Senkowsky J, Nair A, Tang L. Advances in Wound Care 2020; 9 (5):245-263. http://doi.org/10.1089/wound.2019.0967
Significance: Chronic wounds affect millions of patients worldwide, placing a huge burden on health care resources. Although significant progress has been made in the development of wound treatments, very few advances have been made in wound diagnosis.
Recent Advances: Standard imaging methods like computed tomography, single-photon emission computed tomography, magnetic resonance imaging, terahertz imaging, and ultrasound imaging have been widely employed in wound diagnostics. A number of noninvasive optical imaging modalities like optical coherence tomography, near-infrared spectroscopy, laser Doppler imaging, spatial frequency domain imaging, digital camera imaging, and thermal and fluorescence imaging have emerged over the years.
Critical Issues: While standard diagnostic wound imaging modalities provide valuable information, they cannot account for dynamic changes in the wound environment. In addition, they lack the capability to predict the healing outcome. Thus, there remains a pressing need for more efficient methods that can not only indicate the current state of the wound but also help determine whether the wound is on track to heal normally.
Future Directions: Many imaging probes have been fabricated and shown to provide real-time assessment of tissue microenvironment and inflammatory responses in vivo. These probes have been demonstrated to noninvasively detect various changes in the wound environment, which include tissue pH, reactive oxygen species, fibrin deposition, matrix metalloproteinase production, and macrophage accumulation. This review summarizes the creation of these probes and their potential implications in wound monitoring.
Paper | 03
Hyaluronic Acid-Based Optical Probe for the Diagnosis of Human Osteoarthritic Cartilage.
Li S, Cong W, Hakamivala A, Huang Y, Borrelli J Jr, Tang L. Nanotheranostics 2018; 2(4):347-359.
http://www.ntno.org/v02p0347.htm
Osteoarthritis is typically caused by cartilage injury, followed by localized inflammatory responses and tissue deterioration. Early treatment of osteoarthritis is often impossible due to the lack of diagnostic options. Recent studies have supported that different imaging probes can be used for arthritis detection in mice. However, none of these diagnostic tools have been tested on human articular cartilage. To fill this gap, an optical imaging probe was developed to target activated macrophages and the accumulation of imaging probes on tissue was used to assess the severity of human osteoarthritis.
Methods: The probe was fabricated using hyaluronic acid (HA) particles conjugated with near-infrared dye and folic acid (FA). The ability of the FA-HA probes to detect activated macrophages and quantify cartilage injury was evaluated using a cell culture model in vitro and human osteoarthritic cartilage explants ex vivo.
Results: Our cell study results supported that the FA-HA probes are cell compatible (up to 0.5mg/mL) and can detect activated macrophages in 30 minutes. Using human articular cartilage, we verified the existence of activated macrophages on osteoarthritic cartilage with highly up-regulated expression of folate receptors (~13 folds by comparison with healthy control). In addition, we found that FA-HA probes had higher binding amounts (~3 folds) to osteoarthritic tissue than healthy ones. Histological analyses confirmed that there was a strong linear relationship (R=0.933) between the fluorescent intensity of tissue-associated probe and the extent of folate receptors on osteoarthritic cartilage. Finally, the co-localization of the imaging probe, folate receptors and cartilage degeneration on the tissue sections indicated the extraordinary accuracy and efficiency of this osteoarthritis diagnostic probe.
Conclusions: Our results support the probe as an effective diagnostic tool to detect the area and severity of osteoarthritic human articular cartilage.
Paper | 04
Diagnostics for Wound Infections.
Li S, Renick P, Senkowsky J, Nair A, Tang L. Advances in Wound Care. 2020.
https://doi.org/10.1089/wound.2019.1103
Significance: Infections can significantly delay the healing process in chronic wounds, placing an enormous economic burden on health care resources. Identification of infection biomarkers and imaging modalities to observe and quantify them has seen progress over the years.
Recent Advances: Traditionally, clinicians determine the presence of infection through visual observation of wounds and confirm their diagnosis through wound culture. Many laboratory markers, including C-reactive protein, procalcitonin, presepsin, and bacterial protease activity, have been quantified to assist diagnosis of infection. Moreover, imaging modalities like plain radiography, computed tomography, magnetic resonance imaging, ultrasound imaging, spatial frequency domain imaging, thermography, autofluorescence imaging, and biosensors have emerged for real-time wound infection diagnosis and showed their unique advantages in deeper wound infection diagnosis.
Critical Issues: While traditional diagnostic approaches provide valuable information, they are time-consuming and depend on clinicians' experiences. There is a need for noninvasive wound infection diagnostics that are highly specific, rapid, and accurate, and do not require extensive training.
Future Directions: While innovative diagnostics utilizing various imaging instrumentation are being developed, new biomarkers have been investigated as potential indicators for wound infection. Products may be developed to either qualitatively or quantitatively measure these biomarkers. This review summarizes and compares all available diagnostics for wound infection, including those currently used in clinics and still under development. This review could serve as a valuable resource for clinicians treating wound infections as well as patients and wound care providers who would like to be informed of the recent developments.
Paper | 05
Injectable Click Chemistry-based Bioadhesives for Accelerated Wound Closure.
Li S, Zhou J, Huang Y, Roy J, Zhou N, Yum K, Sun X, Tang L. Acta Biomaterialia 2020; 110:95-104.
https://doi.org/10.1016/j.actbio.2020.04.004
Tissue adhesives play a vital role in surgical processes as a substitute for sutures in wound closure. However, several existing tissue adhesives suffer from cell toxicity, weak tissue-adhesive strength, and high cost. In this study, by taking advantage of the fast and specific inverse-demand Diels-Alder cycloaddition reaction, a series of bioadhesives were produced by employing copper-free click chemistry pair trans-cyclooctene (TCO) /tetrazine (Tz) in chitosan. The gelation time of the bioadhesives can be optimized to be less than 2 minutes, which meets the need for surgical wound closure in practice. By adding 4-arm polyethylene glycol propionaldehyde (PEG-PALD) as a co-crosslinker, the adhesive strength of the bioadhesives was optimized to be 2.3 times higher than that of the conventional fibrin glue. Moreover, by adjusting the amount of the co-crosslinker, the swelling ratio and pore size of the chitosan bioadhesives can be tuned to fit the need of drug encapsulation and cell seeding. The chitosan bioadhesives possess no significant in vitro cytotoxicity. Using a mice skin incision wound model, we found that the chitosan bioadhesives were able to close the wound faster and promote wound healing process than the fibrin glue. In conclusion, our results support that the innovative click-chemistry based bioadhesives have been developed with improved physical and biological properties for surgical wound closures.