title: Strontium-rich injectable hybrid system for bone regeneration.
abstract: Current challenges in the development of scaffolds for bone regeneration include the engineering of materials that can withstand normal dynamic physiological mechanical stresses exerted on the bone and provide a matrix capable of supporting cell migration and tissue ingrowth. The objective of the present work was to develop and characterize a hybrid polymer–ceramic injectable system that consists of an alginate matrix crosslinked in situ in the presence of strontium(Sr), incorporating a ceramic reinforcement in the form of Sr-rich microspheres. The incorporation of Sr in the microspheres and in the vehicle relies on the growing evidence that Sr has beneficial effects in bone remodeling and in the treatment of osteopenic disorders and osteoporosis. Sr-rich porous hydroxyapatite microspheres with a uniform size and a mean diameter of 555 μm were prepared, and their compression strength and friability tested. A 3.5% (w/v) ultrapure sodium alginate solution was used as the vehicle and its in situ gelation was promoted by the addition of calcium (Ca) or Sr carbonate and Glucone-δ-lactone. Gelation times varied with temperature and crosslinking agent, being slower for Sr than for Ca, but adequate for injection in both cases. Injectability was evaluated using a device employed in vertebroplasty surgical procedures, coupled to a texture analyzer in compression mode. Compositions with 35%w of microspheres presented the best compromise between injectability and compression strength of the system, the force required to extrude it being lower than 100 N.Micro CT analysis revealed a homogeneous distribution of the microspheres inside the vehicle, and a mean inter-microspheres space of 220 μm. DMA results showed that elastic behavior of the hybrid is over the viscous one and that the higher storage modulus was obtained for the 3.5%Alg–35%Sr-HAp-Sr formulation.
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; FMUP - Faculdade de Medicina da Universidade do Porto, Departamento de Cirurgia, Serviço de Ortopedia, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: nsmneves@gmail.com.
authors.forename: Nuno
authors.initials: N
authors.lastname: Neves
authors.affiliation: FCUP - Faculdade de Ciências da Universidade do Porto, Centro de Investigação em Química, Departamento de Química e Bioquímica, Rua do Campo Alegre 1021/1055, 4169-007 Porto, Portugal.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Campos
authors.affiliation: FFUP - Faculdade de Farmácia da Universidade do Porto, Laboratório de Tecnologia Farmacêutica, Departamento de Ciências do Medicamento, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Isabel F
authors.initials: IF
authors.lastname: Almeida
authors.affiliation: FFUP - Faculdade de Farmácia da Universidade do Porto, Laboratório de Tecnologia Farmacêutica, Departamento de Ciências do Medicamento, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Costa
authors.affiliation: FMUP - Faculdade de Medicina da Universidade do Porto, Departamento de Cirurgia, Serviço de Ortopedia, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Abel Trigo
authors.initials: AT
authors.lastname: Cabral
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Mário A
authors.initials: MA
authors.lastname: Barbosa
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; ISEP - Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida 431, 4249-015 Porto, Portugal.
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Ribeiro
mesh_terms: D001851:Bone Diseases, Metabolic / Q000378:metabolism / Q000628:therapy; D001861:Bone Regeneration; D002118:Calcium / Q000737:chemistry; D002516:Ceramics / Q000737:chemistry*; D008863:Microspheres; D013324:Strontium / Q000737:chemistry*
chemical_list: D002118:Calcium; D013324:Strontium
keywords: Alginate; Biomaterials; Hydroxyapatite; Injectable bone substitute; Strontium