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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4137170","sourcedb":"PMC","sourceid":"4137170","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4137170","text":"Introduction\nThe screw type metal implant is widely used in orthopedic, dental, plastic, and maxillofacial surgery. As the number of elderly people has increased, the rate of dental implantation has risen and surgery for patients that have poor bone stock has also been increased. Osseointegration of a metal implant is greatly influenced by the quality of the host bone, and it can be negatively affected by previous radiation therapy or infection, smoking, bone defects, osteoporosis, etc., thereby endangering the survival of the implant [1–4]. For patients with bone defect or poor bone stock, successful dental implant surgery could increase the bone quantity and quality of the implantation site, thereby improving the osseointegration. Therefore, methods to strengthen osseointegration that include implantation of a growth factor to promote bone healing are currently of considerable interest.\nRecombinant human bone morphogenetic protein-2 (rhBMP-2), a member of the transforming growth factor beta superfamily, has been widely studied as a treatment for bone healing due to its excellent osteoinductivity. Growth factors like rhBMP-2 can be delivered to bone defects by several delivery vehicles, including ceramics, polymers, and composites. For dental implant fixation on the implantation site in patients with bone defect or poor bone quality an injectable rhBMP-2 carrier is needed.\nInorganic carriers, such as a tricalcium phosphate (TCP) microsphere have the advantage of being structurally similar to bone, but they also have the disadvantage of being difficult to mold to the shape of a defect; they also have difficulty maintaining strong cohesion [5]. In contrast, many natural polymers have the advantages of being biocompatible, biodegradable, and soluble in physiologic fluids; however, natural polymers derived from animals have risks in terms of immunogenicity or pathogen transmission [6]. These limitations have been overcome by using composites that combine the advantages of the ceramic vehicles, such as osteoconductivity, and the advantages of the natural polymer families, which are moldable and have biodegradable characteristics [7].\nHyaluronic acid (HA) is one of the major components of the extracellular matrix (ECM) and it is found in all the connective tissues of the body. It is a naturally-derived, linear, high molecular weight polymer with viscoelastic properties [8]. HA is an important element that functions in major biological processes, such as tissue organization, wound healing, angiogenesis, and remodeling in skeletal biology [9–12]. In addition, HA is anionic and therefore capable of forming ionic bonds with cationic growth factors like rhBMPs, which is of significance for clinical applications [13]. In addition, HA is injectable, plays a role as an rhBMP-2 carrier, and has the advantage of requiring no premixing during the surgical operation [14]. Although HA hydrogel has the disadvantage of being too weak to hold mechanical loading, it helps increase loading-bearing prosperity through chemical modification and cross-linking. Other natural polymers with potential use in rhBMP delivery, such as gelatin, dextran, and fibrin, are limited by their insufficient mechanical strengths [15].\nInorganic materials used as rhBMP-2 delivery vehicles include β-TCP, which has rhBMP-2-binding activity and which is a useful carrier of rhBMP-2 because of its osteoconductivity and its rapid resorption in the body [5]. One study reported that it recovered a bone defect faster than an autologous bone graft due to carrier characteristics that aided the sustained release of rhBMP-2 in the bone defect [16].\nThe cross-linked hyaluronic acid powder gel used in the present study has the property of absorbing fluids, like blood generated from damaged bone tissue, and it has the advantage that its swelling property (its ability to absorb fluids) and its biocompatibility are not readily changed by the surrounding environment due to its cross-linking. A complex carrier consisting of a mixture of cross-linked powder gel and β-TCP microspheres shows good absorption and it can deliver rhBMP-2 during osteogenesis because its physical characteristics are not appreciably changed; consequently, it promotes bone regeneration around an implant.\nFor effective delivery of rhBMP-2, inorganic β-TCP microspheres were combined with an HA-based powder-like hydrogel, a natural polymer referred to as a “powder-gel” in this study. The aim of the present study was to evaluate if the powder gel composite showed slow release of rhBMP-2 and if it could act as an effective rhBMP-2 carrier for implantation in host bone with a bone defect or poor bone quality. In addition, the rabbit tibia implantation model was used to determine if the powder gel composite loaded with rhBMP-2 could strengthen the osseointegration of a dental implant.","divisions":[{"label":"title","span":{"begin":0,"end":12}},{"label":"p","span":{"begin":13,"end":901}},{"label":"p","span":{"begin":902,"end":1396}},{"label":"p","span":{"begin":1397,"end":2167}},{"label":"p","span":{"begin":2168,"end":3249}},{"label":"p","span":{"begin":3250,"end":3657}},{"label":"p","span":{"begin":3658,"end":4291}}],"tracks":[{"project":"2_test","denotations":[{"id":"24928668-20009601-61779589","span":{"begin":542,"end":543},"obj":"20009601"},{"id":"24928668-23285317-61779589","span":{"begin":542,"end":543},"obj":"23285317"},{"id":"24928668-19767691-61779589","span":{"begin":542,"end":543},"obj":"19767691"},{"id":"24928668-23728522-61779590","span":{"begin":1668,"end":1669},"obj":"23728522"},{"id":"24928668-15897825-61779591","span":{"begin":1912,"end":1913},"obj":"15897825"},{"id":"24928668-17701313-61779592","span":{"begin":2164,"end":2165},"obj":"17701313"},{"id":"24928668-14506240-61779593","span":{"begin":2579,"end":2580},"obj":"14506240"},{"id":"24928668-17965830-61779593","span":{"begin":2579,"end":2580},"obj":"17965830"},{"id":"24928668-2408340-61779593","span":{"begin":2579,"end":2580},"obj":"2408340"},{"id":"24928668-11891291-61779593","span":{"begin":2579,"end":2580},"obj":"11891291"},{"id":"24928668-18507950-61779594","span":{"begin":2752,"end":2754},"obj":"18507950"},{"id":"24928668-16266768-61779595","span":{"begin":3245,"end":3247},"obj":"16266768"},{"id":"24928668-23728522-61779596","span":{"begin":3466,"end":3467},"obj":"23728522"},{"id":"24928668-18194994-61779597","span":{"begin":3653,"end":3655},"obj":"18194994"}],"attributes":[{"subj":"24928668-20009601-61779589","pred":"source","obj":"2_test"},{"subj":"24928668-23285317-61779589","pred":"source","obj":"2_test"},{"subj":"24928668-19767691-61779589","pred":"source","obj":"2_test"},{"subj":"24928668-23728522-61779590","pred":"source","obj":"2_test"},{"subj":"24928668-15897825-61779591","pred":"source","obj":"2_test"},{"subj":"24928668-17701313-61779592","pred":"source","obj":"2_test"},{"subj":"24928668-14506240-61779593","pred":"source","obj":"2_test"},{"subj":"24928668-17965830-61779593","pred":"source","obj":"2_test"},{"subj":"24928668-2408340-61779593","pred":"source","obj":"2_test"},{"subj":"24928668-11891291-61779593","pred":"source","obj":"2_test"},{"subj":"24928668-18507950-61779594","pred":"source","obj":"2_test"},{"subj":"24928668-16266768-61779595","pred":"source","obj":"2_test"},{"subj":"24928668-23728522-61779596","pred":"source","obj":"2_test"},{"subj":"24928668-18194994-61779597","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#a393ec","default":true}]}]}}