Anti-Inflammatory Activity of a Demineralized Bone Matrix: An In Vitro Pilot Study

Demineralized bone matrix (DBM) is commonly used for the reconstruction of bone defects. Early graft consolidation involves a transient inflammatory process. It is, however, unclear whether DBM can modulate this process. To test this possibility, we prepared acid lysates of demineralized ground cortical (DGC) and moldable demineralized fibers (MDF). Murine RAW 264.7 and primary bone marrow macrophages were exposed to acid lysates of DGC and MFD prior to provoking an inflammatory response with lipopolysaccharide (LPS). Similarly, murine ST2 mesenchymal cells were exposed to DGC and MFD with and without interleukin 1β (IL1) and TNFα. We show here that acid lysates of DGC and MFD reduced the expression of IL1 and IL6 in RAW 264.7 macrophages, as determined by RT-PCR and, for IL6, by immunoassay. This response was confirmed with primary macrophages. Likewise, desalted acid lysates exert anti-inflammatory properties on RAW 264.7 cells and in ST2 cells, the forced expression of IL6, inducible nitric oxide synthase (iNOS) and chemokine ligand 5 (CCL5) was reduced. These in vitro findings suggest that DGC and MFD lower the inflammation-induced expression of inflammatory mediators in murine cell-based bioassays.

The risk for complications and reoperations with the use of mega prostheses in bone reconstructions

Background Despite a relatively high risk for complications and reoperations, mega prostheses are considered a useful method for reconstruction of bone defects after tumour resections. The total number of reoperations has not previously been described, and little is known about the complication rate of mega prostheses used for other indications than primary bone tumours. Questions/purposes The current retrospective observational study aimed to describe the patient population treated with mega prostheses at Sahlgrenska University Hospital, Sweden, during 14 consecutive years, reports the complications leading to reoperation and the number and type of reoperations for different kinds of complications, and reports on implant survival. Methods All patients treated with a mega prosthesis, regardless of surgical indication and anatomical location, at Sahlgrenska University Hospital during the period 2006–2019 were identified. The medical records for all patients were reviewed. Data regarding age, sex, diagnosis, site of disease, bone resection length, chemotherapeutical treatment and postoperative complications including infections and oncological outcome, were collected and evaluated. Results One hundred and fourteen patients treated with 116 mega prostheses were included in the study. The predominant indication for primary surgery with a mega prosthesis was sarcoma of either bone or soft tissue (53.5% of the patients). In total 51 prostheses (44%) did not require any reoperation after the primary surgery. The most common reason for reoperation was infection (22%) followed by soft tissue failure (13%). The risk for prosthetic infection was significantly higher in the group of patients operated due to sarcoma compared with all other indications for surgery regardless of surgical site (p = 0.004). Conclusion The study reveals a total reoperation rate of 56% after reconstructive surgery using mega prostheses. Despite the high reoperation rates, at the end of the study period, 83% of the patients had still a functioning prosthesis. Therefore, the use of mega prostheses can be considered a reliable method for reconstruction of large bone defects in selected patients. Level of Evidence Level IV, therapeutic study.

Strategies for large bone defect reconstruction after trauma, infections or tumour excision: a comprehensive review of the literature

Large bone defects resulting from musculoskeletal tumours, infections, or trauma are often unable to heal spontaneously. The challenge for surgeons is to avoid amputation, and provide the best functional outcomes. Allograft, vascularized fibular or iliac graft, hybrid graft, extracorporeal devitalized autograft, distraction osteogenesis, induced-membrane technique, and segmental prostheses are the most common surgical strategies to manage large bone defects. Given its optimal osteogenesis, osteoinduction, osteoconduction, and histocompatibility properties, along with the lower the risk of immunological rejection, autologous graft represents the most common used strategy for reconstruction of bone defects. However, the choice of the best surgical technique is still debated, and no consensus has been reached. The present study investigated the current reconstructive strategies for large bone defect after trauma, infections, or tumour excision, discussed advantages and disadvantages of each technique, debated available techniques and materials, and evaluated complications and new perspectives.

