Many surgeries are complicated by the need to anastomose, or reconnect, micron-scale vessels. Although suturing remains the gold standard for anastomosing vessels, it is difficult to place sutures correctly through collapsed lumen, making the procedure prone to failure. Here, we report a multi-phase transitioning peptide hydrogel that can be injected into the lumen of vessels to facilitate suturing. The peptide, which contains a photocaged glutamic acid, forms a solid-like gel in a syringe and can be shear-thin delivered to the lumen of collapsed vessels (where it distends the vessel), and the space between two vessels (where it is used to approximate the vessel ends). Suturing is performed directly through the gel. Light is used to initiate the final gel-sol phase transition that disrupts the hydrogel network, allowing the gel to be removed and blood flow to resume. This gel adds a new tool to the armamentarium for micro- and supermicrosurgical procedures.

Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E-and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E-and P-selectin in the skin holds potential to significantly prolong limb allograft survival.

This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN-LEW) (n = 4) hindlimb transplants were performed and assessed for neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic nerve cut-and-repair and treated with either local or systemic injection of MSCs had significant improvement in the speed of recovery of compound muscle action potential amplitudes and axon counts when compared with negative controls. Similarly, rats undergoing allogeneic hindlimb transplants treated with local injection of MSCs exhibited significantly increased axon counts. Similarly, systemic MSC treatment resulted in improved nerve regeneration following allogeneic hindlimb transplants. Systemic administration had a more pronounced effect on electromotor recovery while local injection was more effective at increasing fiber counts, suggesting different targets of action. Local and systemic MSC injections significantly improve the pace and degree of nerve regeneration after nerve injury and hindlimb transplantation.

Summary Mild skin rejection is a common observation in reconstructive transplantation. To enlighten the role of this inflammatory reaction we investigated markers for cellular and antibody mediated rejection, adhesion molecules and tolerance markers. Forty‐seven skin biopsies (rejection grade I) of human hand allografts were investigated by immunohistochemistry (CD3, CD4, CD8, CD20, CD68, C4d, LFA‐1, ICAM‐1, E‐selectin, P‐selectin, VE‐cadherin, HLA‐DR, IDO, and Foxp3). Expression was read with respect to time after transplant. The infiltrate was mainly comprised of CD3+T‐lymphocytes. Among these, CD8+cells were more prominent than CD4+cells. CD20+B‐lymphocytes were sparse and CD68+macrophages were found in some, but not all samples (approximately 10% of the infiltrate). The CD4/CD8‐ratio was increased after the first year. C4d staining was mainly positive in samples at time‐points later than 1 year. Adhesion molecules LFA‐1, ICAM‐1, E‐selectin, P‐selectin, and VE‐cadherin were found upregulated, and for P‐selectin, expression increased with time after transplant. IDO expression was strongest at 3 months–1 year post‐transplant and a tendency toward more Foxp3+ cells at later time points was observed. Mild skin rejection after hand transplantation presents with a T‐cell dominated dermal cell infiltrate and upregulation of adhesion molecules. The role of C4d expression after year one remains to be elucidated.