Modular and Versatile Spatial Functionalization of Tissue Engineering Scaffolds through Fiber-Initiated Controlled Radical Polymerization.

Native tissues are typically heterogeneous and hierarchically organized, and generating scaffolds that can mimic these properties is critical for tissue engineering applications. By uniquely combining controlled radical polymerization (CRP), end-functionalization of polymers, and advanced electrospinning techniques, a modular and versatile approach is introduced to generate scaffolds with spatially organized functionality. Poly-ε-caprolactone is end functionalized with either a polymerization-initiating group or a cell-binding peptide motif cyclic Arg-Gly-Asp-Ser (cRGDS), and are each sequentially electrospun to produce zonally discrete bilayers within a continuous fiber scaffold. The polymerization-initiating group is then used to graft an antifouling polymer bottlebrush based on poly(ethylene glycol) from the fiber surface using CRP exclusively within one bilayer of the scaffold. The ability to include additional multifunctionality during CRP is showcased by integrating a biotinylated monomer unit into the polymerization step allowing postmodification of the scaffold with streptavidin-coupled moieties. These combined processing techniques result in an effective bilayered and dual-functionality scaffold with a cell-adhesive surface and an opposing antifouling non-cell-adhesive surface in zonally specific regions across the thickness of the scaffold, demonstrated through fluorescent labelling and cell adhesion studies. This modular and versatile approach combines strategies to produce scaffolds with tailorable properties for many applications in tissue engineering and regenerative medicine.

Injectable Pore-Forming Hydrogel Scaffolds for Complex Wound Tissue Engineering: Designing and Controlling Their Porosity and Mechanical Properties.

Traumatic soft tissue wounds present a significant reconstructive challenge. The adoption of closed-circuit negative pressure wound therapy (NPWT) has enabled surgeons to temporize these wounds before reconstruction. Such systems use porous synthetic foam scaffolds as wound fillers at the interface between the negative pressure system and the wound bed. The idea of using a bespoke porous biomaterial that enhances wound healing, as filler for an NPWT system, is attractive as it circumvents concerns regarding reconstructive delay and the need for dressing changes that are features of the current systems. Porous foam biomaterials are mechanically robust and able to synthesize in situ. Hence, they exhibit potential to fulfill the niche for such a functionalized injectable material. Injectable scaffolds are currently in use for minimally invasive surgery, but the design parameters for large-volume expansive foams remain unclear. Potential platforms include hydrogel systems, (particularly superabsorbent, superporous, and nanocomposite systems), polyurethane-based moisture-cured foams, and high internal phase emulsion polymer systems. The aim of this review is to discuss the design parameters for such future biomaterials and review potential candidate materials for further research into this up and coming field.

Managing missed lower extremity compartment syndrome in the physiologically stable patient: A systematic review and lessons from a Level I trauma center.

BACKGROUND: Decompressing an acute lower extremity compartment syndrome salvages muscle and nerve and preserves limb function. However, reperfusion of ischemic tissue causes a systemic insult that can be life threatening. Hence, the management of missed acute lower limb compartment syndrome remains controversial. The aim of this study was to evaluate the literature and, together with our own experience from a Level 1 trauma center, clarify the management of missed compartment syndrome in the physiologically stable patient. METHODS: Pubmed, EMBASE, MEDLINE, the Cochrane database of systematic reviews and the Cochrane central register of controlled trials were searched. Studies were evaluated using the GRADE methodology. In addition, our trauma database was searched (2005 to May 2015) for additional cases, and a multidisciplinary case note review was conducted for all cases identified. This study was registered prospectively on the PROSPERO database (CRD42015026098). RESULTS: Our systematic review yielded 9 studies, including one case-controlled study, 3 case series, and 5 case reports with a total of 57 patients and 64 limbs. Overall, study quality was "very low" with the exception of the case-controlled study, which was "low." Delayed compartment decompression (6-120 hours) resulted in amputation rates of 5 of 24, 8 of 19, 4 of 5, and 2 of 3 limbs. Two patients died of complications associated with late compartment decompression. One compartment syndrome of the buttock was managed nonoperatively. Most surviving limbs exhibited functional deficits.Additionally, our experience comprised 10 cases. Of the six who underwent compartment decompression, the burden of subsequent morbidity included three amputations (one above knee), two complete foot drops, and one episode of severe sepsis. As this experience mirrored the poor outcomes reported in the literature, we managed the four most recent cases nonoperatively. All remain ambulant with incomplete foot drops or limb weakness. CONCLUSION: Surgical decompression of missed acute lower limb compartment syndrome yields an early physiological insult and a high late-amputation rate. Managing selected cases nonoperatively may result in less early morbidity and yield superior long-term results, but the evidence remains sparse and of poor quality. LEVEL OF EVIDENCE: Systematic review, level III.

