Augment Bone Healing Research Articles

Is bone-grafting or bone-healing adjunct always necessary for the treatment of non-union ? Our experience of treating non-unio by primary osteosynthesis in chronically neglected shaft of femure fractures

Non-union of bone is a frightening consequence of fracture management. This condition usually occurs when the body's natural healing process cannot bridge the gap and restore the continuity of the bone. Non-infected non-union can be classified into two main types: Hypertrophic and Atrophic. Our research aims to determine the results after primary osteosynthesis without bone graft or adjuvant in neglected shaft femur fracture aseptic non-unions.We performed a retrospective chart review to include consequative series of neglected shaft of femur fracture non-unions treated by primary osteosynthesis surgery during a span of 3 years from 2020-2022. We excluded cases with partial union, identifiable systemic or external causes of non-union and those belonging to pediatric & elder age groups.We included 13 neglected cases of shaft femur fractures. Out of 13 patients, 7 (53.8%) were males. The mean age was 43 (range 23-55) years, and the mean injury presentation interval was 9 (range 4-18) months. Nine had hypertrophic, 2 had atrophic and 1 had undefinable non-union. At one year follow-up, 12 out of 13 showed completely united fractures with no functional limitation. Only one patient showed delayed union and eventually united Discussion: Treating non-union requires a comprehensive approach tailored to the fracture personality. The original AO principles (1960) of fracture healing remain the mainstay of fracture healing. Besides the gold standard autologus bone graft, many biological agents like BMP are currently available to augment bone healing. However, most of them have failed to provide consistent and promising results when there is an absence of innate osteogenic potential.In our experience, an excellent union rate can be achieved without the use of bone-grafting or bone-healing adjuvants in chronically neglected long bone fractures where no previous surgical attempt was made in absence of systemic and exteral risk factors for non-union.

Organic-inorganic composite of polypropylene fumarate and nanohydroxyapatite as carrier of antibiotics for the treatment of bone infections

Current treatment approaches in clinics to treat the infectious lesions have partial success thus demanding the need for development of advanced treatment modalities. In this study we fabricated an organic-inorganic composite of polypropylene fumarate (PPF) and nanohydroxyapatite (nHAP) by photo-crosslinking as a carrier of two clinically used antibiotics, ciprofloxacin (CIP) and rifampicin (RFP) for the treatment of bone infections. Carboxy terminal-PPF was first synthesized by cis-trans isomerization of maleic anhydride which was then photo-crosslinked using diethylfumarate (DEF) as crosslinker and bis-acylphosphine oxide (BAPO) as photo-initiator under UV lights (P). A composite of PPF and nHAP was fabricated by incorporating 40 % of nHAP in the polymeric matrix of PPF (PH) which was then characterized for different physicochemical parameters. CIP was added along with nHAP to fabricated CIPloaded composite scaffolds (PHC) which was then coated with RFP to synthesize RFP coated CIP-loaded scaffolds (PHCR). It was observed that there was a temporal separation in the in vitro release of two antibiotics after coating PHC with RFP with 80.48 ± 0.40 % release of CIP from PHC and 62.43 ± 0.21 % release of CIP from PHCR for a period of 60 days. Moreover, in vitro protein adsorption was also found to be maximum in PHCR (154.95 ± 0.07 μg/mL) as observed in PHC (75.42 ± 0.06 μg/mL), PH (24.47 ± 0.08 μg/mL) and P alone (4.47 ± 0.02 μg/mL). The scaffolds were also evaluated using in vivo infection model to assess their capacity in reducing the bacterial burden at the infection site. The outcome of this study suggests that RFP coated CIP-loaded PPF composite scaffolds could reduce bacterial burden and simultaneously augment bone healing during infection related fractures.

