Table 1.

Effects of hybrid of silk fibroin and collagen in cutaneous wound healing: in vitro and in vivo analysis. FTIR: Fourier transformation infrared spectroscopy.

Author	Aim	Study Design	Follow up	Findings	Conclusion
Ghezzi and co-workers (2011) [49]	To study the hybridisation of SF and dense Col for cell proliferation	In vitro	1st, 5th and 7th day	Physicochemical Characterisation -FTIR peaks at 1627 cm−1. -Absence of alteration in structural component. -High toughness. -High tensile strength. Cell–scaffold interaction -Rapid cell growth of mesenchymal stem cell (MSC). -Even distribution of cell.	-The hybrid scaffold supports the viability of human skin cells. -The dermal Col resembles ECM assisting in MSC seeding in the scaffold.
Bellas and co-workers (2012) [50]	To develop a 3D human skin equivalent using silk and Col	In vitro	Varies	Physicochemical Characterisation -Not specified Cell–scaffold interaction -Polarised morphology. -Gradual increase of Col-I and Col-IV. -The level of keratin 10 peaks on day 9. -Addition of Transforming growth factor beta (TGF-β) triggers hyper proliferation.	-3D hybrid scaffold supports all type cell proliferation in human skin.
Cui and co-workers (2013) [51]	To evaluate the efficacy of Col/SF for biocompatibility of cells	In vitro	1st, 3rd and 5th day	Physicochemical Characterisation -Scaffold dimeter depends on the SF concentration. -The average tensile strength of the scaffold was 8.7 ± 1.05 MPa when the concentration of SF at 70%. -The amide band I appears as 1646 cm−1, 1647 cm−1, 1647 cm−1, 1652 cm−1,1652 cm−1 for SF concentrations of 0%, 30%, 50%, 70%, and 100%, respectively. -The amide band II appears as 1540 cm−1 for SF concentrations of 0%, 30%, 50%, while 1541 cm−1 for SF concentrations of 70% and 100%, respectively. Cell-scaffold interaction -Proliferation of fibroblasts (L929) was at its peak by day 5. -70% of SF concentration shows greater range of cell proliferation.	-Hybrid scaffold mimics ECM; thus, it supports cell growth and proliferation.
Sun and co-workers (2014) [52]	To test the effectiveness of SF incorporated with Col for tissue engineering	In vitro	Varies	Physicochemical Characterisation -The porosity was 94.6 ± 1.1%. -Highly interconnected porous with thick wall. -The water absorption capacity was 1523.7 ± 186.6%. -Young modulus data was 49.7 ± 5.0 KPa. -High compressive characteristic. Cell–scaffold interaction -Rapid proliferation of MSC cells. -Cell infiltration was rapid at the outer surface. -Rate of cell infiltration was at 4 × 102/HP. -Visibility of cell attachment of at the inner surface.	-Hybrid scaffold suitable for tissue engineering. -Hybrid scaffold supports cell adhesion, growth, and proliferation.
Boonrungsiman and co-workers (2017) [53]	To study the effect of hybridisation of silk-based scaffold and Col type I for skin	In vitro	1st, 3rd and 7th day	Physicochemical Characterisation -Addition of Col Improves porosity and stability. -Unorganised large pores with an increase of SF. -The pore size ranges from 144.09 ± 25.97 μm to 140.67 ± 38.28 μm. -Col concentration of 7.69% and 14.89%. -Intense molecular organisation at 1071 cm−1. -Increase concentration of Col, increase the compressive modulus. -The water-absorption capacity was exceeded up to 1000% within 30 min. -Rapid degradation at day 21. -Scaffold with 0% and 3.61% of Col concentration maintains stability up to 14 days. Cell–scaffold interaction -Fibroblast adhesion was at its peak in the scaffold with 50% of Col concentration. -Transformation of round-shaped fibroblasts into spindle shaped on the first day. -Small pore size enhances cell migration. -Large pore size enhances cell attachment.	-Hybrid scaffold containing 50% of Col concentration promotes a high range of cell adhesion and the proliferation of fibroblasts.
