Soft and Hard Tissue Integration around Percutaneous Bone-Anchored Titanium Prostheses: Toward Achieving Holistic Biointegration.

A holistic biointegration of percutaneous bone-anchored metallic prostheses with both hard and soft tissues dictates their longevity in the human body. While titanium (Ti) has nearly solved osseointegration, soft tissue integration of percutaneous metallic prostheses is a perennial problem. Unlike the firm soft tissue sealing in biological percutaneous structures (fingernails and teeth), foreign body response of the skin to titanium (Ti) leads to inflammation, epidermal downgrowth and inferior peri-implant soft tissue sealing. This review discusses various implant surface treatments/texturing and coatings for osseointegration, soft tissue integration, and against bacterial attachment. While surface microroughness by SLA (sandblasting with large grit and acid etched) and porous calcium phosphate (CaP) coatings improve Ti osseointegration, smooth and textured titania nanopores, nanotubes, microgrooves, and biomolecular coatings encourage soft tissue attachment. However, the inferior peri-implant soft tissue sealing compared to natural teeth can lead to peri-implantitis. Toward this end, the application of smart multifunctional bioadhesives with strong adhesion to soft tissues, mechanical resilience, durability, antibacterial, and immunomodulatory properties for soft tissue attachment to metallic prostheses is proposed.

Evaluation of dynamics of immune responses and protective efficacy in piglets immunized with an inactivated porcine reproductive and respiratory syndrome vaccine candidate.

Porcine Reproductive and Respiratory Syndrome (PRRS) is an important viral disease of swine that causes significant mortality in piglets and production losses in adult pigs. In this study, we investigated the protective efficacy of an inactivated PRRS virus vaccine candidate and evaluated the differences in PRRSV specific anamnestic response in piglets when challenged with live PRRSV at two different intervals post-immunization. Six-week-old piglets were immunized intramuscularly with an inactivated, Montanide ISA-206 adjuvanted Indian PRRSV isolate, followed by a booster dose at 21 days post-immunization. Homologous live PRRS virus challenge was done on 60 and 180 days post-booster (dpb). We assessed humoral and cell-mediated immune responses at various intervals post-immunization and after challenge. Viraemia, virus shedding in nasal secretions and lung lesion scores were studied to assess the efficacy of the vaccine candidate. All the immunized pigs developed PRRSV-specific antibodies upon booster dose administration. Neutralizing antibody (NA) titres before challenge, in most animals, ranged between 0 and 4. Potentially protective NA titre of 8 was observed in serum of seven out of the 12 immunized piglets after challenge, across the immunized groups. A significant increase in the mean T-helper, T-cytotoxic, memory or activated T-helper and NK cell populations was observed in immunized piglets challenged at 180 dpb, from 4 to 11 dpc, 5 to 11 dpc, 5 to 7 dpc and 6 to 11 dpc, respectively as compared to the challenge controls. Protective efficacy of the inactivated PRRSV antigen against the homologous virus challenge was evidenced by earlier onset of PRRSV specific virus neutralizing antibodies and cell mediated immune responses, reduced viremia, nasal virus shedding and severity of lung lesions in immunized piglets as compared to unimmunized controls post-challenge. Our results indicated that the inactivated PRRSV antigen elicited better virus specific anamnestic immune responses in piglets when challenged at six months after the single booster dose, due to age related increase in antigen-specific memory T helper cell responses, as compared to those challenged at 2 months post booster.