Современные методы медикаментозной и локальной терапии замедленной консолидации переломов (обзор литературы)

Introduction Management of post-traumatic disorders of bone regeneration continues to be a substantial clinical challenge in orthopaedic trauma. These include refracture, nonunion, delayed consolidation. The purpose is to explore modern methods of treatment of delayed fracture consolidation. Methods The literature search was produced via open access electronic databases of scientific literature PubMed and eLIBRARY. Search depth was 10 years. Results The article presents methods of medication and local therapy for delayed fracture consolidation. The effectiveness of the use of the ossein-hydroxyapatite complex and vitamin D is reported in patients with normalized healing time of a long bone fracture. The findings showed that bisphophonates, denosumab and strontium ranelate can reduce the risk of fractures with no adverse effect on bone healing. There is controversy on the effect of Teriparatide improving fracture healing. This review will envisage the current clinical trials on bone healing augmentation based on bone grafts, bone substitutes, synthetic growth factors, cell therapy and PRP therapy. Local use of bisphosphonates administered either alone or in combination with other agents is of great interest. Bisphosphonates (etidronate) locally applied in combination with lanthanide ions and calcium for animal fractures demonstrated a positive effect on the reparative process. Conclusion The applicability of medication and local therapy is very high in the treatment of patients with delayed fracture consolidation. Despite numerous studies many questions remain unresolved, and there is a need for the investigations. The local use of bisphosphonates was shown to be promising in the management of delayed fracture consolidation.

Decellularized xenogenic bone graft for repair of segmental bone defect in rabbits.

Bone grafting is a preferred treatment option for the healing of large diaphyseal bone defects and is useful in the management of nonunion, delayed union, and tumor resection. To investigate a decellularization protocol of bovine cancellous bone for xenogenic implantation in radial bone defects in rabbits. Bovine bone scaffolds fabricated with various decellularization protocols viz phosphate buffer saline (PBS), 1% sodium dodecyl sulfate (SDS), and rapid freeze and thaw technique. The manufactured scaffolds were characterized by biomechanical testing, histological staining, and scanning electron microscopy. A 10 mm rabbit radius bone defect was repaired with autograft and SDS treated and rapid freeze and thaw in groups A, B, and C respectively. Healing was evaluated by radiography and histopathology at 0, 30, 60, and 90 days. The grafts were also checked for host tissue reaction and incorporation into the defect. The freeze and thaw group showed complete elimination of all cellular nuclei, regular arrangement of collagen fiber, and no significant difference in tensile strength compared to 1% SDS treated and native groups. The in vivo radiographic and histopathological study showed that the rapid freeze and thaw group had complete bridging of the bone gap defect with new bone formation and they were immunologically less reactive compared to group B. The in vitro and in vivo evaluation of the grafts suggested that freeze and thaw technique was most superior to all other techniques for effective decellularization and augmentation of bone healing with better integration of the graft into the host.

Periosteum-Mimicking Tissue-Engineered Composite for Treating Periosteum Damage in Critical-Sized Bone Defects.

The periosteum is an indispensable part of the bone that nourishes the cortical bone and acts as a repertoire of osteoprogenitor cells. Periosteal damage as a result of traumatic injuries, infections, or surgical assistance in bone surgeries is often associated with a high incidence of delayed bone healing (union or nonunion) compounded with severe pain and a risk of a secondary fracture. Developing bioengineered functional periosteal substitutes is an indispensable approach to augment bone healing. In this study, we have developed a biomimetic periosteum membrane consisting of electrospun oxygen-releasing antioxidant polyurethane on collagen membrane (polyurethane-ascorbic acid-calcium peroxide containing fibers on collagen (PUAOCC)). Further, to assist bone formation, we have developed a bioactive inorganic-organic composite cryogel (bioglass-collagen-gelatin-nanohydroxyapatite (BCGH)) as a bone substitute. In an in vitro simulated oxidative stress model, PUAOCC supported the primary periosteal cell survival. Moreover, in an in vivo, critical-sized (5.9 mm × 3.2 mm × 1.50 mm) unicortical rat tibial bone defect, implantation of PUAOCC along with the functionalized BCGH led to significant improvement in bone formation along with periosteal regeneration. The periosteal regeneration was confirmed by expression of periosteum-specific periostin and neuronal regulation-related protein markers. Our study demonstrates the development of a periosteum-mimicking membrane with promising applications to facilitate periosteal regeneration, thus assisting bone formation when used in combination with bone composites and mimicking the natural bone repair process.

Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation.

Bone defects and improper healing of fractures are an increasing public health burden, and there is an unmet clinical need in their successful repair. Gene therapy has been proposed as a possible approach to improve or augment bone healing with the potential to provide true functional regeneration. While large numbers of studies have been performed in vitro or in vivo in small animal models that support the use of gene therapy for bone repair, these systems do not recapitulate several key features of a critical or complex fracture environment. Larger animal models are therefore a key step on the path to clinical translation of the technology. Herein, the current state of orthopedic gene therapy research in preclinical large animal models was investigated based on performed large animal studies. A summary and an outlook regarding current clinical studies in this sector are provided. It was found that the results found in the current research literature were generally positive but highly methodologically inconsistent, rendering a comparison difficult. Additionally, factors vital for translation have not been thoroughly addressed in these model systems, and the risk of bias was high in all reviewed publications. These limitations directly impact clinical translation of gene therapeutic approaches due to lack of comparability, inability to demonstrate non-inferiority or equivalence compared with current clinical standards, and lack of safety data. This review therefore aims to provide a current overview of ongoing preclinical and clinical work, potential bottlenecks in preclinical studies and for translation, and recommendations to overcome these to enable future deployment of this promising technology to the clinical setting.

Stem Cell Therapy in the Management of Fracture Non-Union - Evaluating Cellular Mechanisms and Clinical Progress.

Bone, as a physiological and anatomical construct, displays remarkable intrinsic healing capacity. The overwhelming majority of fractures will heal satisfactorily, if aligned anatomically, compressed and immobilised appropriately. Of the 10% of fractures that do not heal, even under ideal mechanical and biological conditions, further consideration must be given to augment bone healing. Management strategies for non-union pose a significant clinical challenge to the practicing orthopaedic surgeon. Stem cell therapy is beginning to demonstrate significant potential for augmented bone repair in the context of non-union. This review attempts to contextualise the function of stem cells within this clinical setting, reviewing the relevant cellular mechanisms and clinical applications. From evaluating the literature base, there is a lack of high-quality evidence examining the role of mesenchymal stem cells (MSCs) within this research focus. Appropriately designed randomised controlled trials are required to evaluate this research area further, with a view to guiding future treatment options for the practicing orthopaedic surgeon.

Use of Osteobiologics for Fracture Management: The When, What, and How.

Osteobiologics are defined as a group of natural and synthetic materials used to augment bone healing. The selection of the most appropriate osteobiologic from the growing list of available options can be a challenging task. In selecting a material, surgeons should weigh a variety of considerations, including the indication for their use (the when), the most suitable substance (the what), and the correct mode of application (the how). This summary reviews these considerations and seeks to provide the surgeon with a basis for informed clinical evidence-based decision-making in their choice of a successful option.

Bone Morphogenetic Protein in Scaphoid Nonunion: A Systematic Review.

