An immunologically active, adipose-derived extracellular matrix biomaterial for soft tissue reconstruction: concept to clinical trial

Soft tissue reconstruction remains an intractable clinical challenge as current surgical options and synthetic implants may produce inadequate outcomes. Soft tissue deficits may be surgically reconstructed using autologous adipose tissue, but these procedures can lead to donor site morbidity, require multiple procedures, and have highly variable outcomes. To address this clinical need, we developed an “off-the-shelf” adipose extracellular matrix (ECM) biomaterial from allograft human tissue (Acellular Adipose Tissue, AAT). We applied physical and chemical processing methods to remove lipids and create an injectable matrix that mimicked the properties of lipoaspirate. Biological activity was assessed using cell migration and adipogenesis assays. Characterization of regenerative immune properties in a murine muscle injury model revealed that allograft and xenograft AAT induced pro-regenerative CD4+ T cells and macrophages with xenograft AAT additionally attracting eosinophils secreting interleukin 4 (Il4). In immunocompromised mice, AAT injections retained similar volumes as human fat grafts but lacked cysts and calcifications seen in the fat grafts. The combination of AAT with human adipose-derived stem cells (ASCs) resulted in lower implant volumes. However, tissue remodeling and adipogenesis increased significantly in combination with ASCs. Larger injected volumes of porcine-derived AAT demonstrated biocompatibility and greater retention when applied allogeneicly in Yorkshire cross pigs. AAT was implanted in healthy volunteers in abdominal tissue that was later removed by elective procedures. AAT implants were well tolerated in all human subjects. Implants removed between 1 and 18 weeks demonstrated increasing cellular infiltration and immune populations, suggesting continued tissue remodeling and the potential for long-term tissue replacement.

The Role of Microglial Phagocytosis in Ischemic Stroke

Microglia are the resident immune cells of the central nervous system that exert diverse roles in the pathogenesis of ischemic stroke. During the past decades, microglial polarization and chemotactic properties have been well-studied, whereas less attention has been paid to phagocytic phenotypes of microglia in stroke. Generally, whether phagocytosis mediated by microglia plays a beneficial or detrimental role in stroke remains controversial, which calls for further investigations. Most researchers are in favor of the former proposal currently since efficient clearance of tissue debris promotes tissue reconstruction and neuronal network reorganization in part. Other scholars propose that excessively activated microglia engulf live or stressed neuronal cells, which results in neurological deficits and brain atrophy. Upon ischemia challenge, the microglia infiltrate injured brain tissue and engulf live/dead neurons, myelin debris, apoptotic cell debris, endothelial cells, and leukocytes. Cell phagocytosis is provoked by the exposure of “eat-me” signals or the loss of “don’t eat-me” signals. We supposed that microglial phagocytosis could be initiated by the specific “eat-me” signal and its corresponding receptor on the specific cell type under pathological circumstances. In this review, we will summarize phagocytic characterizations of microglia after stroke and the potential receptors responsible for this programmed biological progress. Understanding these questions precisely may help to develop appropriate phagocytic regulatory molecules, which are promoting self-limiting inflammation without damaging functional cells.

Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects

Articular cartilage is a highly organized tissue that has a limited ability to heal. Tissue engineering is actively exploited for joint tissue reconstruction in numerous cases of articular cartilage degeneration associated with trauma, arthrosis, rheumatoid arthritis, and osteoarthritis. However, the optimal scaffolds for cartilage repair are not yet identified. Here we have directly compared five various scaffolds, namely collagen-I membrane, collagen-II membrane, decellularized cartilage, a cellulose-based implant, and commercially available Chondro-Gide® (Geistlich Pharma AG, Wolhusen, Switzerland) collagen membrane. The scaffolds were implanted in osteochondral full-thickness defects, formed on adult Wistar rats using a hand-held cutter with a diameter of 2.0 mm and a depth of up to the subchondral bone. The congruence of the articular surface was almost fully restored by decellularized cartilage and collagen type II-based scaffold. The most vivid restoration was observed 4 months after the implantation. The formation of hyaline cartilage was not detected in any of the groups. Despite cellular infiltration into scaffolds being observed in each group except cellulose, neither chondrocytes nor chondro-progenitors were detected. We concluded that for restoration of hyaline cartilage, scaffolds have to be combined either with cellular therapy or morphogens promoting chondrogenic differentiation.

Obtaining Biocompatible Porous Composite Material Based on Zinc-Modified Hydroxyapatite and Lactide-Glycolide Copolymer

The development of surgery in the field of bone tissue reconstruction provides a stable demand for new materials for implants. Of particular interest are materials based on hydroxyapatite, which are close in chemical composition to the elemental composition and structure of bone and have similar biologically active properties. In this work, the regularities of the formation of new composite materials based on a zinc-modified hydroxyapatite framework coated with a copolymer of lactide and glycolide were revealed for the first time. The aim of this work was to obtain porous composite materials based on zinc-modified hydroxyapatite and a copolymer of lactide and glycolide with properties suitable for use as a material for bone implants. The phase and elemental composition of the composites was studied by infrared spectroscopy, X-ray diffraction, and X-ray spectral microanalysis. Regularities have been established between the surface properties and the composition of materials, as well as their biocompatibility, determined using monocytes isolated from human peripheral blood. The antibacterial activity of the materials against gram-positive and gram-negative bacteria was determined.

Soft-tissue coverage for wound complications following total elbow arthroplasty

Background: In patients with total elbow arthroplasty (TEA), the soft-tissue around the elbow can be vulnerable to soft-tissue complications. This study aims to assess the outcomes after soft-tissue reconstruction following TEA. Methods: We retrospectively included nine adult patients who underwent soft-tissue reconstruction following TEA. Demographic data and disease characteristics were collected through medical chart reviews. Additionally, we contacted all four patients that were alive at the time of the study by phone to assess any current elbow complications. Local tissue rearrangement was used for soft-tissue reconstruction in six patients, and a pedicle flap was used in three patients. The median follow-up period was 1.3 years (range, 6 months–14.7 years).Results: Seven patients (78%) underwent reoperation. Four patients (44%) had a reoperation for soft-tissue complications, including dehiscence or nonhealing of infected wounds. Five patients (56%) had a reoperation for implant-related complications, including three infections and two peri-prosthetic fractures. At the final follow-ups, six patients (67%) achieved successful wound healing and two patients had continued wound healing issues, while two patients had an antibiotic spacer in situ and one patient underwent an above-the-elbow amputation. Conclusions: This study reports a complication rate of 78% for soft-tissue reconstructions after TEA. Successful soft-tissue healing was achieved in 67% of patients, but at the cost of multiple surgeries. Early definitive soft-tissue reconstruction could prove to be preferable to minor interventions such as irrigation, debridement, and local tissue advancement, or smaller soft-tissue reconstructions using local tissue rearrangement or a pedicled flap at a later stage.