OBJECTIVE: To describe the experience of a single level 1 trauma center in the management of blunt splenic injuries (BSI).
METHODS: This is a retrospective study with Institutional Review Board approval. The medical records of 450 patients with BSI treated between January 2016 and December 2022 were reviewed. Seventy-two patients were treated with splenic artery embolization (SAE), met the study criteria, and were eligible for data analysis. Spleen injuries were graded in accordance with the American Association for the Surgery of Trauma Organ Injury Scale. Univariate data analysis was performed, with P < 0.05 considered statistically significant.
RESULTS: The splenic salvage rate was 90.3% (n = 65/72). Baseline demographics were similar between the groups (P > 0.05). Distal embolization with Gelfoam® had similar rates of splenic salvage to proximal embolization with coils (90% vs. 94.1%, P > 0.05). There was no significant difference in the rate of splenic infarction between distal embolization with Gelfoam® (20%, 4/20) and proximal embolization with coils (17.6%, 3/17) (P > 0.05). There was no significant difference in procedure length (68 vs. 75.8 min) or splenic salvage rate (88.5% vs. 92.1%) between proximal and distal embolization (P > 0.05). There was no significant difference in procedure length (69.1 vs. 73.6 min) or splenic salvage rate (93.1% vs. 86.4%) between Gelfoam® and coil embolization (P > 0.05). Combined proximal and distal embolization was associated with a higher rate of splenic abscess formation (25%, 2/8) when compared with proximal (0%, 0/26) or distal (0%, 0/38) embolization alone (P = 0.0003). The rate of asymptomatic and symptomatic splenic infarction was significantly higher in patients embolized at combined proximal and distal locations (P = 0.04, P = 0.01).
CONCLUSIONS: The endovascular management of BSI is safe and effective. The overall splenic salvage rate was 90.3%. Distal embolization with Gelfoam® was not associated with higher rates of splenic infarction when compared with proximal embolization with coils. Combined proximal and distal embolization was associated with a higher incidence of splenic infarction and splenic abscess formation.
CONCLUSIONS: Distal splenic embolization with Gelfoam® is safe and may be beneficial in the setting of blunt splenic trauma.

A major drawback of nanocomposite scaffolds in bone tissue engineering is dimensional shrinkage after the fabrication process. Shrinkage yields gaps between the scaffold and host bone in the defect site and eventually causes failure in osteointegration by micromovement. The present study was conducted using titanium (Ti) mesh and Gelfoam® to prevent radial and axial micromovement, respectively. A critical-sized defect (CSD) was created in the center of the calvarium of Sprague Dawley rats to implant porous polydopamine-laced hydroxyapatite collagen calcium silicate (HCCS-PDA), a novel nanocomposite scaffold. Gelfoam® was applied around the edge of the defect, and then the HCCS-PDA scaffold was inserted in the defect area. Ti mesh was placed between the periosteum and skin right, above the inserted scaffold site. There were two test groups, with a fixture (Gelfoam® and Ti mesh) and without a fixture, each group contained five animals. The rats were sacrificed after three months post-operation. The explanted calvaria underwent micro-CT scanning and a push-out test to quantify osteointegration and mechanical strength between the scaffold and host bone. Histological analysis of undecalcified bone was performed by grinding resin infiltrated calvaria blocks to prepare 10 μm slices. Osteointegration was higher in the group with fixation than without fixation. Movement of the HCCS-PDA scaffold in the gap resulted in diminished osteointegration. With fixation, the movement was inhibited and osteointegration became prominent. Here we present a successful method of preventing axial and radial movement of scaffolds using Gelfoam® and Ti mesh. Applying this fixture, we expect that an HCCS-PDA scaffold can repair CSD more effectively.

Distant organ colonization by cancer cells is the governing step of metastasis. We review in this chapter the modeling and imaging of organ colonization by cancer cells in Gelfoam® histoculture. ANIP 973 lung cancer cells expressing green fluorescent protein (GFP) were injected intravenously into nude mice, whereby they formed brilliantly fluorescing metastatic colonies on the mouse lung. The seeded lung tissue was then excised and incubated in the three-dimensional Gelfoam® histoculture that maintained the critical features of progressive in vivo organ colonization. Tumor progression was continuously visualized by GFP fluorescence of individual cultures over a 52-day period, during which tumor colonies spread throughout the lung. Organ colonization was selective in Gelfoam® histoculture for lung cancer cells to grow on lung tissue, since no growth occurred on histocultured mouse liver tissue. The ability to support selective organ colonization in Gelfoam® histoculture and visualize tumor progression by GFP fluorescence allows the in vitro study of the governing processes of metastasis.

Cell and tissue culture can be performed on different substrates such as on plastic, in Matrigel™, and on Gelfoam®, a sponge matrix. Each of these substrates consists of a very different surface, ranging from hard and inflexible, a gel, and a sponge-matrix, respectively. Folkman and Moscona found that cell shape was tightly coupled to proper gene expression. The flexibility of a substrate is important for cells to maintain their optimal shape. Human osteosarcoma cells, stably expressing a fusion protein of av integrin, and green fluorescent protein (GFP), grew as a simple monolayer without any structure formation on the surface of a plastic dish. When the osteosarcoma cells were cultured within Matrigel, the cancer cells formed colonies but no other structures. When the cancer cells were seeded on Gelfoam®, the cells formed 3-dimensional tissue-like structures. These results indicate that Gelfoam® histoculture, unlike Matrigel™ culture, is true 3-dimensional.