Background Scaphoid nonunion can lead to carpal collapse and osteoarthritis, a painfully debilitating problem. Bone morphogenetic protein (BMP) has been successfully implemented to augment bone healing in other circumstances, but its use in scaphoid nonunion has yielded conflicting results. Case Description The purpose of this study is to assess the outcomes and complications of scaphoid nonunion treated surgically with BMP. Literature Review A literature review of all available journal articles citing the use of BMP in scaphoid nonunion surgery from 2002 to 2019 was conducted. We included studies that used BMP as an adjunct to surgical treatment for scaphoid nonunions in both the primary and revision settings with computed tomography determination of union. Demographic information, dose of BMP, tobacco use, outcomes, and complications were recorded. A total of 21 cases were included from four different studies meeting inclusion criteria. Clinical Relevance The union rates were 90.5% overall, 100% for primary surgeries, and 77.8% for revision surgeries. Five patients (24%) experienced 11 complications, including four cases (19%) of heterotrophic ossification. Use of BMP in scaphoid nonunion surgery resulted in a 90.5% overall union rate but was also associated with complications such as heterotopic ossification. All included studies used BMP to augment bone graft, screw or wire fixation, or a combination of methods. The efficacy of BMP in scaphoid nonunion is unclear, and a sufficiently powered, randomized controlled trial is needed to determine optimal fixation methods, dosing, and morbidity of the use of BMP. Level of Evidence This is a Level IC, therapeutic interventional study.

Simvastatin and Ezetimibe-Loaded Nanofibers Administered Locally to Augment Bone Healing

The article's abstract is not available.

Safety Profile Associated With Calcaneal Autograft Harvesting Using a Reaming Graft Harvester.

Foot and ankle surgery often requires bone healing, whether in elective arthrodesis or trauma. While primary bone healing is possible, the rate of nonunion in foot and ankle surgery remains variable. The addition of autogenous bone graft can allow for higher union rates by adding to the biology at the site of bone healing. Harvesting autogenous bone graft from the calcaneus for foot and ankle surgery can be done quickly and efficiently and allow for an adequate amount of graft. A retrospective chart and radiographic review was performed for 1438 patients at a single center between August 1, 2015, and December 15, 2018, who underwent calcaneal autograft harvesting using a power-driven reaming graft harvester. In total, 966 patients were included and evaluated for the safety and complication rate associated with the procedure. Only 1 patient (0.1%) had a major complication, and there were 14 minor complications (1.4%). The safety profile and low complication rate of this case series demonstrate that this simple and efficient calcaneal autograft harvest technique can be considered when a small to moderate amount of autogenous bone graft is required to augment bone healing. Therapeutic level IV, case series.

Tissue particularities and problems related to bone healing and fracture repair

Tissue particularities and problems related to bone healing and fracture repair

Assessment of Reamer Irrigator Aspirator System (RIA) filtrate for its osteoinductive potential in a validated animal model

PurposePrevious studies indicate that Reamer Irrigator Aspirator (RIA) filtrate contains proteins that have the potential to stimulate bone healing. This study aimed to determine the osteoinductive capabilities of RIA filtrate in a validated in vivo model. MethodsWith Institutional Review Board approval, RIA filtrates from 9 patients were collected. The filtrate was processed to remove cells and inorganic particles. A portion of each sample was set aside for protein analysis while the remainder was lyophilized and prepared for implantation. With Animal Care and Use Committee approval, athymic mice (n = 16; 32 hind limbs) were randomly assigned to 1 of 4 groups (n = 8 limbs per group) for percutaneous gastrocnemius muscle injection of demineralized bone matrix (DBM) (10 mg), lyophilized RIA powder (10 mg), RIA liquid (10 mg of lyophilized RIA powder in 100ul phosphate buffered saline (PBS)), or DBM (10 mg) + RIA liquid (10 mg in 100ul PBS). Radiographs were obtained 2, 4, and 8 weeks after injection. At 8 weeks, mice were sacrificed and the entire gastrocnemius muscle from each hind limb was collected and processed for histologic examination. Histological sections and radiographs were assessed for ossification/calcification. Data were compared for statistically significant (p < 0.05) differences among groups and strong (R > 0.7) correlations between outcome measures. ResultsThe protein composition of RIA filtrates was consistent among patients and matched previous data. For all groups, radiographic scores were significantly (p < 0.014) higher (more calcification/ossification) at 8 weeks compared to 2 weeks. Radiographic scores for the DBM and DBM + RIA liquid groups were significantly higher than RIA liquid and RIA powder at 4 weeks and 8 weeks (p < 0.019 and p < 0.049, respectively). Histologic scores were significantly (p = 0.004) higher in the DBM + RIA liquid group compared to the RIA liquid group at 8 weeks. Histologic scores showed strong correlations (r > 0.77) to radiographic scores for all groups. ConclusionRIA filtrate liquid and powder were osteoinductive in vivo with new bone formation being most abundant using a combination of DBM and RIA filtrate in this validated animal model. RIA filtrate has potential for clinical use in augmenting bone healing treatments.

