I work on the development of new wound dressings to help chronic wounds heal.
Chronic wounds occur when a wound does not enter the healing phase, but rather stays in a prolonged inflammatory response. These wounds do not close and cause severe pain to the patient. In my work I develop new dressing materials to address the underlying imbalance between inflammatory and regenerative signaling mediators. Through novel biomaterial-based therapeutic approaches the inflammation can be decreased allowing the body to heal.
Abstract: Dressing materials involve conventional gauzes and modern materials such as hydrogels and foam-based biomaterials. Although the choice of dressing material depends on the type of wound, a dressing material is expected to be non-cytotoxic. Additionally, moist dressing is considered appropriate to accelerate epithelialisation, while dry dressing may cause tissue damage during removal. An ideal dressing material is expected to provide a moist environment and degrade and release the drug for faster wound healing. Thus, we have designed a hydrogel-based biodegradable dressing material to provide the moist environment with no cytotoxic effect in vitro. The design of the hydrogel involved alginate-collagen reinforced with whisker cellulose derived from cotton. The hydrogel was prepared via amide linkage in the presence of 1-ethyl-(dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysulfosuccinimide (NHS), followed by divalent cationic cross-linking of alginate and hydrogen bonding with cellulose. The high water retention capability of the hydrogel enables a moist environment to be maintained in the wounded area. The constituents of the hydrogel provided a microenvironment that was suitable for cell proliferation in the vicinity of the hydrogel but inhibited cell attachment on it. The MTT assay results indicated a higher fibroblast proliferation and viability in the presence of the hydrogel.
Pub.: 26 Apr '17, Pinned: 25 Aug '17
Abstract: Macrophages are versatile and plastic effector cells of the immune system, and contribute to diverse immune functions including pathogen or apoptotic cell removal, inflammatory activation and resolution, and tissue healing. Macrophages function as signaling regulators and amplifiers and influencing their activity is a powerful approach for controlling inflammation or inducing a wound-healing response in regenerative medicine. This review discusses biomaterials-based approaches for altering macrophage activity, approaches for targeting drugs to macrophages, and approaches for delivering macrophages themselves as a therapeutic intervention.
Pub.: 30 Apr '17, Pinned: 25 Aug '17
Abstract: While early excision and grafting has revolutionized burn wound care, autologous split-thickness skin grafts are sometimes unavailable. Tissue-engineered skin substitutes have generated great interest but have proven inadequate. Therefore, the development of novel biomaterials to replace/augment skin grafting could improve burn patient outcomes. Herein, we establish the effects of debridement on deep-partial thickness burns and subsequently examine the effects of 3 different hydrogels on healing. Burns were created on the dorsum of pigs and 4 days after, the eschar was either left intact or debrided for treatment with collagen, PEGylated fibrinogen (PEG-fibrin) or PEGylated autologous platelet-free plasma hydrogels. Wounds were photographed, scored, and biopsied for histology on postburn days 7, 10, 14, and 28. Compared with nondebrided wounds, debridement improved wound color and suppleness but accelerated contraction. Debridement also significantly reduced the number of neutrophils in the wound bed at days 10 and 14 postburn. Treatment with any hydrogel transiently mitigated contraction, with the PEG-fibrin group displaying less contraction on day 28. All hydrogels were visible histologically for up to 10 days, with significant cellular and blood vessel infiltration observed in PEG-fibrin hydrogels. Collagen and PEG-fibrin hydrogels reduced neutrophils and macrophages in surrounding granulation tissue on day 7 and the PEG-fibrin hydrogels containing less immune cells. These data suggest that a single hydrogel application at the time of debridement has immunomodulatory properties that aid in wound healing. Ultimately, these hydrogels may be combined with other biomaterials, cells, or biologics for replacing/augmenting skin substitutes.
Pub.: 31 May '17, Pinned: 25 Aug '17
Abstract: Scarring of the vocal fold lamina propria can lead to debilitating voice disorders that can significantly impair quality of life. The reduced pliability of the scar tissue-which diminishes proper vocal fold vibratory efficiency-results in part from abnormal extracellular matrix (ECM) deposition by vocal fold fibroblasts (VFF) that have taken on a fibrotic phenotype. To address this issue, bioactive materials containing cytokines and/or growth factors may provide a platform to transition fibrotic VFF within the scarred tissue toward an anti-fibrotic phenotype, thereby improving the quality of ECM within the scar tissue. However, for such an approach to be most effective, the acute host response resulting from biomaterial insertion/injection likely also needs to be considered. The goal of the present work was to evaluate the anti-fibrotic and anti-inflammatory capacity of an injectable hydrogel containing tethered basic fibroblast growth factor (bFGF) in the dual context of scar and biomaterial-induced acute inflammation. An in vitro co-culture system was utilized containing both activated, fibrotic VFF and activated, pro-inflammatory macrophages (MΦ) within a 3D poly(ethylene glycol) diacrylate (PEGDA) hydrogel containing tethered bFGF. Following 72 h of culture, alterations in VFF and macrophage phenotype were evaluated relative to mono-culture and co-culture controls. In our co-culture system, bFGF reduced the production of fibrotic markers collagen type I, α smooth muscle actin, and biglycan by activated VFF and promoted wound-healing/anti-inflammatory marker expression in activated MΦ. Cumulatively, these data indicate that bFGF-containing hydrogels warrant further investigation for the treatment of vocal fold lamina propria scar. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017.
