Table 3.

Synthetic scaffolds

Scaffold	Case (n = sample)	Duration	Trial	Results	Complications	Reference
HAp	Bone tumors (n = 3)	29–43 months	MSCs obtained from each patient’s bone marrow cells were forced to differentiate into osteoblasts followed by bone matrix formation on HAp ceramics to heal bone tumors using tissue-engineered implants. Serial plain radiographs and computed tomography images were used to observe results.	The strong osteogenic ability of the implants, as evidenced by high osteoblastic activity, was confirmed. The tissue-engineered HAp was used to fill the patient’s bone cavity after tumor curettage. Immediate healing potential was found and no adverse reactions were noted in these patients	NC	Morishita et al. [36]
Porous HAp ceramic scaffold	Large bone diaphysis defects (n = 4)	6.5 years	Cells from the patients’ bone marrow stroma were expanded in culture and seeded onto porous HAp ceramic scaffolds designed to match the bone deficit in terms of size and shape. Conventional radiographs and CT scans evaluated patients.	No major complications occurred in the early or late postoperative periods. No signs of pain, swelling, or infection were observed at the implantation site. Complete fusion between the implant and the host bone occurred 5 to 7 months after surgery.	No major complications and No signs of pain, swelling, or infection.	Marcacci et al. [37]
HAp	Large bone defects (n = 3)	> 15 months	Osteoprogenitor cells were isolated from bone marrow and expanded ex vivo. These cells were placed on macroporous hydroxyapatite scaffolds and implanted at the lesion sites. External fixation was provided initially for mechanical stability and was subsequently removed.	In all three patients, radiographs and computed tomographic scans revealed abundant callus formation along the implants and good integration at the interfaces with the host bones by the second month after surgery.	NC	Quarto et al. [38]
IP-CHA	22 patients (n = 30 hips) who used BMMNCs with IP-CHA and 8 patients (n = 9 hips) with cell-free IP-CHA of osteonecrosis of the femoral head	> 12 months	We have investigated the effectiveness of the transplantation of BMMNCs and cell-free with IP-CHA on early bone repair for osteonecrosis of the femoral head.	In the BMMNC group, a reduction in the size of the osteonecrotic lesion was observed subsequent to hypertrophy of the bone in the transition zone and three patients were detected extensive collapse. In the control group, severe collapse of the femoral head occurred in six of eight hips.	No intra- or post-operative complications	Yamasaki et al. [39]
HAp/type I collagen composite scaffold	Bone defects by benign bone tumors with HAp/Col (n = 63) and β-TCP (n = 63)	18 and 24 weeks	The efficacy and safety of HAp/Col were assessed in comparison β-TCP. X-ray images and blood tests and observation of the surgical site were performed to evaluate the efficacy and safety of the implants.	The highest grade of bone regeneration was more frequent in the porous HAp/Col group than in the porous β-TCP group (p = 0.0004 and 0.0254 respectively). The incidence of adverse effects was higher in the porous HAp/Col group than in the β-TCP group.	NC	Sotome et al. [40]
HAp/TCP scaffold	Spondylolisthesis (n = 25)	12–27 months	Autograft/ TSRH pedicle screw instrumentation (n = 5), rhBMP-2/TSRH (n = 11), and rhBMP-2 only without internal fixation (n = 9). On each side, 20 mg of rhBMP-2 was delivered on a carrier consisting of 60% HAp and 40% TCP granules (10 cm3/side).	RhBMP-2 with the biphasic CaPs granules induced radiographic posterolateral lumbar spine fusion with or without internal fixation in patients whose spondylolisthesis did not exceed grade 1. Statistically greater and quicker improvement in patient-derived clinical outcome was measured in the rhBMP-2 groups.	No complications	Boden et al. [41]
rCPBS scaffold	Recalcitrant tibial fracture nonunion (n = 20)	14 ± 2.7 months	All patients were treated with a procedure including debridement and decortications of the bone ends, nonunion fixation with a locking plate, and filling of the bony defect with a combined graft of rhBMP-7 (as osteoinductor) with an rCPBS (as scaffold)	No specific complication of rCPBS or rhBMP-7 was encountered. The application of rCPBS combined with rhBMP-7, without any bone grafting, is safe and efficient in the treatment of recalcitrant bone union.	No specific complication	Ollivier et al. [43]
β-TCP scaffold	Femoral defects with autologous MSC/ β-TCP (n = 9) and β-TCP (n = 9)	12 months	Compare healing quality of implantation into femoral defects during revision total hip arthroplasty, containing either expanded autologous MSC (trial group) or Β-phosphate alone (control group).	A significant difference in the bone defect healing was observed between both groups of patients (p < 0.05). Trabecular remodeling was found in all nine patients in the trial group, and only 1 patient in the control group.	2 dislocation and 1 pulmonary embolism, and 1 cardiac arrhythmia	Sponer et al. [42]
Bonelike scaffold	Medial compartment osteoarthritis of the knee (n = 11)	12 months	The aim of the present work was to assess the biological behavior of Bonelike graft and osteoconductive properties and resorption characteristics of the granulesin. Radiological follow-up, scanning electron microscopy, histological analysis and histomorphometric measurements were conducted on the retrieved samples to assess bone regeneration in the defect area.	Bonelike acted as an excellent bioactive scaffold, allowing the migration, proliferation, and differentiation of bone cells on its surface, and therefore regeneration of the defects was achieved in a rapid, controlled manner.	NC	Gutierres et al. [47]
BoneSave (TCP/HAp)	Posterolateral inter-transverse spinal defects(n = 45)	46 months	Analogue scales for pain, patient global impression of change, work status, persisting symptoms and patient satisfaction data, radiological evaluation of fusion was carried out from the most recent spinal radiographs available for each patient	Significant post-operative improvements were seen across all outcome measures in the large majority of cases. Successful fusion was achieved in 56.7% of cases.	Avoid donor site morbidity	Kapur et al. [44]
BoneSave (TCP/HAp)	34 patients received uncemented acetabular components (n = 34) and 9 received cemented components (n = 9)	2 years	BoneSave using mixtures of allograft and BoneSave in impaction grafting were used to assess the effectiveness.	There were no re-revisions and there was no implant migration. Complications were rare (1 fracture, 2 dislocations). Impaction grafting of BoneSave and allograft is an effective method of dealing with loss of bone stock at revision hip surgery in short-term study.	1 fracture, 2 dislocations	Blom et al. [46]
BoneSave (TCP/HAp)	34 patients received uncemented acetabular components (n = 34) and 9 received cemented components (n = 9)	7 years	Patients were followed up radiographically and with the SAPS, OHS, and SF12 health survey. Kaplan-Meier survivorship analysis was performed with revision of the acetabular component, revision of any part of the construct, and reoperation as endpoints.	1 patient had been revised for aseptic loosening of the acetabulum and 1 for deep infection. BoneSave is a reliable material for impaction grafting of the acetabulum when used in conjunction with femoral head allograft in medium-term study.	NC	Whitehouse et al. [45]