The challenges of promoting osteogenesis in segmental bone defects and osteoporosis.

Conventional clinical management of complex bone healing scenarios continues to result in 5-10% of fractures forming non-unions. Additionally, the aging population and prevalence of osteoporosis-related fractures necessitate the further exploration of novel ways to augment osteogenesis in this special population. This review focuses on the current clinical modalities available, and the ongoing clinical and pre-clinical research to promote osteogenesis in segmental bone defects, delayed unions, and osteoporosis. In summary, animal models of fracture repair are often small animals as historically significant large animal models, like the dog, continue to gain favor as companion animals. Small rodents have well-documented limitations in comparing to fracture repair in humans, and few similarities exist. Study design, number of studies, and availability of funding continue to limit large animal studies. Osteoinduction with rhBMP-2 results in robust bone formation, although long-term quality is scrutinized due to poor bone mineral quality. PTH 1-34 is the only FDA approved osteo-anabolic treatment to prevent osteoporotic fractures. Limited to 2 years of clinical use, PTH 1-34 has further been plagued by dose-related ambiguities and inconsistent results when applied to pathologic fractures in systematic human clinical studies. There is limited animal data of PTH 1-34 applied locally to bone defects. Gene therapy continues to gain popularity among researchers to augment bone healing. Non-integrating viral vectors and targeted apoptosis of genetically modified therapeutic cells is an ongoing area of research. Finally, progenitor cell therapies and the content variation of patient-side treatments (e.g., PRP and BMAC) are being studied. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1559-1572, 2018.

Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration

Objective: Statins proved potential bone healing properties. Rosuvastatin is a synthetic, hydrophilic, potent and highly efficacious statin. In the current work, an attempt was investigated to develop, evaluate various bioerodible composite sponges enclosing rosuvastatin and explore their potential in augmenting bone healing and regeneration.Method: Twelve lyophilized sponge formulae were prepared adapting a 41.31 full factorial design. Xanthan gum, polycarbophil, Carbopol® and sodium alginate were investigated as anionic polymers, each at three chitosan:anionic polymer ratios (1:3, 1:1, 3:1). The formula of choice was implanted in fractured rat femora.Results: Visual and microscopic examination showed flexible homogenous porous structures with considerable bending ability. Polyelectrolyte complex formation was proved by DSC and FT-IR for all chitosan/anionic combinations except with xanthan gum where chitosan probably bound to the drug rather than xanthan gum. Statistical analysis proved that anionic polymer type and chitosan: polymer ratio, as well as, their interactions, exhibited significant effects on the release parameters at p ≤ 0.05. The optimum chitosan/anionic polymer complexation ratios were 3:1 for polycarbophil and 1:1 for Carbopol and alginate. The release at these ratios followed Fiction diffusion while other ratios had anomalous diffusion. Imwitor® 900K and HPMC K100M were added as release retarardants for further release optimization. The formula of choice was implanted in fractured rat femora. Histopathological examination revealed advanced stages of healing in treated femora compared to control ones.Conclusion: Biodegradable sponges for local rosuvastatin delivery proved significantly enhanced wound healing and regeneration properties to fractured bones.

Graphene and its nanostructure derivatives for use in bone tissue engineering: Recent advances.

