de Moraes Marcondes Geissiane, Paretsis Nicole Fidalgo, da Silva Danielle Cristinne Baccarelli, de Souza Anderson Fernando, Rego Mario Antônio Ferraro, da Silva Grazieli Cristina Monteiro, Fülber Joice, Corrêa Luciana, Friedrichsdorf Simone Peixe, de Guzzi Plepis Ana Maria, da Conceição Amaro Martins Virginia, Cortopassi Silvia Renata Gaido, do Valle De Zoppa André Luis
Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ-USP), São Paulo, SP, Brazil.
Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ-USP), São Paulo, SP, Brazil.
J Biomed Mater Res B Appl Biomater. 2025 Jan;113(1):e35523. doi: 10.1002/jbm.b.35523.
Comminuted fractures associated with tissue loss can adversely affect bone regeneration. Biomaterials enriched with mesenchymal stem cells (MSCs) employed for supporting osteosynthesis and potentiating osteoconduction are necessary to fill these bone defects. Natural compound biomaterials, similar to bone tissue, have been extensively tested in animal models for clinical use. Bone tissue engineering studies have used critical-size defects in ovine tibia monitored by imaging and histological examinations to evaluate the regenerative process. This study aimed to monitor the regenerative process in ovine tibial defects with or without chitosan, carbon nanotubes, or hydroxyapatite biomaterials, enriched or not enriched with MSCs. A 3-cm ostectomy was performed in 18 female Suffolk sheep. A 10-hole 4.5 mm narrow locking compression plate was used for osteosynthesis. The animals were randomly divided into three groups (n = 6): control (CON); defects filled with chitosan, carbon nanotubes, and hydroxyapatite biomaterial (BIO); and the same biomaterial enriched with bone marrow MSCs (BIO + CELL). The animals were evaluated monthly using radiographic examinations until 90 postoperative days, when they were euthanized. The limbs were subjected to micro-computed tomography (micro-CT), and bone specimens were subjected to histological evaluations. The radiographic examinations revealed construction stability without plate deviation, fracture, or bone lysis. Micro-CT evaluation demonstrated a difference in bone microarchitecture between the CON and biomaterial treatment groups (BIO and BIO + CELL). In the histological evaluations, the CON group did not demonstrate bone formation, and in the treatment groups (BIO and BIO + CELL), biocompatibility with sheep tissue was noted, and bone formation with trabeculae interspersed with remnants of the biomaterial was observed, with no differences between the groups. In conclusion, biomaterials present osteoconduction with beneficial characteristics for filling bone-lost fractures, and MSCs did not interfere with bone formation.
伴有组织缺损的粉碎性骨折会对骨再生产生不利影响。为支持骨合成和增强骨传导而使用的富含间充质干细胞（MSC）的生物材料对于填补这些骨缺损是必要的。与骨组织相似的天然复合生物材料已在动物模型中进行了广泛的临床应用测试。骨组织工程研究利用绵羊胫骨的临界尺寸缺损，通过影像学和组织学检查来监测再生过程。本研究旨在监测有或没有壳聚糖、碳纳米管或羟基磷灰石生物材料（无论是否富含MSC）的绵羊胫骨缺损的再生过程。对18只雌性萨福克绵羊进行了3厘米的骨切除术。使用一块10孔4.5毫米窄锁定加压钢板进行骨合成。动物被随机分为三组（n = 6）：对照组（CON）；缺损处填充壳聚糖、碳纳米管和羟基磷灰石生物材料的组（BIO）；以及填充相同生物材料并富含骨髓MSC的组（BIO + CELL）。每月对动物进行放射学检查，直至术后90天，然后对其实施安乐死。对四肢进行显微计算机断层扫描（micro-CT），并对骨标本进行组织学评估。放射学检查显示结构稳定，无钢板移位、骨折或骨质溶解。Micro-CT评估表明，CON组与生物材料治疗组（BIO和BIO + CELL）之间的骨微结构存在差异。在组织学评估中，CON组未显示骨形成，而在治疗组（BIO和BIO + CELL）中，观察到与绵羊组织的生物相容性，以及有小梁并夹杂生物材料残余物的骨形成，两组之间无差异。总之，生物材料具有骨传导性，对于填补骨缺损骨折具有有益特性，并且MSC不干扰骨形成。