Pub.: 06 Jun '17, Pinned: 25 Aug '17
Abstract: The present study reports the development of a novel film-forming bovine collagenous cream (BCC) based on bovine collagen (BC). In this study, collagen was isolated from bovine forestomach tissue, a novel source, and a cream formulation was prepared using some other bioactive ingredients. The electrophoretic pattern of the BC was found to be similar to type I collagen. The purity of BC was examined by amino acid analysis, which confirmed the presence of atelocollagen. The physicochemical properties of BCC such as rheology, spreadability, and temperature stability were characterized. The antimicrobial activity was examined against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, and BCC displayed excellent inhibitory effect. In vitro biocompatibility studies using NIH 3T3 fibroblast cells showed enhanced cell viability. FACS analysis revealed the non-toxic nature of BCC toward cells. The cell morphology and proliferation on the BCC matrix was studied using SEM and fluorescence microscopy. The in vivo wound healing efficacy of the BCC as a topical wound dressing was demonstrated on full thickness excision wounds in rat models. The healing profile showed that the BCC significantly enhanced re-epithelialization, collagen deposition, and contraction in the wound healing process. The findings of this study provide a new opportunity for the utilization of the untapped byproducts of the meat industry for valorization. We expect that this kind of topical healing cream could be a potential candidate in wound management and future clinical needs.
Pub.: 06 Jul '17, Pinned: 25 Aug '17
Abstract: Fibroblasts are key participants in wound healing and inflammation, and are capable of driving the progression of tissue repair to fully functional tissue or pathologic scar, or fibrosis, depending on the specific mechanical and biochemical cues with which they are presented. Thus, understanding and modulating the fibroblastic response to implanted materials is paramount to achieving desirable outcomes, such as long-term implant function or tissue regeneration. However, fibroblasts are remarkably heterogeneous and can differ vastly in their contributions to regeneration and fibrosis. This heterogeneity exists between tissues and within tissues, down to the level of individual cells. This review will discuss the role of fibroblasts, the pitfalls of describing them as a collective, the specifics of their function, and potential future directions to better understand and organize their highly variable biology.
Pub.: 13 Jun '17, Pinned: 25 Aug '17
Abstract: A surgical suture is a medical device to close the wound site of skin and organs but excessive inflammation surrounding the suture can disrupt the wound healing process. Although post-operative prescription of anti-inflammatory drugs is used to manage the inflammation, the need for local drug delivery systems has been rising because of low bioavailability and fast clearance of drugs. In this work, we proposed a new strategy for a local anti-inflammatory device by incorporating macrophage-targeted anti-inflammatory nanoparticles into the suture. For macrophage-targeted anti-inflammatory nanoparticles, poly(lactic-co-glycolic) nanoparticles were loaded with anti-inflammatory drug diclofenac and decorated with polyethylene glycol and macrophage-targeting ligand mannose. These anti-inflammatory nanoparticles released diclofenac sustainably, and targeted activated macrophages efficiently. After nanoparticle optimization, a suture was coated with multiple layers of macrophage-targeted anti-inflammatory nanoparticles using a dip coating process. The suture releasing macrophage-targeted anti-inflammatory nanoparticles showed an enhanced anti-inflammatory effect in both macrophage culture and excisional wound healing animal models compared to a free drug molecule-coated suture. These results suggest that anti-inflammatory nanoparticle-coated sutures have great potential as an effective local delivery system to reduce inflammation and pain at the wound site.