DNA damage repair in response to UVC irradiation was imaged in cancer cells growing in Gelfoam® histoculture. UVC-induced DNA damage repair was imaged with green fluorescent protein (GFP) fused to the DNA damage response (DDR)-related binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells. Three-dimensional Gelfoam® histocultures and confocal imaging enabled 53BP1-GFP nuclear foci to be observed within 1 h after UVC irradiation, indicating the onset of DNA damage repair response. Induction of UV-induced 53BP1-GFP focus formation was limited up to a depth of 40 μm in Gelfoam® histoculture of MiaPaCa-2 cells, indicating this was the depth limit of UVC irradiation.

Gelfoam® histoculture provides a valuable tool for experimental studies of normal and pathological tissue physiology. It allows us to understand cell-cell interactions by mirroring their original spatial relationship within body tissues. Gelfoam® histoculture can be employed to model host-pathogen interactions mimicking in vivo conditions in vitro. In the present chapter, we describe a protocol to process and infect lymphoid tissue explants with HIV and maintain them in Gelfoam® histoculture at the liquid-air interface. The Gelfoam® histocultures with human immunodeficiency virus (HIV) type 1-infected tissues have been used to further understand the biology of early HIV-1 pathogenesis, as well as a novel ex vivo platform to test the efficacy and toxicity of antiviral drugs.

The stem cell marker, nestin, is expressed in the hair follicle, both in cells in the bulge area (BA) and the dermal papilla (DP). Nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells of both the BA and DP have been previously shown to be able to form neurons, heart muscle cells, and other non-follicle cell types. The ability of the nestin-expressing HAP stem cells from the BA and DP to repair spinal cord injury was compared. Nestin-expressing HAP stem cells from both the BA and DP grew very well on Gelfoam®. The HAP stem cells attached to the Gelfoam® within 1 h. They grew along the grids of the Gelfoam® during the first 2 or 3 days. Later they spread into the Gelfoam®. After transplantation of Gelfoam® cultures of nestin-expressing BA or DP HAP stem cells into the injured spinal cord (including the Gelfoam®) nestin-expressing BA and DP cells were observed to be viable over 100 days post-surgery. Hematoxylin and eosin (H&E) staining showed connections between the transplanted cells and the host spine tissue. Immunohistochemistry showed many Tuj1-, Isl 1/2, and EN1-positive cells and nerve fibers in the transplanted area of the spinal cord after BA Gelfoam® or DP Gelfoam® cultures were transplanted to the spine. The spinal cord of mice was injured to effect hind-limb paralysis. Twenty-eight days after transplantation with BA or DP HAP stem cells on Gelfoam® to the injured area of the spine, the mice recovered normal locomotion.

Patient tumors grew in Gelfoam® histoculture with maintenance of tissue architecture, tumor-stromal interaction, and differentiated functions. In this chapter, we review the use of Gelfoam® histoculture to demonstrate proliferation indices of major solid cancer types explanted directly from surgery. Cell proliferation was visualized by histological autoradiography within the cultured tissues after [3H]thymidine incorporation by the proliferating cells. Epilumination polarization microscopy enables high-resolution imaging of the autoradiography of each cell. The histological status of the cultured tissues can be assessed simultaneously with the proliferation status. Carcinomas were observed to have areas of high epithelial proliferation with quiescent stromal cells. Sarcomas have high proliferation of the cancer cells of mesenchymal organ. Normal tissues can also proliferate at high rates. Mean growth fraction index (GFI) was highest for patient tumors with the pure subtype of small-cell lung cancer than other types of lung cancer.

Three-dimensional cell culture and tissue culture (histoculture) is much more in vivo-like than 2D culture on plastic. Three-dimensional culture allows investigation of crucial events in tumor biology such as drug response, proliferation and cell cycle progression, cancer cell migration, invasion, metastasis, immune response, and antigen expression that mimic in vivo conditions. Three-dimensional sponge-matrix histoculture maintains the in vivo phenotype, including the formation of differentiated structures of normal and malignant tissues, perhaps due to cells maintaining their natural shape in a sponge-gel matrix such as Gelfoam®. Sponge-matrix histoculture can also support normal tissues and their function including antibody-producing lymphoid tissue that allows efficient HIV infection, hair-growing skin, excised hair follicles that grow hair, pluripotent stem cells that form nerves, and much more.

We previously developed a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In this model, nascent blood vessels selectively express GFP. We also previously showed that osteosarcoma cells promote angiogenesis in this assay. We have also previously demonstrated the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R) can inhibit or regress all tested tumor types in mouse models. The aim of the present study was to determine if S. typhimurium A1-R could inhibit osteosarcoma angiogenesis in the in vivo Gelfoam® color-coded imaging assay.
Gelfoam® was implanted subcutaneously in ND-GFP nude mice. Skin flaps were made 7 days after implantation and 143B-RFP human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the implanted Gelfoam. After establishment of tumors in the Gelfoam®, control-group mice were treated with phosphate buffered saline via tail-vein injection (iv) and the experimental group was treated with S. typhimurium A1-R iv Skin flaps were made at day 7, 14, 21, and 28 after implantation of the Gelfoam® to allow imaging of vascularization in the Gelfoam® using a variable-magnification small-animal imaging system and confocal fluorescence microscopy.
Nascent blood vessels expressing ND-GFP extended into the Gelfoam® over time in both groups. However, the extent of nascent blood-vessel growth was significantly inhibited by S. typhimurium A1-R treatment by day 28.
The present results indicate S. typhimurium A1-R has potential for anti-angiogenic targeted therapy of osteosarcoma.