Prolongation of skin allograft survival after neonatal injection of donor bone marrow and epidermal cells.

Composite-tissue (e.g., hand allograft) allotransplantation is currently limited by the need for immunosuppression to prevent graft rejection. Inducing a state of tolerance in the recipient could potentially eliminate the need for immunosuppression but requires reprogramming of the immunological repertoire of the recipient. Skin is the most antigenic tissue in the body and is consistently refractory to tolerance induction regimens using bone marrow transplantation alone. It was hypothesized that tolerance to skin allografts could be induced in rats by injecting epidermal cells with bone marrow cells during the first 24 hours of life of the recipients. Brown Norway rats (RT1n) served as donors for the epidermal cells, bone marrow cells, and skin grafts. Epidermal cells were injected intraperitoneally and bone marrow cells were injected intravenously into Lewis (RT1l) newborn recipient rats. In control groups, recipients received saline solution with no cells (group I, n = 12), bone marrow cells only (group II, n = 15), or epidermal cells only (group III, n = 15). In the experimental group (group IV, n = 18), recipients received epidermal and bone marrow cells simultaneously. Skin grafts were transplanted from Brown Norway (RT1n) rats to the Lewis (RT1l) rats 8 weeks after cell injections. Skin grafts survived an average of 8.5 days in group I (10 grafts), 9.2 days in group II (12 grafts), and 12 days in group III (14 grafts). Grafts survived 15.5 days (8 to 26 days) in group IV (15 grafts). The difference was statistically significant (p < 0.05). Hair growth was observed in some accepted grafts in group IV but never in the control groups. This is the first report of prolonged survival of skin allografts in a rat model after epidermal and bone marrow cell injections. Survival prolongation was achieved across a major immunological barrier, without irradiation, myeloablation, or immunosuppression. It is concluded that the presentation of skin-specific antigens generated a temporary state of tolerance to the skin in the recipients that could have delayed the rejection of skin allografts.

Experience of an orthoplastic limb salvage team after the Haiti earthquake: analysis of caseload and early outcomes.

BACKGROUND: After the devastating earthquake in Haiti on January 12, 2010, a British orthoplastic limb salvage team was mobilized. The team operated in a suburb of Port-au-Prince from January 20, 2010. This analysis gives an overview of the caseload and early outcomes. METHODS: A retrospective analysis of operative data from the log book was performed from the opening of the facility on January 20, 2010, until March 12, 2010. RESULTS: In total, 348 operations were carried out on 158 patients, at an average of 47 cases per week. Seventy-three percent of the cases were soft-tissue cases and 25 percent were bony or combined soft-tissue and bony cases. The majority of bony procedures (n = 26; 16 percent) and flap procedures (n = 16; 10 percent) took place in the early weeks (weeks 1 through 4). Combined orthoplastic cases accounted for 37 percent of cases (16 of 44) in week 2 but only 7 percent (three of 43) in week 7. General anesthetic cases accounted for 89 percent of cases (39 of 44) in week 2 but only 40 percent (17 of 43) in week 7. Only six patients (4 percent) underwent amputation, but 36 operations (10 percent) dealt with the sequelae of amputation. Sixteen patients (10 percent) suffered complications, including two amputations for failed limb salvage. CONCLUSIONS: This article reports the outcomes of a limb salvage team in the acute response after an earthquake disaster with a favorable amputation rate and highlights the potential benefit of mobilizing this type of team. Detailing the changing caseload over time will allow for more efficient planning in case of a similar future disaster.