Pub.: 18 Jul '17, Pinned: 25 Aug '17
Abstract: Diabetic wound is a common complication of diabetes. Biomaterials offer great promise in inducing tissue regeneration for chronic wound healing. Herein, we reported a conducive Poly (caprolactone) (PCL)/gelatin nanofibrous composite scaffold containing silicate-based bioceramic particles (Nagelschmidtite, NAGEL, Ca7P2Si2O16) for diabetic wound healing. NAGEL bioceramic particles were well distributed in the inner of PCL/gelatin nanofibers via co-electrospinning process and the Si ions maintained a sustained release from the composite scaffolds during the degradation process. The nanofibrous scaffolds significantly promoted the adhesion, proliferation and migration of human umbilical vein endothelial cells (HUVECs) and human keratinocytes (HaCaTs) in vitro. The in vivo study demonstrated that the scaffolds distinctly induced the angiogenesis, collagen deposition and re-epithelialization in the wound sites of diabetic mice model, as well as inhibited inflammation reaction. The mechanism for nanofibrous composite scaffolds accelerating diabetic wound healing is related to the activation of epithelial-to-mesenchymal transition (EMT) and endothelial mesenchymal transformation (EndMT) pathway in vivo and in vitro. Our results suggest that the released Si ions and nanofibrous structure of scaffolds have a synergetic effect on the improved efficiency of diabetic wound healing, paving the way to design functional biomaterials for tissue engineering and wound healing applications. Statement of significance In order to stimulate tissue regeneration for chronic wound healing, a new kind of conducive nanofibrous composite scaffold containing silicate-based bioceramic particles (Nagelschmidtite, NAGEL, Ca7P2Si2O16) were prepared via co-electrospinning process. Biological assessments revealed that the NAGEL bioceramic particles could active epithelial-to-mesenchymal transition (EMT) and endothelial mesenchymal transformation (EndMT) pathway in vitro and in vivo. The new composite scaffold had potential as functional biomaterials for tissue engineering and wound healing applications. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors on nanofibrous composite scaffold provides new options for bioactive biomaterials.
Pub.: 18 Jul '17, Pinned: 25 Aug '17
Abstract: Biocompatibility is a major concern for developing biomaterials used in medical devices, tissue engineering and drug delivery. Poly(lactic-co-glycolic acid) (PLGA) is one of the most widely used biodegradable materials, yet still triggers a significant foreign body response that impairs healing. Immune cells including macrophages respond to the implanted biomaterial and mediate the host response, which can eventually lead to device failure. Previously in our laboratory, we found that CD200, an immunomodulatory protein, suppressed macrophage inflammatory activation in vitro and reduced local immune cell infiltration around a biomaterial implant. While in our initial study we used polystyrene as a model material, here we investigate the effect of CD200 on PLGA, a commonly used biomaterial with many potential clinical applications. We fabricated PLGA with varied geometries, modified their surfaces with CD200, and examined macrophage cytokine secretion and phagocytosis. We found that CD200 suppressed secretion of the pro-inflammatory cytokine TNF-α and enhanced secretion of the anti-inflammatory cytokine IL-10, suggesting a role for CD200 in promoting wound healing and tissue remodeling. In addition, we found that CD200 increased phagocytosis in both murine macrophages and human monocytes. Together, these data suggest that modification with CD200 leads to a response that simultaneously prevents inflammation and enhances phagocytosis. This immunomodulatory feature may be used as a strategy to mitigate inflammation or deliver drugs or anti-inflammatory agents targeting macrophages.
Pub.: 25 Jul '17, Pinned: 25 Aug '17
Abstract: Avian eggshell membrane (ESM) is a natural biomaterial that has been used as an alternative natural bandage on burned and cut skin injuries for >400 years in Asian countries, and is available in large quantities from egg industries. Our aim was to characterize ESM that was separated and processed from egg waste, and to study whether this material possesses anti-inflammatory properties, making it suitable as an ingredient in industrial production of low cost wound healing products. Our results show that the processed ESM particles retain a fibrous structure similar to that observed for the native membrane, and contain collagen, and carbohydrate components such as hyaluronic acid and sulfated glycosaminoglycans, as well as N-glycans, mostly with uncharged structures. Furthermore, both processed ESM powder and the ESM-derived carbohydrate fraction had immunomodulation properties in monocytes and macrophage-like cells. Under inflammatory conditions induced by lipopolysaccharide, the ESM powder and the isolated carbohydrate fraction reduced the activity of the transcription factor nuclear factor-κB. The expression of the immune regulating receptors toll-like receptor 4 and ICAM-1, as well as the cell surface glycoprotein CD44, all important during inflammation response, were down-regulated by these fractions. Interestingly, our experiments show that the two fractions regulated cytokine secretion differently: ESM depressed inflammation by increased secretion of the anti-inflammatory cytokine IL-10 while the carbohydrate fraction reduced secretions of the pro inflammatory cytokines IL-1β and IL-6. Also, the phosphorylation of p65 and p50 subunits of nuclear factor-κB, as well as nuclear localization, differed between processed ESM powder and carbohydrate fraction, suggesting different down-stream regulation during inflammation. In conclusion, processed ESM powder and its soluble carbohydrate components possess anti-inflammatory properties, demonstrating the potential of ESM as a novel biological wound dressing for treatment of chronic inflammatory wounds.
Pub.: 26 Jul '17, Pinned: 25 Aug '17