The perspectives of regenerative medicine are still severely hampered by the host response to biomaterial implantation, despite the robustness of technologies that hold the promise to recover the functionality of damaged organs and tissues. In this scenario, the cellular and molecular events that decide on implant success and tissue regeneration are played at the interface between the foreign body and the host inflammation, determined by innate and adaptive immune responses. To avoid adverse events, rather than the use of inert scaffolds, current state of the art points to the use of immunomodulatory biomaterials and their knowledge-based use to reduce neutrophil activation, and optimize M1 to M2 macrophage polarization, Th1 to Th2 lymphocyte switch, and Treg induction. Despite the fact that the field is still evolving and much remains to be accomplished, recent research breakthroughs have provided a broader insight on the correct choice of biomaterial physicochemical modifications to tune the reaction of the host immune system to implanted biomaterial and to favor integration and healing.

Age-related changes in the immune system may contribute to morbidity and mortality due to decreased resistance to infection and, possibly, certain cancers in the aged. Many studies mostly performed in mice, rats and man but also including monkeys and dogs have established that age-associated immune decline is characterized by decreases in both humoral and cellular responses. The former may be largely a result of the latter, because observed changes both in the B cell germline-encoded repertoire and the age-associated decrease in somatic hypermutation of the B cell antigen receptors are now known to be critically affected by helper T cell aging. As antigen presenting cell (APC) function appears to be well-maintained in the elderly, this review will focus on the T cell. Factors contributing to T cell immunosenescence may include a) altered production of T cell progenitors (stem cell defects, stromal cell defects), b) decreased levels of newly-generated mature T cells (thymic involution), c) aging of resting immune cells, d) disrupted activation pathways in immune cells (stimulation via the T cell receptor for antigen, costimulation, apoptosis control), e) replicative senescence of clonally expanding cells. This review aims to consider the current state of knowledge on the scientific basis for and potential clinical relevance of those factors in immunosenescence in humans. Experiments in other species will be touched upon with the proviso that there are clearly differences between them, especially between humans and rodents, but exactly what those differences are is not completely clear. Given its potential importance and the increasing proportion of elderly people the world over, coupled with the realisation that whereas mortality is decreasing, morbidity may not be decreasing in parallel (1), a better understanding of the causes and impact of immunosenescence may offer the possibility of identifying where prevention or delay of onset, as well as therapeutic intervention, might be beneficial. Amelioration of the effects of dysregulated immune responses in the elderly by replacement therapy, supplementation therapy or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age.

Cytotoxicity assays provide an in vitro evaluation of the lytic activity of NK and T cells against tumors or transformed cells. However, none of these methods allow the recovery of cells or supernatants after the assay. We standardized a microcytotoxicity test using calcein-acetoxymethyl (calcein-AM) dye that requires very small quantities of cells while maintaining the same sensitivity as the traditional⁵¹Cr assay. The assay is applicable to resting as well as activated human effector cells and uses different targets such as human cell lines that are adherent or growing in suspension and resistant or sensitive. The most important feature of the method is the possibility of recovering cells and supernatants for additional analyses such as phenotyping and evaluation of soluble factors.

Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl₂, 10% of autologous thrombin, 10% of a mixture of CaCl₂+ thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl₂, thrombin, and CaCl₂/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl₂/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF-β1that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl₂induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic.

Elbow stiffness is a common complication after elbow trauma. The elbow capsule is often thickened, fibrotic, and contracted at the time of surgical release. The limited studies available suggest that the capsule is contracted because of fibroblast-to-myofibroblast differentiation. We hypothesize that myofibroblasts are absent in normal elbow capsules and in acute trauma and that they are subsequently elevated in patients with posttraumatic elbow contracture. We obtained twenty-one human elbow joint capsules within fourteen days after an elbow fracture and/or dislocation and thirty-four elbow joint capsules in thirty-four patients who had undergone operative release of posttraumatic contractures more than five months after injury. Myofibroblasts in the joint capsules were quantified with use of immunohistochemistry. Alpha-smooth muscle actin was used as a marker for myofibroblasts. Samples were characterized and were scored by an independent pathologist blinded for clinical data. Eleven capsules were associated with the acute phase after trauma (hours to less than seven days), and staining for alpha-smooth muscle actin was negative in all but one capsule. Ten capsules were associated with a later posttraumatic phase with myofibroblasts staining positive for alpha-smooth muscle actin in all but two capsules. Thirty-two long-standing contractures showed a histological pattern consistent with chronic stages of fibrosis, characterized by increased fibroblast-like cell proliferation and higher cellular density of fibroblast-like cells with highly unstructured collagen. Two joint capsules showed an earlier phase of fibrosis. Only two of the long-standing contractures had staining of alpha-smooth muscle actin in fibroblast-like cells; the lack of staining in the other contractures suggested an absence of myofibroblasts. This study presents negative results on the hypothesis that myofibroblast numbers are elevated in long-standing (more than five months) human posttraumatic elbow capsules. The absence of myofibroblasts in long-standing elbow contracture capsules is in contrast to most other studies on human tissue in the literature to date.