https://doi.org/10.1016/j.bioactmat.2022.04.020

Smart bioadhesives for wound healing and closure

Hemostatic biomaterials show great promise in wound control for the treatment of uncontrolled bleeding associated with damaged tissues, traumatic wounds, and surgical incisions. A surge of interest has been directed at boosting hemostatic properties of bioactive materials via mechanisms triggering the coagulation cascade. A wide variety of biocompatible and biodegradable materials has been applied to the design of hemostatic platforms for rapid blood coagulation. Recent trends in the design of hemostatic agents emphasize chemical conjugation of charged moieties to biomacromolecules, physical incorporation of blood-coagulating agents in biomaterials systems, and superabsorbing materials in either dry (foams) or wet (hydrogel) states. In addition, tough bioadhesives are emerging for efficient and physical sealing of incisions. In this Review, we highlight the biomacromolecular design approaches adopted to develop hemostatic bioactive materials. We discuss the mechanistic pathways of hemostasis along with the current standard experimental procedures for characterization of the hemostasis efficacy. Finally, we discuss the potential for clinical translation of hemostatic technologies, future trends, and research opportunities for the development of next-generation surgical materials with hemostatic properties for wound management.

Engineered Hemostatic Biomaterials for Sealing Wounds.

Mucoadhesion is an extremely important field of adhesion science and the comprehensive understanding and modulation of mucoadhesion can lead to lifesaving materials and technologies. For instance, deadly cases of COVID‐19 (SARS‐CoV‐2) cytokine storm are associated with viral adhesion and overproduction of mucus, which obstructs the airways. Mucin is the key polymeric compound that is known as a family of high molecular weight, heavily glycosylated proteins in epithelial tissues. Mucoadhesion can occur in many different ways such as receptor specific and charge interactions, covalent or noncovalent bonds. New mucin‐mimic polymers that replicate its beneficial traits can prevent biofilm formation and biofouling not only in biotechnology but also in membrane technologies. This review addresses the latest understandings related to mucin's role in wet adhesion considering different physiological conditions and shows how this translates into interfacial polymer adhesion. Advances in mucoadhesion measurement techniques including the rheological aspects of polymer–mucin adhesive interactions are presented. Specific mucoadhesive systems are discussed such as hydrogel mucoadhesion, catechol/dopamine functionalization, and polymeric nanoparticles. This overview may expand the current understanding of mucoadhesion between soft materials but also contributes to elastocapillary phenomena in soft materials design and applications such as new membranes, drugs, pharmaceutical devices, and lubricated surfaces.

Recent Advances in Mucoadhesive Interface Materials, Mucoadhesion Characterization, and Technologies

https://doi.org/10.1016/j.bioactmat.2022.01.034

3D printed biomimetic epithelium/stroma bilayer hydrogel implant for corneal regeneration

BACKGROUND
Ocular burns cause depletion of limbal stem cells, which leads to corneal opacification and visual loss. Autologous cultured epithelial cells can restore damaged corneas, but this technology is still developing. We sought to establish a culture system that allows preservation of limbal stem cells and preparation of manageable epithelial sheets and to investigate whether such cultures can permanently restore total limbal stem cell deficiency.


METHODS
We selected a homogeneous group of patients whose limbal cell deficiency was evaluated by scoring the gravity of the clinical picture and the keratin expression pattern. Stem cells, obtained from the limbus of the contralateral eye, were cultivated onto a fibrin substrate and their preservation was evaluated by clonal analysis. Fibrin cultures were grafted onto damaged corneas.


RESULTS
Fibrin-cultured limbal stem cells were successful in 14 of 18 patients. Re-epithelialization occurred within the first week. Inflammation and vascularization regressed within the first 3-4 weeks. By the first month, the corneal surface was covered by a transparent, normal-looking epithelium. At 12-27 months follow-up, corneal surfaces were clinically and cytologically stable. Three patients had a penetrating keratoplasty approximately 1 year after restoration of their corneal surface. Their visual acuity improved from light perception or counting fingers to 0.8-1.0.


CONCLUSIONS
Preservation of limbal stem cells in culture gives new perspectives on the treatment of ocular disorders characterized by complete limbal stem cell deficiency. The multicenter nature of this study and the handiness and ease of long-distance transportation of the fibrin-cultured epithelial sheets suggest that this technology can now be widely applied.

Autologous fibrin-cultured limbal stem cells permanently restore the corneal surface of patients with total limbal stem cell deficiency. [5YIF: 3.60; Citations: 297]

Natural polymer-derived photocurable bioadhesive hydrogels for sutureless keratoplasty.

