Table 2.

Biological scaffolds

Scaffold	Case	Duration	Trial	Results	Complications	Reference
Collagen scaffold	Long bone non-unions (group rhBMP-7 n = 60 group PRP) n = 60)	> 9 months	The purpose of this prospective randomized clinical study was to compare the efficacy of rhBMP-7 and PRP as bone-stimulating agents in the treatment of persistent fracture non-unions.	Both clinical and radiological union occurred in 52 (86.7%) cases of the rhBMP-7 group compared to 41 (68.3%) cases of the PRP group, with a lower median clinical and radiographic healing time observed in the rhBMP-7 group.	Complications including severe, moderate and mild; adverse events were classified as serious or non-serious	Calori et al. [31]
Porous collagen I scaffold	Volumetric bone deficiencies (n = 10)	3 years	The clinical outcomes of ten patients with volumetric bone deficiencies treated with MSCs and bone marrow aspirate are presented in this case series. Results were evaluated with radiographs.	All patients showed bony healing and/or sufficient new bone formation within follow-up. There were no restrictions to any physical activities prior to the causative disease at latest follow-up. All patients returned to their profession after treatment.	1 prolonged hematoma	Jager et al. [18]
Absorbable collagen sponge scaffold	Open tibial fractures (n = 450)	12 months	The objective of this study was to evaluate the safety and efficacy of the use of rhBMP-2. 450 patients with an open tibial fracture were randomized to receive either the standard of care, the standard of care and an implant containing 0.75 mg/mL of rhBMP-2, or the standard of care and an implant containing 1.50 mg/mL of rhBMP-2. The rhBMP-2 implant (rhBMP-2 applied to an absorbable collagen sponge) was placed over the fracture at the time of definitive wound closure.	The rhBMP-2 implant was safe and, when 1.50 mg/mL was used, significantly superior to the standard of care in reducing the frequency of secondary interventions and the overall invasiveness of the procedures, accelerating fracture and wound-healing, and reducing the infection rate in patients with an open fracture of the tibia.	Local adverse events including inflammation, infection, hardware failure, pain, and complications.	Govender et al. [19]
Absorbable collagen sponge scaffold	Open tibial fractures (n = 510)	12 months	The objective of the current study was to perform a subgroup analysis of the combined data from these studies. 510 patients were randomized to receive the control treatment or the control treatment and an absorbable collagen sponge impregnated with one of two concentrations of rhBMP-2. The rhBMP-2 implant was placed over the fracture at the time of definitive wound closure.	The addition of rhBMP-2 to the treatment of type-III open tibial fractures can significantly reduce the frequency of bone-grafting procedures and other secondary interventions. This analysis establishes the clinical efficacy of rhBMP-2 combined with an absorbable collagen sponge implant for the treatment of these severe fractures	NC	Swiontkowski et al. [20]
Collagen sponge and Hap scaffold	Volumetric bone deficiencies patients (n = 39) with collagen scaffold (n = 12) and HA scaffold(n = 27)	> 6 months	The study investigated the potency of BMAC to augment bone grafting and support bone healing. The functional and radiographic outcome of 39 patients with treated with BMAC are presented and evaluated	All patients showed new bone formation in radiographs during follow-up. Two patients underwent revision surgery due to a lack in bone healing. The postoperative bone formation and complete bone healing appeared earlier in the HA group in contrast to the Collagen group.	1 persisting hematoma, 3 wound secretions	Jager et al. [32]
Gel foam scaffold	16 patients (n = 51 ribs) who underwent costectomy with gel foam scaffold and 15 patients (n = 33 ribs) with no scaffold.	6 months	The aim of the study is to compare rib regeneration with a scaffold placed intra-periosteally against no scaffold, after costectomy in adolescent idiopathic scoliosis. Patients were analyzed radiographically for rib regeneration and morphology.	The resulting data showed that majority of ribs re-grew to normal morphology in 3–6 months in the trial group. Ribs treated by placement of gel foam scaffold regenerate to a near normal radiological profile within 6 months of costectomy compared to a slower regeneration in those without gel foam scaffold.	NC	Philip et al. [35]
Complex cellular scaffold	Post-traumatic nature bone defects (n = 8)	6–8 weeks	Critical size defects were treated with the IM technique. Morphological characteristics, cell composition, and growth factor expression were compared with healthy diaphyseal P. Functional and molecular evaluation of MSC activity was performed.	Both tissues shared similar morphology although IM was significantly thicker than P. The IM resembles periosteum with a cellular composition and molecular profile facilitating large defect repair and therefore may be described as an “induced-periosteum”	NC	Cuthbert et al. [33]
Intra-operative cellular bone substitution material scaffold	Various bone healing disturbances (n = 101)	2-24 months	The objective of the study was to evaluate new bone formation after the application of BMAC as well as to record complications. The application of BMAC was performed via a local injection as part of a core decompression (n = 72) or by the local adsorption of intra-operative cellular bone substitution material (scaffold) incubated with BMAC during osteosynthesis (n = 17)or in further surgery (n = 12).	Only 2 patients were observed complications. Infections, excessive new bone formation, induction of tumor formation and morbidity due to the bone marrow aspiration from the iliac crest were not seen.	2 complications	Hendrich et al. [34]