Ramadass and co-workers (2019) [54]	To study the hybrid effectiveness of type I Col peptides and nitric oxide releasing electrospun SF scaffold in treating ischemic chronic wounds	In vitro	1st, 3rd and 5th day	Physicochemical Characterisation -Excellent porous network and void interconnection. -Addition of Col improves hydrophilicity. -No cytotoxic effect. -Presence of antibacterial property. -Nitric oxides reaches a plateau at the 12th h. Cell–scaffold interaction -Excellent adherence of NIH3T3. -Regular morphology of proliferated cell. -Accelerated proliferation of cells. -Extension and spreading of cytoskeleton.	-Hybrid scaffold is proven to be biocompatible and perfect biomaterial for ischemic wound management.
Qing and co-workers (2018) [55]	To study the outcome of porous Col/SF scaffold incorporated with zinc oxide nanoparticles in wound healing	In vivo	1st, 2nd, 4th and 8th week	Physicochemical Characterisation -Optimum size of scaffold was at 500–600 nm. -Residual at the injury site was 3.12 ± 0.02 cm2, 2.75 ± 0.14 cm2, 2.81 ± 0.53 cm2, 2.34 ± 0.12 cm2 for the first, second, fourth and eighth hour. Cell–scaffold interaction -Infiltration of inflammatory cells in the control measures. -Rapid formation of granulation tissue was at the first week. -Positive expression of interleukin. -Increased deposition of mRNA expression at the wound site. -Increased deposition of granulation tissue. -Reduced inflammatory cells at the wound site. -On the 4th week, epidermal tissue exhibits a compact structure. -Rapid reepithelisation at the injury site.	-Hybrid scaffold increases the rate of healing by decreasing the inflammatory response.
Cui and co-workers (2020) [32]	To study the hybrid effectiveness of tussah SF and Col loaded with mesenchymal stem cell for wound healing.	In vivo	1st, 7th, 14th, 21st and 28th day	Physicochemical Characterisation -Porosity ranges from 81% to 84%. -Water absorption capacity was >96%. -WVTR ranges from 52% to 64%. -Scaffold that has been freeze-dried shows positive interconnection and porous morphology. -Degradation occurs at 330 °C and 345 °C. -Scaffold porosity increase proportional to the Col level. -Water vapor transmission rate (WVTR) inversely proportional to Col content. Cell–scaffold interaction -60% of cell successfully adhere to the scaffold. -The rate of cell viability increases with the increase of Col concentration.	-Hybrid scaffold promotes the maturation of blood vessels and accelerates wound healing.
Kim and co-workers (2013) [56]	To study the efficacy of human Col and silkworm gland hydrolysate (SSGH) for wound healing	In vitro and in vivo	3rd, 7th, 10th and 15th day	Physicochemical Characterisation -The porosity ranges from 61% to 81%. -Increased ratio of SSGH decreases the stability of the scaffold. -Greatest protein release was seen at 1:1 and 1:0 ratio of SSGH. Cell–scaffold interaction -Disappearance of debris. -Rapid re-epithelisation. -Rapid expansion of tissue. -Rapid migration of fibroblasts. -Absence of cytotoxicity at SSGH concentration at 0.01 g/mL to 1 g/mL.	-Hybrid scaffold enhance rapid healing from day 10 until day 15.
Wu and co-workers (2019) [57]	To study the efficiency of produced nanofibrous mat comprising of (SF)/polycaprolactone (PCL) electrospun with chitosan and Col type I in treating dermal wound and formation of scar	In vitro and In vivo	3rd, 7th and 14th day	Physico-chemical Characterisation -Increased mechanical strength. -Increased hydrophilic property. -Increased porosity. -Major XRD peak at 21.8°. -High crystallinity structure. -Rough surface -Good binding ability of the nanofibrous mat. Cell–scaffold interaction -Increased cell adhesion in cell counting kit-8 (CCK-8) assay. -Rapid cell attachment, growth, and proliferation. -Increased production of Col. -Reduced in wound-closure timing. -Reduced scar formation. -Decreased wound-healing time. -Reduced in wound exudation. -Reduced inflammation.	-Hybrid scaffold promotes blood capillary distribution. -Complete wound healing achieved at day 14 day.