Format chain exchange (FORCE) for high-throughput generation of bispecific antibodies in combinatorial binder-format matrices.

Generation of bispecific antibodies (bsAbs) requires a combination of compatible binders in formats that support desired functionalities. Here, we report that bsAb-matrices can be generated by Format Chain Exchange (FORCE), enabling screening of combinatorial binder/format spaces. Input molecules for generation of bi/multi-valent bsAbs are monospecific entities similar to knob-into-hole half-antibodies, yet with complementary CH3-interface-modulated and affinity-tagged dummy-chains. These contain mutations that lead to limited interface repulsions without compromising expression or biophysical properties of educts. Mild reduction of combinations of educts triggers spontaneous chain-exchange reactions driven by partially flawed CH3-educt interfaces resolving to perfect complementarity. This generates large bsAb matrices harboring different binders in multiple formats. Benign biophysical properties and good expression yields of educts, combined with simplicity of purification enables process automation. Examples that demonstrate the relevance of screening binder/format combinations are provided as a matrix of bsAbs that simultaneously bind Her1/Her2 and DR5 without encountering binder or format-inflicted interferences.

Rehabilitation of edentulous jaws with zirconia complete-arch fixed implant-supported prostheses: An up to 4-year retrospective clinical study.

STATEMENT OF PROBLEM: Limited data are available on the clinical outcomes of patients with edentulism treated with zirconia complete-arch fixed implant-supported prostheses (CAFIPs). PURPOSE: The primary purpose of this retrospective clinical study was to study the failure rate of dental implants as well as the fracture rate of zirconia CAFIPs. The secondary purpose was to study the survival outcomes of patients with edentulism treated with zirconia CAFIPs as well as the rate of technical complications. MATERIAL AND METHODS: This retrospective clinical study from private practice included 128 patients rehabilitated between January 1, 2013, and December 31, 2016, with 1072 implants supporting 191 zirconia CAFIPs for single-jaw as well as double-jaw rehabilitations. All zirconia prostheses were of 1-piece design and were veneered with feldspathic porcelain only at the gingival region and therefore considered as predominantly monolithic. Additionally, all prostheses were bonded to implant manufacturer's titanium cylinders that provided an intimate contact with the implants. The primary outcome measures were implant failure rate and prosthesis fracture rate. The secondary outcome measures were prosthodontic treatment survival rate and the incidence of technical complications with respect to monolithic zirconia CAFIPs. Cumulative survival rate (CSR) for implants and prostheses was calculated after a life-table survival analysis. RESULTS: Of the analyzed samples over a 4-year period, at least 288 implants and 49 prostheses had a minimum of 4 years of follow-up. A total of 18 implant failures were noted (13 in maxilla, 5 in mandible), yielding a CSR of 97.6% for implants. One fracture of the zirconia prosthesis was recorded, yielding a CSR of 99.4% for the prostheses over the 4-year period. Another 3 prostheses required remaking because the supporting implants failed, and 1 prosthesis was remade because the lack of passive fit resulted in a CSR of 96.8% for the prosthodontic treatment itself. During the 4-year period, 1 zirconia prosthesis had a technical complication related to the debonding of titanium cylinders, and 2 prostheses had fractured screws, which were resolved successfully. No zirconia prostheses had chipping of the veneered gingival porcelain. CONCLUSIONS: Findings from this retrospective clinical study from private practice showed that prosthodontic treatment of edentulous patients with a 1-piece, complete-arch fixed implant-supported zirconia prosthesis with veneered porcelain restricted to the gingival region had high survival rates for implants and prostheses. Minimal technical complications related to this type of treatment for edentulous jaws and no chipping of the veneered gingival porcelain were encountered.

Survival of 2039 complete arch fixed implant-supported zirconia prostheses: A retrospective study.

STATEMENT OF PROBLEM: Presently, data for the survival of 1-piece complete arch fixed implant-supported zirconia prostheses are limited. PURPOSE: The purpose of this retrospective study was to evaluate the survival outcomes of 1-piece complete arch fixed implant-supported zirconia prostheses fabricated by a single dental laboratory supporting several clinicians. MATERIAL AND METHODS: Outcome data were collected over a 5-year period from a large commercial dental laboratory that fabricated 2039 1-piece complete arch fixed implant-supported monolithic zirconia prostheses. All prostheses were fabricated using the same zirconia system from 1 manufacturer, using standardized protocols. The zirconia prostheses were predominantly monolithic, with veneered porcelain restricted to the gingival region. Because a 5-year warranty against fracture was offered by this dental laboratory, prostheses that were returned to the laboratory for remake because of catastrophic failure (fracture) or technical complications were identified, and data were analyzed using a life table. RESULTS: Of the 2039 zirconia prostheses evaluated, at least 319 prostheses had a minimum of 3 years of clinical service, and 69 prostheses had a minimum of 4 years of clinical service. A total of 6 fractures were reported, resulting in a first-year interval survival rate of 99.8% and a 5-year cumulative survival rate of 99.3%. Six zirconia prostheses were returned to the laboratory during the 5-year period because of technical complications related to the debonding of titanium cylinders, and 3 prostheses were returned because of fracture of the titanium cylinders. No prostheses were returned because of chipping of the veneered gingival porcelain. CONCLUSIONS: Practice-based evidence from this large sample, short-term retrospective study showed that 1-piece complete arch fixed implant-supported zirconia prostheses with veneered porcelain restricted to the gingival region showed a cumulative survival rate of 99.3% in a 5-year period. The technical complication rate related to this type of prosthesis was minimal.