Tissue engineering and regenerative medicine represent areas of increasing interest because of the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Graphene and its derivatives have attracted much interest for applications in bone tissue engineering. For this purpose, this review focuses on more recent advances in tissue engineering based on graphene-biomaterials from 2013 to May 2015. The purpose of this article was to give a general description of studies of nanostructured graphene derivatives for bone tissue engineering. In this review, we highlight how graphene family nanomaterials are being exploited for bone tissue engineering. Firstly, the main requirements for bone tissue engineering were discussed. Then, the mechanism by which graphene based materials promote new bone formation was explained, following which the current research status of main types of nanostructured scaffolds for bone tissue engineering was reviewed and discussed. In addition, graphene-based bioactive glass, as a potential drug/growth factor carrier, was reviewed which includes the composition-structure-drug delivery relationship and the functional effect on the tissue-stimulation properties. Also, the effect of structural and textural properties of graphene based materials on development of new biomaterials for production of bone implants and bone cements were discussed. Finally, the present review intends to provide the reader an overview of the current state of the graphene based biomaterials in bone tissue engineering, its limitations and hopes as well as the future research trends for this exciting field of science.

Do Mesenchymal Stromal Cells Influence Microscopic Residual or Metastatic Osteosarcoma in a Murine Model?

Mesenchymal stromal cells (MSCs) have been shown in rodent models to promote primary and pulmonary metastatic sarcoma growth when injected in the presence of gross tumor. In theory, this would limit their use in a clinical setting after limb salvage treatment for osteosarcoma. Although concerning, these models do not translate to the clinical setting wherein MSCs could be used after primary tumor resection to aid in bone healing and incorporation of tumor endoprostheses. If we can determine whether the use of MSCs in this setting is safe, it might improve our ability to augment bone healing in patients undergoing limb salvage. The purpose of this study was to determine (1) whether MSCs promote pulmonary metastatic disease progression in a murine osteosarcoma model; and/or (2) whether they affect local disease recurrence in the presence of microscopic residual osteosarcoma. An orthotopic model of luciferase-expressing osteosarcoma was developed. At 10 days, resection of the primary tumor was performed. One hundred fourteen female C3H mice were inoculated with DLM8-luc osteosarcoma in the proximal tibia. Ninety-four mice developed orthotopic osteosarcoma with luciferase expression. Mice with bioluminescent evidence of a primary tumor received either a microscopically "clean" amputation at a time when residual microscopic metastatic disease was present in the lungs (pulmonary metastasis group; n = 65) or a "dirty" amputation (local recurrence group; n = 29). Mice were randomized to receive intravenous MSCs, MSCs at the surgical site, or no MSCs. Mice were monitored for development and progression of pulmonary metastasis and local recurrence by bioluminescence imaging and daily measurements at the surgical site. The number of pulmonary nodules, time to first evidence of metastasis, and size of recurrent tumor were compared using Kruskal-Wallis, analysis of variance, Welch's, t-tests, or Mann-Whitney tests as appropriate for the specific data sets with p < 0.05 considered significant. Mice receiving intravenous MSCs had a faster time to first detection of pulmonary metastasis (2.93 ± 1.90 days) compared with mice with local injection of MSCs (6.94 ± 6.78 days) or no MSCs (5.93 ± 4.55 days) (p = 0.022). MSC treatment did not influence whether mice developed local recurrence (p = 0.749) or size of recurrent tumors (p = 0.221). MSCs delivered to the surgical site did not promote local recurrence or size of recurrent tumors, but intravenous injection of MSCs did hasten onset of detection of pulmonary metastatic disease. Although local administration of MSCs into a surgical site does not appear to promote either pulmonary metastatic disease or local recurrence, large variation within groups and small numbers diminished statistical power such that a Type II error cannot be ruled out. If MSCs are to be used to augment bone healing in the postlimb salvage setting in patients with osteosarcoma, it will be important to understand their influence, if any, on pulmonary micrometastsis or residual microscopic local disease. Although murine models do not completely recapitulate the clinical scenario, these results suggest that intravenous delivery of MSCs may promote micrometastatic pulmonary disease. Local administration into a surgical wound, even in the presence of residual microscopic disease, may be safe, at least in this murine model, but further investigation is warranted before considering the use of MSCs for clinical use in patients with osteosarcoma.