A clinical study on bone defect reconstruction and functional recovery in benign bone tumors of the lower extremity, treated by bone marrow mesenchymal stem cell rapid screening–enrichment–composite system

Background With the development of medical technology, credible options for defect reconstructions after the resection of benign bone tumors of the lower extremities have become a high priority. As the current reconstructive methods commonly used in clinical practice have some flaws, new methods of reconstruction need to be explored. We aimed to prepare a new kind of bioactive scaffold for the repair of bone defects through a stem cell rapid screening–enrichment–composite technology system developed by our team. Furthermore, we aimed to investigate the curative effects of these bioactive scaffolds. Methods Firstly, cell count, trypan blue exclusion rate, and ALP staining were used to evaluate changes in enrichment efficiency, cell activity, and osteogenic ability before and after enrichment. Then, the scaffolds were placed under the skin of nude mice to verify their osteogenic effects in vivo. Finally, the scaffolds were used for the reconstruction of bone defects after operations for benign bone tumors in a patient’s lower limb. The healing status of the defect site at 1 and 3 months was assessed by X-ray, and the Musculoskeletal Tumor Society (MSTS) score was applied to reflect the recovery of patient limb function. Results The system effectively enriched stem cells without affecting the activity and osteogenic abilities of the bone marrow mesenchymal stem cells (BMSCs). Meanwhile, the bioactive scaffolds obtained better osteogenic effects. In patients, the active scaffolds showed better bone integration and healing status, and the patients also obtained higher MSTS scores at 1 and 3 months after surgery. Conclusion As a new technique, the rapid screening–enrichment–composite technology of stem cells demonstrates a better therapeutic effect in the reconstruction of bone defects after surgery for benign bone tumors of the lower extremities, which will further improve patient prognosis.

The Role of Modified Chitosan in Bone Engineering in Diabetes Mellitus: Analytical Review

The review is devoted to the state of the problem during the reconstruction of bone defects in the maxillofacial region, topical issues of the mechanisms of biopolymers action, mainly chitosan, during stimulation of angiogenesis and osteogenesis under conditions of the formation of bone cavities of critical size in the maxillofacial area, as well as under conditions of the development of an inflammatory process with Mellitus diabetes. In the analysis of research papers, the international information bases Web of Science, Scopus, PMC free article, PubMed, Google Scholar were used, mainly over the past 12 years. The main emphasis in the scientific review is placed on the points of application of the chitosan biopolymer in the implementation of already known signaling pathways for the regulation of osteogenesis. Studies have shown that chitosan, as an independent polymer, and especially chitosan copolymers, play an important role in the regulation of osteoblastogenesis and angiogenesis, reducing the osteoclastic response, preventing osteomalacia of the alveolar ridge, accelerating the formation of a new well-vascularized bone.

A Clinical Study on Bone Defect Reconstruction and Functional Recovery in Benign Bone Tumors of the Lower Extremity, Treated by Bone Marrow Mesenchymal Stem Cell Rapid Screening–enrichment–composite System

Background: With the development of medical technology, credible options for defect reconstructions after the resection of benign bone tumors of the lower extremities has become a high priority. As the current reconstructive methods commonly used in clinical practice have some flaws, new methods of reconstruction need to be explored. We aimed to prepare a new kind of bioactive scaffold for the repair of bone defects through a stem cell rapid screening–enrichment–composite technology system developed by our team. Furthermore, we aimed to investigate the curative effects of these bioactive scaffolds. Methods: Firstly, cell count, trypan blue exclusion rate and ALP staining were used to evaluate changes in enrichment efficiency, cell activity and osteogenic ability before and after enrichment. Then, the scaffolds were placed under the skin of nude mice to verify their osteogenic effects in vivo. Finally, the scaffolds were used for the reconstruction of bone defects after operations for benign bone tumors in a patient’s lower limb. The healing status of the defect site at 1 and 3 months was assessed by X-ray and the Musculoskeletal Tumor Society (MSTS) score was applied to reflect the recovery of patient limb function. Results: The system effectively enriched stem cells without affecting the activity and osteogenic abilities of the bone marrow mesenchymal stem cells (BMSCs). Meanwhile, the bioactive scaffolds obtained better osteogenic effects. In patients, the active scaffolds showed better bone integration and healing status, and the patients also obtained higher MSTS scores at 1 and 3 months after surgery. Conclusion: As a new technique, the rapid screening–enrichment–composite technology of stem cells demonstrates a better therapeutic effect in the reconstruction of bone defects after surgery for benign bone tumors of the lower extremities, which will further improve patient prognosis.