Precise delivery of therapeutics to the target structures is essential for treatment efficiency and safety. Drug administration via conventional routes requires overcoming multiple transport barriers to achieve and maintain the local drug concentration and commonly results in unwanted off-target effects. Patients’ compliance with the treatment schedule remains another challenge. Implantable drug delivery systems (IDDSs) provide a way to solve these problems. IDDSs are bioengineering devices surgically placed inside the patient’s tissues to avoid first-pass metabolism and reduce the systemic toxicity of the drug by eluting the therapeutic payload in the vicinity of the target tissues. IDDSs present an impressive example of successful translation of the research and engineering findings to the patient’s bedside. It is envisaged that the IDDS technologies will grow exponentially in the coming years. However, to pave the way for this progress, it is essential to learn lessons from the past and present of IDDSs clinical applications. The efficiency and safety of the drug-eluting implants depend on the interactions between the device and the hosting tissues. In this review, we address this need and analyze the clinical landscape of the FDA-approved IDDSs applications in the context of the foreign body reaction, a key aspect of implant–tissue integration.

Peri-implant fibrosis (PIF) increases the postsurgical risks after implantation and limits the efficacy of the implantable drug delivery systems (IDDS). Pirfenidone (PF) is an oral anti-fibrotic drug with a short (1100 μm in control groups) approaching the intact derma thickness value (302 ± 15 μm). In PLA@PF group, the implant biodegradation developed faster, while arginase-1 expression was suppressed in comparison with other groups. This study proves the feasibility of the local control of fibrotic response on implants via modulation of foreign body reaction with slowly biodegradable PF-loaded IDDS.

The analysis of the microvasculature and the assessment of angiogenesis have significant prognostic value in various diseases, including cancer. The search for invasion into the blood and lymphatic vessels and the assessment of angiogenesis are important aspects of oncological diagnosis. These features determine the prognosis and aggressiveness of the tumor. Traditional manual evaluation methods are time consuming and subject to inter-observer variability. Blood vessel detection is a perfect task for artificial intelligence, which is capable of rapid analyzing thousands of tissue structures in whole slide images. The development of computer vision solutions requires the segmentation of tissue regions, the extraction of features and the training of machine learning models. In this review, we focus on the methodologies employed by researchers to identify blood vessels and vascular invasion across a range of tumor localizations, including breast, lung, colon, brain, renal, pancreatic, gastric and oral cavity cancers. Contemporary models herald a new era of computational pathology in morphological diagnostics.

Laser soldering is a current biophotonic technique for the surgical recovery of the integrity of soft tissues. This technology involves the use of a device providing laser exposure to the cut edges of the wound with a solder applied. The proposed solder consisted of an aqueous dispersion of biopolymer albumin (25 wt.%), single-walled carbon nanotubes (0.1 wt.%) and exogenous indocyanine green chromophore (0.1 wt.%). Under laser exposure, the dispersion transforms into a nanocomposite due to the absorption of radiation and its conversion into heat. The nanocomposite is a frame structure of carbon nanotubes in a biopolymer matrix, which provides adhesion of the wound edges and the formation of a strong laser weld. A new laser device based on a diode laser (808 nm) has been developed to implement the method. The device has a temperature feedback system based on a bolometric infrared matrix sensor. The system determines the hottest area of the laser weld and adjusts the current supplied to the diode laser to maintain the preset laser heating temperature. The laser soldering technology made it possible to heal linear defects (cuts) in the skin of laboratory animals (rabbits) without the formation of a fibrotic scar compared to the control (suture material). The combined use of a biopolymer nanocomposite solder and a laser device made it possible to achieve a tensile strength of the laser welds of 4 ± 0.4 MPa. The results of the experiment demonstrated that the addition of single-walled carbon nanotubes to the solder composition leads to an increase in the ultimate tensile strength of the laser welds by 80%. The analysis of regenerative and morphological features in the early stages (1–3 days) after surgery revealed small wound gaps, a decrease in inflammation, the absence of microcirculatory disorders and an earlier epithelization of laser welds compared to the control. On the 10th day after the surgical operation, the laser weld was characterized by a thin cosmetic scar and a continuous epidermis covering the defect. An immunohistochemical analysis proved the absence of myofibroblasts in the area of the laser welds.

The crustacean processing industry produces large quantities of waste by-products (up to 70%). Such wastes could be used as raw materials for producing chitosan, a polysaccharide with a unique set of biochemical properties. However, the preparation methods and the long-term stability of chitosan-based products limit their application in biomedicine. In this study, different scale structures, such as aggregates, photo-crosslinked films, and 3D scaffolds based on mechanochemically-modified chitosan derivatives, were successfully formed. Dynamic light scattering revealed that aggregation of chitosan derivatives becomes more pronounced with an increase in the number of hydrophobic substituents. Although the results of the mechanical testing revealed that the plasticity of photo-crosslinked films was 5–8% higher than that for the initial chitosan films, their tensile strength remained unchanged. Different types of polymer scaffolds, such as flexible and porous ones, were developed by laser stereolithography. In vivo studies of the formed structures showed no dystrophic and necrobiotic changes, which proves their biocompatibility. Moreover, the wavelet analysis was used to show that the areas of chitosan film degradation were periodic. Comparing the results of the wavelet analysis and X-ray diffraction data, we have concluded that degradation occurs within less ordered amorphous regions in the polymer bulk.

Mature hypertrophic scars (HSs) remain a challenging clinical problem, particularly due to the absence of biologically relevant experimental models as a standard rabbit ear HS model only reflects an early stage of scarring. The current study aims to adapt this animal model for simulation of mature HS by validating the time of the scar stabilization using qualitative and quantitative criteria. The full-thickness skin and perichondrium excision wounds were created on the ventral side of the rabbit ears. The tissue samples were studied on post-operation days (PODs) 30, 60, 90 and 120. The histopathological examination and morphometry were applied in parallel with biochemical analysis of protein and glycosaminoglycans (GAGs) content and amino acid composition. The supramolecular organization of collagen was explored by differential scanning calorimetry. Four stages of the rabbit ear HS maturation were delineated and attributed with the histolomorphometrical and physicochemical parameters of the tissue. The experimental scars formed in 30 days but stabilized structurally and biochemically only on POD 90–120. This evidence-based model can be used for the studies and testing of new treatments of the mature HSs.