Bone tissue engineering using silica-based mesoporous nanobiomaterials:Recent progress.

Bone disorders are of significant concern due to increase in the median age of our population. It is in this context that tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Silica based mesostructured nanomaterials possessing pore sizes in the range 2-50 nm and surface reactive functionalities have elicited immense interest due to their exciting prospects in bone tissue engineering. In this review we describe application of silica-based mesoporous nanomaterials for bone tissue engineering. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds and composites. Also, the effect of structural and textural properties of mesoporous materials on development of new biomaterials for production of bone implants and bone cements was discussed. Also, application of different mesoporous materials on construction of manufacture 3-dimensional scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of silica-based mesoporous biomaterials on bone tissue engineering, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone.

Osteogenic differentiation of human mesenchymal stem cells in mineralized alginate matrices.

Mineralized biomaterials are promising for use in bone tissue engineering. Culturing osteogenic cells in such materials will potentially generate biological bone grafts that may even further augment bone healing. Here, we studied osteogenic differentiation of human mesenchymal stem cells (MSC) in an alginate hydrogel system where the cells were co-immobilized with alkaline phosphatase (ALP) for gradual mineralization of the microenvironment. MSC were embedded in unmodified alginate beads and alginate beads mineralized with ALP to generate a polymer/hydroxyapatite scaffold mimicking the composition of bone. The initial scaffold mineralization induced further mineralization of the beads with nanosized particles, and scanning electron micrographs demonstrated presence of collagen in the mineralized and unmineralized alginate beads cultured in osteogenic medium. Cells in both types of beads sustained high viability and metabolic activity for the duration of the study (21 days) as evaluated by live/dead staining and alamar blue assay. MSC in beads induced to differentiate in osteogenic direction expressed higher mRNA levels of osteoblast-specific genes (RUNX2, COL1AI, SP7, BGLAP) than MSC in traditional cell cultures. Furthermore, cells differentiated in beads expressed both sclerostin (SOST) and dental matrix protein-1 (DMP1), markers for late osteoblasts/osteocytes. In conclusion, Both ALP-modified and unmodified alginate beads provide an environment that enhance osteogenic differentiation compared with traditional 2D culture. Also, the ALP-modified alginate beads showed profound mineralization and thus have the potential to serve as a bone substitute in tissue engineering.

Effectiveness and Complications Associated With Recombinant Human Bone Morphogenetic Protein-2 Augmentation of Foot and Ankle Fusions and Fracture Nonunions

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been used to augment bone healing and fusion in a variety of orthopaedic conditions. However, there is a paucity of data evaluating the potential benefits of its use in foot and ankle surgery. The purpose of this study was to investigate the effectiveness and associated complications with the use of rhBMP-2 in high-risk foot and ankle fusions and fracture nonunions. A total of 51 cases in 48 patients undergoing foot and ankle fusions or fracture nonunion revisions and considered at high risk for subsequent nonunion were identified through a retrospective review in which rhBMP-2 was used as an augment for bone healing. Rate of union, time to union, and associated complications were evaluated. Forty-seven of 51 high-risk cases treated with rhBMP-2 united for a per-case union rate of 92.2%. Seventy-eight of 82 individual sites treated with rhBMP-2 united for a per-site union rate of 95.1%. Of the successful unions, the mean time to union was 111 days (95% confidence interval, 101-121). There were no statistically significant differences in time to union with regard to supplementation with bone allograft or autograft or size of rhBMP-2 kit used. Complication rates were low. rhBMP-2 was a safe and apparently effective adjunct to bony union in high-risk foot and ankle surgeries. Further randomized controlled trials are warranted. Level IV, retrospective case series.