Simple Summary About 10–20% of breast cancer patients have a heterogeneous estrogen receptor expression. The diagnosis and treatment strategy remains controversial in these patients, especially regarding the metastatic pattern. The aim of our study was to investigate the occurrence and properties of estrogen receptor heterogeneity and to evaluate the following treatment efficacy among a certain group of metastatic breast cancer patients. We found the novel 18F-FES PET/CT method could identify patients with estrogen receptor heterogeneity, and chemotherapy showed a better efficacy compared with endocrine therapy in these patients. Our findings could give valuable suggestions to physicians and researchers in clinical practice. Abstract Background: The heterogeneity of estrogen receptor (ER) expression has long been a challenge for the diagnosis and treatment strategy of metastatic breast cancer (MBC). A novel convenient method of ER detection using 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) offers a chance to screen and analyze MBC patients with ER uncertainty. Methods: MBC patients who received 18F-FES PET/CT were screened and patients with both FES positive (FES+) and negative (FES-) lesions were enrolled in this study. Progression-free survival (PFS) was estimated using the Kaplan–Meier method and was compared using the log-rank test. Results: A total of 635 patients were screened and 75 of 635 (11.8%) patients showed ER uncertainty; 51 patients received further treatment and were enrolled in this study. Among them, 20 (39.2%) patients received chemotherapy (CT), 21 (41.2%) patients received endocrine-based therapy (ET), and 10 (19.6%) patients received combined therapy (CT + ET). CT showed a better progression-free survival (PFS) compared with ET (mPFS 7.1 vs. 4.6 months, HR 0.44, 95% CI 0.20–0.93, p = 0.03). CT + ET did not improve PFS compared with either CT or ET alone (mPFS 4.4 months, p > 0.2). All three treatment options were well tolerated. Conclusions: 18F-FES PET/CT could identify patients with ER heterogeneity. Patients with bone metastasis are more likely to have ER heterogeneity. Patients with ER heterogeneity showed better sensitivity to CT rather than ET. Combined therapy of CT + ET did not improve the treatment outcome.

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Chemotherapy Shows a Better Efficacy Than Endocrine Therapy in Metastatic Breast Cancer Patients with a Heterogeneous Estrogen Receptor Expression Assessed by 18F-FES PET

Limited studies have explored the association between visceral adipose tissue (VAT) mass and fat‐to‐muscle mass ratio (FMR) and mortality. We aimed to evaluate the sex‐specific association of VAT and FMR with all‐cause and cause‐specific mortality by age.

Age‐specific and sex‐specific associations of visceral adipose tissue mass and fat‐to‐muscle mass ratio with risk of mortality

Purpose: To evaluate corneal elevation changes in patients with allergic conjunctivitis (AC) and to analyze their correlations with ocular allergy signs and corneal biomechanical alterations. Methods: Thirty patients (30 eyes) with AC and twenty normal subjects (20 eyes) were included in this prospective study. All participants underwent a complete ocular examination, including corneal tomography by Pentacam and corneal biomechanics evaluation by Corvis ST. AC patients were evaluated for their eye rubbing frequency and ocular allergic signs. Results: The elevation at the thinnest location (TE) and the central location (CE), the elevation difference at the thinnest location (TED) and the central location (CED), and the mean value of elevation difference in the central 4 mm zoom (MED) of both the anterior and posterior corneal surface were significantly higher in the AC group than in the normal group (p<0.05 for all). In AC patients, only anterior corneal elevation parameters were positively correlated with eye rubbing frequency and ocular allergy sign severity (p<0.05 for all), while the tomography and biomechanical index (TBI) was positively correlated with the elevation parameters of both the anterior and posterior corneal surfaces (p<0.05 for all). Conclusions: AC patients carry an increased risk of corneal ectasia. Posterior corneal elevation parameters are sensitive and reliable predictors of keratoconus (KC) risk in AC patients.

Changes in Anterior and Posterior Corneal Elevation in Patients With Allergic Conjunctivitis

Conventional administration of eye drops often requires high dosages and/or repetitive treatments to achieve therapeutic efficacy. This is inefficient and may result in side effects or even toxicity. Although many delivery systems of ophthalmic drugs have been reported, most of them work in a fixed format in which both the type and dose of the loaded drugs cannot be changed upon demand. To overcome this limitation, a hybrid double network hydrogel system composed of methacryloyl gelatin, pluronic F127 diacrylate, and β-cyclodextrin-modified oxidized dextran was developed. The hydrogels presented good mechanical strength and biocompatibility. In vitro assessments demonstrated that the hydrogels loaded with commonly used ophthalmic drugs could sustain the drug release for more than 21 days. This hydrogel system exhibited features of mechanoresponsive drug loading, and the capacity of drug loading could be significantly enhanced by macroscopically mechanical compression. Further in vivo evaluation of the drug delivery capacity showed that a dexamethasone-loaded hydrogel as a fornix insert effectively suppressed upregulation of proangiogenic factors and suture-induced corneal neovascularization in rats. This novel hydrogel system represents a promising drug delivery platform, which could potentially improve the treatments of ocular surface and other diseases.

Xinyue Du

Papers

Natural polymer-derived photocurable bioadhesive hydrogels for sutureless keratoplasty.

Chemotherapy Shows a Better Efficacy Than Endocrine Therapy in Metastatic Breast Cancer Patients with a Heterogeneous Estrogen Receptor Expression Assessed by 18F-FES PET

Age‐specific and sex‐specific associations of visceral adipose tissue mass and fat‐to‐muscle mass ratio with risk of mortality

Changes in Anterior and Posterior Corneal Elevation in Patients With Allergic Conjunctivitis

Mechanoresponsive Drug Loading System with Tunable Host-Guest Interactions for Ocular Disease Treatment.